: Pediatr Nephrol (2006) 21:1493–1635 # IPNA 2006 DOI 10.1007/s00467-006-0236-x

ABSTRACTS

UNCORRECTED PROOF 1494 Pediatr Nephrol (2006) 21:1493–1635 Pediatr Nephrol (2006) 21:1493–1635 1495 1496 Pediatr Nephrol (2006) 21:1493–1635 Pediatr Nephrol (2006) 21:1493–1635 1497 1498 Pediatr Nephrol (2006) 21:1493–1635 Pediatr Nephrol (2006) 21:1493–1635 1499 1500 Pediatr Nephrol (2006) 21:1493–1635

CONTENTS

Oral Communication OC 11 Acute renal failure OC 1 Bladder disorders and voiding disturbances OC 12 - OC 13 Bone, growth and mineral metabolism OC 14 - OC 16 Chronic renal failure OC 5 - OC 6 Clinical nephrology OC 3 - OC 4 Glomerular disease OC 20 Hemodialysis OC 8 Hereditary renal disease OC 9 - OC 10 Hypertension OC 19 Peritoneal dialysis OC 17 - OC 18 Transplantation OC 7 Tubular and interstitial disorders OC 2 Urinary tract infection and VUR

Oral Poster OP 31 - OP 33 Acute renal failure OP 11 Bladder disorders and voiding disturbances OP 55 Bone, growth and mineral metabolism OP 52 - OP 54 Chronic renal failure OP 12 - OP 17 Clinical nephrology OP 4 - OP 1O Experimental nephrology OP 41 - OP 49 Glomerular disease OP 38 - OP 40 Hereditary renal disease OP 51 Hypertension OP 1 - OP 3 Kidney development and cell biology OP 30 Obstructive urophathy OP 56 - OP 60 Peritoneal dialysis OP 21 - OP 29 Transplantation OP 34 - OP 35 Tubular and interstitial disorders OP 50 Urinary mineral abnormalities and urolithiasis OP 18 - OP 20 Urinary tract infection and VUR OP 36 - OP 37 Vasculitis and autoimmune related disease Pediatr Nephrol (2006) 21:1493–1635 1501

Poster Presentation PP 116 - PP 122 Acute renal failure PP 71 - PP 76 Bladder disorders and voiding disturbances PP 300 - PP 312 Bone, growth and mineral metabolism

PP 313 - PP 342 Chronic renal failure PP 20 - PP 70 Clinical nephrology PP 10 Electrolyte and fluids PP 1 - PP 9 Experimental nephrology PP 343 - PP 393 Glomerular disease PP 102 - PP 115 Hemodialysis PP 159 - PP 196 Hereditary renal disease PP 277 - PP 299 Hypertension PP 11 - PP 16 Kidney development and cell biology PP 146 - PP 158 Obstructive urophathy PP 394 - PP 413 Peritoneal dialysis PP 17 - PP 19 Renal pysiology PP 197 - PP 246 Transplantation PP 123 - PP 145 Tubular and interstitial disorders PP 264 - PP 276 Urinary mineral abnormalities and urolithiasis PP 77 - PP 101 Urinary tract infection and VUR PP 247 - PP 263 Vasculitis and autoimmune related disease 1502 Pediatr Nephrol (2006) 21:1493–1635

COD. OC 1 COD. OC 2 ULTRASOUND BLADDER MEASUREMENTS CAN REPLACE Uneffectiveness of antibiotic prophylaxis in children with VUR. URODYNAMIC STUDY FOR DIAGNOSIS OF NON- Preliminary data from a controlled study. MONOSYMPTOMATIC NOCTURNAL ENURESIS Pennesi M, Peratoner L*, Giacomini A, Travan L, Bordugo A*, Minisini S Clinica L TAFURO, D DEL GAIZO, M VERNI`, L R IERVOLINO, R DEL GADO Pediatrica-IRCCS Burlo Garofolo-Trieste *Pediatria-Ospedale S.M. degli Angeli- DEPARTMENT OF PEDIATRICS, SECOND UNIVERSITY OF NAPLES , via L. De Pordenone Presenting Author: Pennesi Marco Crecchio , 80131 Napoli , Italy IRCCS Burlo Garofolo , via dell`Istria 65/1 , 34100 Trieste , Italy

Purpose: we have compared urodynamic studies (UD) with ultrasound (US) measurements Background: Antibiotic prophylaxis in VUR affected children has never proved to be for diagnosis and follow-up of patients with Non-Monosymptomatic Nocturnal Enuresis effective in preventing recurrent urinary infections and secondary renal damage. (NMNE). Objective: To determine the efficacy of antibiotic prophylaxis in reducing UTI and Methods: 738 enuretics children with daytime voiding symptoms have been subordinated to secondary renal damage in VUR affected children. UD and to US bladder. The upper limits for US bladder wall thickness measurements are 3 Methods: 100 children diagnosed with grade 2 to 4 mono/bilateral VUR were enroled in the and 5 mm (full and empty bladder). 704 children (95,4%) have urodynamic signs of a study and have been randomized in two groups (prophylaxis versus non prophylaxis). overactive bladder and the US bladder wall measurements thickened. After a six-month At the entry of the study all children underwent to renal scan with dimercaptosuccinic acid antimuscarin treatment, we have repeated a new study with US and UD. Also after the first (DMSA) done at least 4 months after the UTI. cycle of therapy we have confirmed relation between urodynamic and ultrasound The children in the prophylaxis group were administered a two years antibiotic treatment. measurements. Basing on this evidence, we have modified diagnostic management of The DMSA and VCUG has been repeted after 2 years. patients with NMNE. In enuretics with daytime voiding symptoms and with significant US Results: 90 patients, (43 treated, 47 not treated) completed two years of follow up. measurement (bladder wall thickness >3mm and >5mm to full and empty bladder Total relapses has been 61 in 29 patients;36 in 16 children in the prophylaxis group vs 25 respectively) diagnostic management is concluded. This new protocol has been applied to among 13 children in the control group (0.3 relapses/year/patient). 296 patients with NMNE. Only 11 cases had a worsening in the DMSA scan: 2 border line at the entry became grade I After the first 6 months of therapy, a new US study has been performed in all patients. without UTI; 9 pathologic at the entry, 5 worsened without UTI and 4 with 1 or 2 UTI. Results: we found that 224 patients (75,7%) were full-responders with normal detrusor On the contrary in all the other cases with one or more UTI, we did not find any DMSA thickness; 54 patients (18,2%) were partial responders but without normalization of detrusor scan worsening. thickness; only 18 patients (6,1%) were classified as non-responders with a persistence of a Conclusions: thickened bladder wall. The UTI relapses have been more common n the children treated with antibiotic Conclusions:. According to our experience US, which is non-invasive, is especially useful prophylaxis. for diagnosis and follow-up of NMNE instead of UD, which is invasive and often traumatic There are no evidence of any relationship between the number of UTI relapses and the for children. progression of the renal damage.

COD. OC 3 COD. OC 4 Glomerular sclerosis in kidneys with congenital nephrotic syndrome Nephrin is critical for the action of insulin on human glomerular (NPHS1) podocytes A-M Kuusniemi, A Kaukinen, A-T Lahdenkari, C Holmberg, R Karikoski, and H Jalanko RJM Coward , GI Welsh, A Koziell, J Tava ré, P W Mathieson, M A Saleem Hospital for Children and Adolescents and Biomedicum Helsinki, University of Helsinki, Bristol children`s hospital and Academic renal unit , Department of clinical sciences, North Finland Bristol, Southmead hospital, , BS10 5NB Bristol , UK , Biomedicum Helsinki, Haartmaninkatu 8, huone B526b , 00290 Helsinki , Finland The leading causes of albuminuria and end stage renal failure in the world are secondary to Congenital nephrotic syndrome of the Finnish type (NPHS1) is caused by mutations in the abnormalities in the production or cellular action of insulin including diabetes mellitus and NPHS1 gene encoding podocyte slit diaphragm protein nephrin. Children with NPHS1 have the hyperinsulinaemic metabolic syndrome. The human glomerular podocyte is a critical severe nephrotic syndrome from birth and are nephrectomized as infants. The removed cell for maintaining the filtration barrier of the kidney and preventing albuminuria. We have kidneys serve as a unique human material to analyze the development of renal failure in recently shown this cell to be insulin sensitive in respect to glucose uptake with kinetics kidneys with proteinuria. In this work, the histology and expression of glomerular cell similar to muscle cells1. We now show that the podocyte protein nephrin is essential for this markers and cytokines were studied in nephrectomized NPHS1 kidneys using light and process in podocytes. Unique conditionally immortalised podocytes from two different electron microscopy, immunohistochemistry, Western blotting, and cytokine array. The patients with nephrin mutations (natural human nephrin knockout models) are unresponsive results showed that mesangial sclerosis and obliteration of capillaries were evident in to insulin, knocking nephrin down with siRNA in wild type podocytes abrogates the insulin practically every glomerulus (1530 glomeruli studied). Severely damaged and well response and stable nephrin transfection of nephrin deficient podocytes rescues their insulin preserved nephrons were commonly found adjacent to each other. Several profibrotic response. Mechanistically the c terminus of nephrin is forming a protein-protein interaction mediators and enzymes were expressed in NPHS1 glomeruli. Few inflammatory cells with the vesicular SNARE protein VAMP2 (using yeast-2 hybrid studies and co- (NPHS1: 3.71.8 vs. controls: 1.10.2 cells/glomerular cross section (GCS); P<0.05) were immunoprecipitation) which functionally allows the GLUT1 and GLUT4 rich vesicles to detected in the glomeruli in spite of the increased expression of several chemokines. The fuse with the membrane of this cell. This work demonstrates a previously unsuspected role podocytes showed severe ultrastructural changes and hypertrophy but little hyperplasia of nephrin in vesicular docking and insulin responsiveness of podocytes. (MIB-1: 0.15/GCS in NPHS1 vs. 0.03/GCS in controls) or apoptosis (TUNEL: 0/GCS vs. 0.06/GCS). Moderate amounts (median 15.9 cells/ml vs. 0.7 cells/ml; P<0.05) of podocytes 1Coward et al. The Human Glomerular Podocyte Is a Novel Target for Insulin Action. were secreted into the urine of NPHS1 patients. No crescents, tip lesions or misdirected Diabetes 54:3095-3102. filtration into paraglomerular or paratubular space were detected. In conclusion, the results indicate that podocyte damage in NPHS1 kidneys lead to endocapillary lesions that progress to glomerular sclerosis. Glomerular tuft adhesions, crescent formation and misdirected filtration seem to play a minor role in this process. Pediatr Nephrol (2006) 21:1493–1635 1503

COD. OC 5 COD. OC 6 Efficacy of Levamisole as a Single Agent in Maintaining Remission in Assessing renal function in obese children – based on weight, height or Steroid Dependant Nephrotic Syndrome what? 1. AS Abeyagunawardena 2. RS Trompeter 1.Department of Paediatrics, University of J Feber, N Dust, S Hadjiyannakis, G Filler Peradeniya, Sri Lanka 2.Nephrology Unit, Great Ormond Street Children’s Hospital, Dept.of Pediatrics, Children`s Hospital of Eastern Ontario , 401 Smyth Rd. , K1H8L1 London, UK Ottawa , Ontario Canada , 155, George E de Silva Mawatha , A155 Kandy , Sri Lanka Background: The growing pandemic of childhood obesity results in cardiovascular and Levamisole ( LEV ) originally developed as an anti helminthic and renal complications, which require assessment of renal function. Commonly used GFR subsequently shown to have immunomodulatory properties has been used formulas with variables including serum creatinine (Scr), height (H) and weight (W) or successfully in conjunction with low dose alternate day prednisolone in steroid dependant body surface area may yield false results in obese patients. nephrotic syndrome (SDNS). This randomised controlled carried out between 2002 and Methods: Body mass index z-scores were derived from the US National Center for Health 2005 at a single centre in Sri Lanka to evaluate the efficacy of LEV as a single agent Statistics 2000. GFR (ml/min/1.73 m2) was estimated by Schwartz formula (GFR = (H x following a prolonged period of combination therapy of LEV + prednisolone. k) / Scr; with k=49.9 for adolescent males and 46.2 for all other patients, KI 2005;67:2321), cystatin C (log(GFR) = 1.962 + [1.123 * log (1/Cystatin C)]), BCCH1 (based on W and H) Sequential Children with SDNS in stable remission who had been treated with LEV + low and BCCH2 (based on age only) equations (JASN 2006;17:487). Parametric or non- dose alternate day prednisolone ( 0.1-0.6mg/kg ) for 2 years were randomised to one of two parametric tests based on distribution were used for statistical analysis. groups. The test group received LEV (2.5 mg/kg) on alternate days for one year and the Results: We compared the 4 GFR estimates in 59 patients (mean age of 13.2±3.0 years, control group received no treatment. Urine protein excretion was performed and recorded mean BMI z-score 5.34±2.89). Median Schwartz GFR (129.9, range 90-190) and BCCH1 by parents on daily basis and the finding of 3+ proteinuria for three consecutive days was (122.4, range 82-201) were significantly greater when compared to the CysC-GFR (106.5, diagnostic of relapse. range 69-151) and BCCH2 (108.6, range 55-147), both p<0.001, Wilcoxon’s matched pai r test. There was no significant difference between BCCH2 and Cystatin C GFR. There were 42 in the test group ( mean age 8.4 years) and 34 in the control group ( mean Conclusion: GFR formulas including weight and height consistently yield higher GFR age 7.2 years). During one year of follow up 26/34 in the control group and 8/42 in the test values in obese patients than cystatin C GFR and/or GFR equations based on age only. group suffered a relapse. (p < 0.001 comparison of 2 proportions using Standard Error. CI 0.105 to 0.49). No adverse effects were encountered.

The estimated cost of treatment with LEV for one year for a child weighing 20kg is less than 30 euros per year. LEV is therefore safe, affordable and effective as a single agent in maintaining remission in SDNS.

COD. OC 7 COD. OC 8 BLUNTED ACUTE RESPONSE TO HYDROCHLOROTHIAZIDE IN PHENOTYPE-GENOTYPE CORRELATIONS IN A COHORT OF 72 GITELMAN SYNDROME FŒTUS AND NEONATAL DEMISE PATIENTS WITH A Bettinelli* (Presenting Author), G Colussi,° M L Syrèn**, N Borsa°°, S Tedeschi°°, C AUTOSOMAL RECESSIVE POLYCYSTIC KIDNEY DISEASE Mattiello°° and M G Bianchetti^ Department of *Pediatrics of Merate (Italy) and (ARPKD) ^Bellinzona (Switzeland) and °Nephrology of Varese; **Department of Pediatrics and C Loirat1, A Bourillon2, O Pascaud1, B Gerard1, AL Delezoide1, R Bouvier3, MC Neonatology, University of Milan and **Laboratory of Medical Genetics, IRCCS Gubler4, L Michel-Calemard5, P. Missy1, I Zaccaria1, H Le Nagard1, CAlberti1, E Policlinico, Milan, Italy. Denamur1. 1 Hôpital Robert Debré, AP-HP, Paris. 2 Hôpital Bichat, AP-HP, Paris. 3 Department of Pediatrics , Mandic Hospital , 23807 Merate , Lecco Italy Hôpital Edouard Herriot, Lyon. 4 Inserm U574, Paris. 5 Hôpital Debrousse, Lyon. France. Hôpital Robert Debré , 48 bd Sérurier , 75019 Paris , France Introduction. Gitelman syndrome results from inactivating mutations in the thiazide- sensitive sodium-chloride cotransporter gene. Unfortunately, the molecular diagnosis of this We analysed the correlation between the severity of renal and hepatic histological lesions disease is cumbersome. It has been suggested that in this disease the effect of and PKHD1 mutations in 72 cases of ARPKD detected prenatally (54 foetus (median hydrochlorothiazide on urinary chloride and sodium excretion is blunted and diagnostic. gestational age (GA) 28 w), 18 new-borns (median age at death :1 day). Renal lesions Study design. The acute effect of hydrochlorothiazide (mean dose, 1 mg/kg) was studied in e 16 pediatric and 23 adult patients with at least one mutation in the sodium-chloride severity was correlated with GA ( 30 w vs > 30 w : p = 0.04). Hepatic fibrosis also tended cotransporter gene and in 11 healthy control subjects. The diuretic effect was evaluated to be more severe for GA > 30 w (NS). The 66 coding exons of PKHD1 were studied using according to Colussi G (Am J Nephrol, 1997) as the net difference between the highest direct sequencing. Among the 144 alleles, 119 mutations were identified (83 %), including individual clearance value after hydrochlorothiazide and the mean of the two basal 63 truncating (stop or frameshift) mutations (53 %), 47 missense mutations (39,5 %), of clearances (Delta FE Clmax and Delta FE Namax, %). which 20 were possibly damaging and 27 possibly benign (www.bork.embl- Results. Delta FeCl max had a median value of 1.01% (range – 0.30 +2.22%) and 1.10% heidelberg.de/polyphen), 6 splice mutations (5 %), 2 in-frame insertions/deletions, 1 (range +0.25 +3.60%) in pediatric and adult Gitelman patients, respectively. In control abolition of the STOP codon. 72 different mutations were identified, 46 of them (64 %) subject it was 3.48% (+2.29 +5.36%). Delta Fe Namax demonstrated a median value of unreported. No mutations were found in only 2 cases. Three mutations were recurrent: 0.08% (-0.36 +1.64%) and 0.75% (+0.25 +2.36%) in pediatric and adult Gitelman patients, T36M (14), c.9689delA (12) and c.5895dupA (9). Thus, screening of 6 exons (3, 14, 32, 36, respectively. It was 2.40% (+1.47 +4.23%) in control subjects. The effect on urinary 57, 58) allowed the identification of 43,8 % of mutations. We categorized mutations as potassium excretion was similar in patients and controls. severe (S) (truncating, possibly damaging missense, or splice mutation) or other than S, and Conclusions. The effect of hydrochlorothiazide on urinary chloride and sodium excretion is genotypes as S/S (29) or non S/S (43). S/S genotypes were correlated with more severe blunted in patients with Gitelman syndrome. It is therefore assumed that a blunted response renal lesions than non S/S, for similar GA (p = 0.04). The correlation with hepatic fibrosis to hydrochlorothiazide further supports the diagnosis of Gitelman syndrome in subjects with severity was NS. clinical and biochemical findings consistent with the diagnosis of this syndrome. In conclusion, this cohort allowed us to identify a set of PKHD1 mutations associated with severe renal lesions. 1504 Pediatr Nephrol (2006) 21:1493–1635

COD. OC 9 COD. OC 10 REDUCED KIDNEY VOLUME IN PRETERMS BUT NO EFFECT Oxydative stress and arterial injury in adolescents with primary ON RENAL FUNCTION AT SCHOOL AGE hypertension A Rakow L Legnevall S Johansson G Celci M Norman H Lagercrantz M Vanpee M Litwin, J Sladowska, A Wierzbicka, E. Skorupa, A Niemirska, ZT Wawer, J , Department of Women and Child Health, Karolinska Institutet, Stockholm, Sweden , Antoniewicz 17176 Stockholm , Sweden The Children`s Memorial Health Institute , Dept. of Nephrology & Arterial Hypertension , 04-730 Warsaw , Poland Background: Poor early growth resulting in fewer nephrons and impaired renal function is a proposed mechanism for adult hypertension (Brenner et al). We investigated whether renal The main risk factors of intima-media thickening (IMT) are systolic and pulse pressure, function and volume is associated with gestational age and /or birthweight in school age dyslipidemia and hyperhomocysteinemia. The injury of arterial wall may lead to oxidative children. stress (sox) and sox may by itself perpetuate arterial wall injury. The aim of the study was Methods: Children born between 1990-93 were allocated to three groups: Born before to test hypothesis that children with primary hypertension (PH) are exposed to greater sox gestational week 30(Preterm, n=39), born term but small for gestational age (SGA, n=29) and that markers of sox correlate with IMT and metabolic risk factors of arteriosclerosis. and born term with normal weight (Control,n=37). Renal function was estimated by Study design: controlled, cross-sectional. Patients: 78 children with untreated PH, aged 14.7 calculating creatinine clearence using the Schwartz formula and by measuring urinary yrs (5-20), 23 girls and 55 boys. Controls: 83 healthy children aged 13.4 yrs (4-23), 44 girls protein patterns, N-acetylglucosamin (U-NAG), albumin, immunglobulin (Ig-G) and alpha- and 39 boys. Methods: assessment of IMT in common carotid (cIMT) and superficial 1-microglobulin (U-A1M). Volumetric ultrasound of the kidneys was performed in 86 femoral arteries (fIMT). Sox was assessed as plasma glutathione (GSH), GPX peroxidase children (Preterm, n=33;SGA, n=25; Control,n=28). (GSX) and thiobarbituric acid reactive substances (TBARS). Results: PH pts had greater Results: Kidney volume,ml, was significantly lower in preterms and SGA compared to BMI (p <0.05) , blood pressure (p < 0.05), cIMT (p<0.05), carotid wall cross sectional area Control adjusted for body mass index (80.8 +/- 3.2 and 81.5 +/- 3.7 versus 90.8 +/- 3.4, (WCSA) (p<0.05), fIMT (p<0.05) and lower HDL-cholesterol, and apoA1/apoB than p=0.02, mean +/- SE). Creatinine clearence, ml/min/1.73m2, was not different between the control group (p<0.05). GSH and GPX did not differ between groups but TBARS was groups (Preterm: 89.6 +/- 2.3; SGA: 88.8 +/- 2.5 and Control: 88.3 +/- 2.1, p=0.92, mean significantly greater in PH pts (p = 0.03). In control group fIMT significantly correlated +/- SE). Urinary protein patterns were similar between the groups (all p-values >/= 0.15). with CRP (p = 0.003, r=0.302), homocysteine (p = 0.02, r = 0.240), apoA1 (p=0.03, r=- Conclusion: Children born with low birth weight have smaller kidneys at 11-14 years of age 0.217), GPX (p=0.018, r=-0.241) and TBARS (p=0.002, r=0.329). cIMT did not correlate which might be due to fewer nephrons. However, this does not lead to renal impairment at with sox markers. In pts group, there were similar correlations between CRP, dyslipidemia this age. and fIMT but TBARS were significantly correlated with cIMT (p=0.0001, r=-0.429), WCSA (p=0.0001, r=-0.391) and fIMT (p=0.04, r=-0.232). Conclusions: PH pts are exposed to significantly higher sox but markers of arterial injury are negatively correlated with TBARS. The significant correlations between markers of oxidative stress and biochemical parameters suggest that vascular injury is an effect of interplay between oxidative stress, metabolic and hemodynamic insults.

COD. OC 11 COD. OC 12 NEONATAL VASOMOTOR NEPHROPATHY: A LONG TERM 1,25-Dihydroxyvitamin D3 increases the expression of Calbindin D9k FOLLOW-UP STUDY and TRPV6 in uremic rat aortas and primary rat vascular smooth E Allain-Launay (1), G Roussey-Kesler (1), JL Orsonneau (2), C Guyot (1), JC Roze (3), muscle cells JM Liet (3) (1) Clinique médicale pédiatrique, CHU Nantes, France (2) Service de Hong Zebger-Gonga b, Dominik Müller a,b, Kerstin Sommer a,b, Kai König a,b, Dieter biochimie, CHU Nantes, France (3) Réanimation pédiatrique, CHU Nantes, France Haffner a,b, Berthold Hocher b, Michaela Diercke a,b, Sven Schmidt c, Uwe Querfeld a,b a , Hopital de jour pédiatrique, Hopital Mère-Enfant, Quai Moncousu , 44093 cedex 1 Department of Pediatric Nephrology, Campus Virchow-Klinikum, b Center for Nantes , France Cardiovascular Research, Campus Charité Mitte, c Department of Nephrology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Berlin, Germany Objective: To describe long-term renal outcome of neonatal vasomotor nephropathy. Charité Universitätsmedizin Berlin , Campus Virchow , 13353 Berlin , German y Germany Methods : 227 new-borns older than 2 days with acute renal failure (ARF), defined as serum creatinine > 130µmol/L for at least 48 hours, were retrospectively selected from a Vitamin D may contribute to cardiovascular disease in patients with chronic kidney disease. biochemical prospective data bank of 11,178 infants hospitalized in a neonatal intensive We have previously observed vascular calcifications in uremic rat aortas treated with 1,25 care unit from 1995 to 2004. Among the 108 survivors, 98 had an ARF related to a (OH)2D3 in the absence of hypercalcemia, indicating that 1,25(OH)2D3 may have direct vasomotor nephropathy. During 2005, they were invited to have renal investigations. effects on calcium transport of vascular smooth muscle cells, resulting in deposition of Results : Mean term and birth weight of the 98 newborns were 31± 5 weeks , and 1630 ± calcium in the vascular wall. Target proteins affecting cellular calcium transport in the 1040 g. Mean neonatal ARF duration was 15 ± 10 days. 18% of the patients had a kidney include the calcium binding protein Calbindin D9k and the calcium channel TRPV6. creatininemia higher than 50µmol/L at discharge. The purpose of this study was to investigate whether Calbindin D9k and TRPV6 are Fifty-eight out of the 98 children had long term examinations at a mean age of 6 ± 2.6 involved in the development of vascular calcification. years. Six (10%) had a glomerular filtration rate (GFR) lower than 80mL/min/1.73m². The incidence of reduced GFR was significantly influenced by the duration of neonatal ARF (25 Uremia was established in Sprague-Dawley rats by 5/6 nephrectomy. Animals were treated vs 14 days, p<0.05) and by creatininemia at discharge (64 vs 37 µmol/L, p< 0.05). Urine with 0.25 ng/kg/d of 1,25(OH)2D3 or vehicle for 6 weeks. Primary vascular smooth muscle protein/creatinine ratio was normal for all. Microalbuminuria (available in 16 children) was cells (VSMC) were obtained from thoracic aortas of Wistar-Kyoto rats and incubated for 24 high in 4 cases. One child received medication for hypertension. Tubular reabsorption of hr with 1,25(OH)2D3 at different concentrations. Protein expression was investigated by phosphate was decreased in 7, particularly in patients with low GFR (80,1% vs 89,6%, Immunostaning (TRPV6 and Calbindin D9k). PCR products were first sequenced to verify p<0.001). correct amplification the target genes.followed by qRT-PCR (Taqman). Conclusion : Newborns with vasomotor nephropathy are at risk of substantial nephronic reduction. Larger prospective studies are needed to address long-term renal outcome in this the aortic expression of Calbindin D9k and TRPV6 in 1,25(OH)2D3–treated uremic rats population. was significantly increased compared with untreated uremic controls. Moreover, 10-7 M of 1,25(OH)2D3 markedly increased the expression of Calbindin D9k and TRPV6 in VSMCs.

These data suggest that 1,25(OH)2D3 induces the upregulation of Calbindin D9k and TRPV6 in rat VSMCs (in vitro) and in the arterial wall of uremic rats (in vivo). The definite role of these two prime targets of 1,25(OH)2D3 has to be elucidated in further studies. Pediatr Nephrol (2006) 21:1493–1635 1505

COD. OC 13 COD. OC 14 BONE CONDITION IN PEDIATRIC RENAL TRANSPLANT Parathyroid hormone level and the dose of calcitriol therapy relate to RECIPIENT (PRTR): EVALUATI ON WITH QUANTITATIVE arterial structure and coronary calcification in children on dialysis ULTRASOUND R Shroff1, AE Donald2, M Hiorns3, A Watson4, S Feather5, D Milford6, EA Ellins2, C A Mussa (1) F Porta (2) B Gianoglio (3) M Gaido (3) R Camilla (3) F De Terlizzi (4) A Storry2, J Deanfield2, L Rees1 Nephrourology Unit1, Radiology Department3 and Vascular Amore (3) Prsenting author: A Mussa (1) 1.Department of Pediatric Endocrinology, Regina Physiology Unit2 Great Ormond Street Hospital NHS Trust and Institute of Child Health, Margherita Children Hospital, Torino, Italy 2.I Pediatric Clinic, University of Torino, Italy London, UK. 4Children and Young People’s Renal Unit, Nottingham City Hospital, 3.Department of Pediatric Nephrology, Regina Margherita Children Hospital, Torino, Italy Nottingham, UK. 5St James’s University Hospital, Leeds, UK. 6Birmingham Children’s 4.IGEA biophysics laboratory, Carpi (MO), Italy C de Sanctis(1) R Coppo (3) Hospital, Birmingham, UK. Regina Margherita Childrens` Hospital , Dept Pediatric Nephrology , 10126 Torino , Italy Great Ormond Street Hospital for Children NHS Trust , Vascular Physiology Unit, 34 Great Ormond Street , WC1N 3JH London , UK UK Pediatric renal transplant recipient (PRTR) are at risk of bone impairment caused mainly by hyperparathyroidism and glucocorticoid (GCS) therapy. Phalangeal Quantitative Ultrasound Background Phenotypic changes in conduit arteries are described in dialysis patients and are (QUS) is a radiation-free technique that allows assessment of bone quality through velocity linked with cardiovascular mortality, but there are few studies in children that describe their of the ultrasound (AD-SoS) and time of transmission through bone (BTT), parameters determinants. directly connected to bone density and cortical thickness; these parameters give insight about mineralization by the comparison with normal values of healthy population matched Methods Patients aged 5–18 years on dialysis forQ 6 months and in CKD Stage IV forQ 3 for age (Z-score). years were recruited from 4 centres. Calcium[Ca], phosphate[PO4], intact-PTH ([iPTH], Phalangeal QUS, seric calcium, phosphate, intact parathormone (iPTH) were performed on expressed as multiples of the upper limit of normal[ULN]), doses of phosphate-binders and 40 PRTR (25 males, mean age 20,0±8,4, range 4,3-34,4) at 7,1±3,8 years from calcitriol were recorded from stage IV CKD. Patients were divided into: Group I, median transplantation. Cumulative dosage of GCS and cyclosporine was calculated for each iPTH < twice ULN (n=41); and Group II, iPTH > twice ULN (n=44). Groups were matched patient. for confounders and compared to age-matched controls (n=33). High-resolution carotid Mean Z-scores for AD-SoS and BTT were respectively -0,05±1,59 and -0,54±1,17; the least artery ultrasound for intima-media thickness (IMT), applanation tonometry for aortic pulse- was significantly below normal values (p=0,001). In 5(12,5%) patients bone mineral density wave velocity (PWV) and helical CT scan for cardiac calcification were performed. was decreased, in 11 (27,5%) was in lower part of normal range. Patients with increased Results IMT in Group I was comparable to controls(0.39mm vs 0.38mm,p=0.44) and lower iPTH (n=29) had decreased Z-scores if compared to patients with normal iPTH (p=0,007). than in Group II (=0.58mm,p<0.0001). IMT increased with increasing PO4 levels Patients with previous rejection episodes had lower Z-scores than patients without (p<0.0001) and CaxPO4 product (p<0.001). Aortic PWV correlated with PO4 (p=0.03), but rejections (p=0,026). Multivariate analysis showed AD-SoS Z-scores significantly not with iPTH (p=0.5). The odds of developing cardiac calcification were 2.3 times greater dependent on iPTH, GCS in first year after transplant, and cyclosporine assumption; BTT in Group II than in Group I. Six in Group II had moderate-severe calcification (score >100) Z-scores were dependent on GCS in first year after transplant and age. compared to 1 child in Group I. The youngest patient with cardiac calcification was 5.8 In conclusion, QUS revealed impaired bone condition in PRTR; subject with previous years old. Elemental-Ca intake from PO4-binders was unrelated to vascular parameters but rejection episodes or with high iPTH showed greater compromise. Immunosuppressant calcitriol correlated with IMT (p<0.001) and cardiac calcification score (p<0.02). On dosage appeared important determinant in bone condition, in particular glucocorticoids multiple regression analysis PTH, PO4 and calcitriol dose were independent predictors of dosage during first year after transplantation appeared to be the most important factor. IMT, and PTH and calcitriol were significant predictors of cardiac calcification. Conclusion Maintaining the PTH level within twice the ULN and using the lowest possible dose of calcitriol reduced vascular damage in children on dialysis, which may be of prognostic importance.

COD. OC 15 COD. OC 16 The effect of ketoanalog essential aminoacid supplementation and low- LONG-TERM DISSOCIATION OF ANTIPROTEINURIC AND protein diet on chronic renal failure in childhood ANTIHYPERTENSIVE EFFICACY OF ACE INHIBITION IN I Haszon, V Sümegi, É Gombos, Zs Györke, K Meichelbeck, E Molnár, L Szabó, M Vissy, CHILDREN WITH CHRONIC RENAL FAILURE STúri E Wuehl O Mehls F Schaefer for the ESCAPE TRIAL Group , University of Szeged, Korányi fasor 14-15 , H-6720 Szeged , Hungary University Children`s Hospital, INF 150 , Division of Pediatric Nephrology , 69120 Heidelberg , Germany Background: Ketoanalog aminoacids (KAs) on a low-protein diet (LPD) were associated with a delay in the progression of chronic renal failure (CRF), reduction in proteinuria and The ESCAPE Trial evaluates the renoprotective efficacy of constant ACE-inhibition with they help to preserve the nutritional status. In childhood CRF there is small number of data ramipril (6 mg/m²/d) in children with CRF. In 100 children receiving ramipril for 3 years published about KAs diet. Methods: A long term, retrospective study was made with the 24h-mean arterial pressure was persistently reduced from +1.2 to -0.1, -0.1, -0.3, and -0.2 collaboration of five Hungarian Pediatric Nephrology Centers. 38 CRF (group I) and 22 SDS after 0.5, 1, 2, and 3 years, respectively. The mean protein/creatinine-ratio decreased CRF patients on haemodialysis (group II) were enrolled. They were given LPD (0.8-1.0 from 1.0 mg/mg at baseline to 0.46 after 6 months treatment (p<0.0001). However, g/day protein intake) supplemented with KAs. The control group consisted of 20 CRF proteinuria increased again during ongoing treatment and reached the baseline level at the patients on LPD (group III). end of the third treatment year (mean 0.87 mg/mg). The initial drop in proteinuria was The average therapeutic time was 43.3+20.3 month in group I, 43.0+25.3 month in group II, positively correlated with baseline proteinuria and negatively with GFR. The rebound of and 24.0+16.9 month in group III. During the study the serum levels of urea, creatinine (S- proteinuria was independent of age, GFR, blood pressure and rate of CRF-progression prior Cr), total protein, albumin, calcium and phosphorus were measured. The endogenous to and under ramipril treatment. Out of 78 patients with an initial proteinuria reduction, a creatinine clearance was calculated according to the Swartz formula. The progression of the rebound during ongoing treatment by >50 % of the initial drop was observed only in 1 of 9 CRF was calculated with the linear regression of S-Cr-1. Results: The progression of the with glomerular but in 35/69 with hypo-dysplastic disorders. In the actuarial survival CRF was slower in group I than in the controls and also slower than it is suggested in the analysis of the total ESCAPE cohort (400 pts), ongoing proteinuria (>150 mg/m²/d) during literature (Schmicker, 1986). The nutritional stage did not change in group I and II during ramipril treatment was associated with a significantly poorer renal survival, whereas the study. In contrast to group III, the serum phosphate level didn’t elevated in group I. baseline proteinuria was not predictive. Conclusions: KAs supplementation on LPD effectively reduces the progression of CRF and In summary, a partial loss of the antiproteinuric efficacy is observed during long-term ACE- prevents hyperphosphatemia in CRF children. The height and weight gain was adequate, inhibition in many children with chronic renal failure. This effect is dissociated from a their nutritional stage was unchanged. persistently good blood pressure control, and may compromise the long-term nephroprotective action of ACE-inhibition. Concepts of intensified ACE-inhibition o r additional blockade of the angiotensin-receptor should be evaluated in these patients. 1506 Pediatr Nephrol (2006) 21:1493–1635

COD. OC 17 COD. OC 18 An open, prospective, randomised, controlled, multi-centre study CMV infection under calcineurin inhibitor / prednisone and basiliximab comparing Fixed Dose vs. Concentration Controlled mycophenolate induction therapy in pediatric renal transplant recipients mofetil regimens for de novo patients following renal transplantation B Kranz, U Vester, A-M Wingen, S Nadalin, A Paul, PF Hoye r (the FDCC trial) Pediatric Nephrology, University Essen/Germany , Clinic for Pediatric Nephrology, Burkhard Tönshoff, on behalf of the FDCC investigators University Children’s Hospital, Hufelandstrasse 55 , 45122 Essen , Germany Heidelberg, Germany. University Chiildren`s Hospital , Im Neuenheimer Feld 150 , D-69120 Heidelberg , Newer immunosuppressive drugs (basiliximab, MMF) are reported to be associated with Germany better graft survival. The incidence of cytomegalovirus(CMV) infection under these immunosuppressive regimens is of concern and was reported with an incidence up to 40% Introduction. Several studies have shown a relationship between MPA plasm a (Jungraithmayr2003). concentrations and the likelihood of acute rejection after renal transplantation (rtx). A To evaluate the incidence of CMV infection in children after kidney/liver-kidney randomized trial comparing Fixed Dose (FD) with Concentration Controlled (CC) MMF transplantation under a restrictive immunosuppression (basiliximab, calcineurin-inhibitor, dosing (FDCC trial) was therefore designed to study prospectively the contribution of prednisone) and a prospective CMV monitoring. The incidence of CMV infection after add therapeutic drug monitoring to MMF efficacy. Methods. 901 de novo rtx patients (62 on of MMF in a subgroup was analysed. pediatric) from 65 centers in 19 countries were randomized 1:1 to either FD or CC MMF 104 children (mean age 10.6±5.3, follow up 4.1±2.3 years) receiving consecutive 109 therapy with calcineurin inhibitors and corticosteroids. In the CC group, abbreviated AUCs kidney or liver-kidney (n=11) transplants were analysed. Primary immunosuppression: (C0, C30min, C2hrs) on day 3, day 10, week 4 and months 3, 6 and 12 were used to adjust basiliximab (n=103), cyclosporine A (n=96) or tacrolimus (n=13) and prednisone. MMF the MMF dose to reach a target MPA-AUC0-12 between 30 and 60 mg/L*hr. Results. was added in 23 patients during the first year for various reasons beside acute rejection. Pediatric patients were evenly distributed over the CC (n=31) and FD group (n=31), over CMV infection was defined as the positive detection of pp65, CMV disease as clinical the CNI comedication (Tac, n=40, 47.5% in FD, 52.5% in CC; CsA, n=22, 54.5% in FD, manifestations. Prophylactic CMV immunoglobulin was given to 30 R-/D+recipients. 45.5% in CC) and over induction therapy (80% in CC, 84% in FD). The incidence of CMV infection was detected in 22(20.1%) patients 1.5±1.0 months after transplantation. biopsy-proven acute rejection (BPAR) was 5/31 (16.1%) in CC vs. 2/31 (6.5%) in FD (p = 9/22(40.1%) had CMV disease. Acute biopsy proven rejections within the first year 0.19), although the proportion of patients on day 3 and 10 with an AUC0-12 below target happened in 25/87(28.7%) transplants without CMV and 7/22(31.2%) after a CMV was lower in CC (21%) than in FD (40%). Conclusion. These preliminary data show that infection (p=0.08). In 6/23(26.1%) patients treated with MMF CMV infection was detected MMF dose adjustments based on a limited number of abbreviated AUCs were not able to (odds ratio 1.4) with 4/6(66.7%) showing CMV disease (odds ratio 2.1). Kaplan Meyer reduce the incidence of BPAR at 6 months in pediatric renal transplant recipients. At ESPN analysis revealed CMV constellation R-/D+ (p<0.0001) and D+serostatus (p=0.0001) to be 12 month outcome data will be available. significantly associated with CMV infection. In this cohort the add on therapy with MMF seems to be associated with a higher incidence of CMV diseases. It has to be discussed whether this may be acceptable with projected graft survival.

COD. OC 19 COD. OC 20 Gram-negative peritonitis in children on chronic peritoneal dialysis. Impact of daily hemodialysis in children on statural growth Report for the International Pediatric Peritonitis Registry. M Fischbach,C Dheu,J Terzic,S Menouer, F Schaefer,A Zurowska,R Feneberg,M Monteverde, J Misselwitz, M Kemper, B Acar, M , Nephrology Dialysis Transplantation Children’s Unit, University Hospital Hautepierre, Zimmering, B Warady for the IPPR. University Children`s Hospital, Heidelberg, Germany Avenue Molière67098 Strasbourg, France , 67098 strasbourg , france France Gdansk University Medical School, Poland University Children`s Hospital, Heidelberg, Germany Hospital de Pediatria, Buenos Aires, Argentina F Schiller University, Jena, Linear growth disorder remains a common problem in hemodialysed children : more Germany University Hospital, Freiburg, Germany Gazi University School of frequent dialysis might improve outcome. We determined linear growth in five consecutive Medicine,Ankara, Turkey Charite, Humbolt University, Berlin, Germany Children`s Mercy children on in center daily hemodialysis (Dd), mean age 8 years 7 months at enrolement ; Hospital, Kansas City, USA 4/5 were on growth hormone for a mean of 28.5 months before Dd. Dd was delivered 5 to 6 Department Pediatric Nephrology , Gdansk University Medical School , 80-211 Gdansk , times weekly, three hours each session. Mean follow up of Dd was 18.6 months. Dropout Poland from Dd was kidney transplantation (n=4) or transfer to another center (n=1). Dd and free diet improved appetite, thereby protein intake was above 2 g/kg/BW. Mean weekly Objective: to determine the clinical presentation, response to treatment and outcome of Kt/Vurea was 9.1±0.4. Calcium phosphorus product were kept in normal range without gram-negative peritonitis in children need for phosphate chelators in 4/5 cases. During conventional dialysis ht SDS decreased Patients and methods: 122 episodes of gram-negative peritonitis (24%) were reported to the from -0.8 to –1.44, which occurred predominantly before rhGH start, conducting patients to IPPR out of a total 548 episodes from children on chronic peritoneal dialysis in Europe, –1.62 ht SDS. Conversion to Dd increased growth velocity to a mean of 13 cm/year (10.3- Asia and the Americas. The patients were treated according to ISPD guidelines with 18) with a mean change of +1.84 ht SDS/year (0.4 to 2.7). This preliminary report suggests ceftazidime and cefazolin or a glycopeptide. the potential efficacy of a Dd regimen in promising growth velocity, either directly to a Results: The clinical manifestation of peritonitis was uniform for all gram-negative higher dialysis dose or indirectly through an improved nutritional status. organisms (Pseudomonas 21%, Klebsiella 18%, E.coli 17%). Severe abdominal pain, elevated temperature (mean 37.9±0.9), marked fluid cloudiness, a high cell count (mean 2177 ± 2653 cells/µl) with predominant PMN (85 ± 15%) were typical. Antibiotic prophylaxis and causative organism grown at exit site (ES) were recognized as predisposing factors for pseudomonas and upward ES orientation for E.coli infections. In spite of the high initial response rate a change in antibiotic therapy was performed in 46 patients (38%).By multivariate analysis a single cuff catheter, severe abdominal pain and intermittent ceftazidime were independent predictors of a poor initial response. Final full recovery was achieved in 85% of episodes regardless of the organism involved. 19 patients required catheter exchange (16%), 11 relapsed (9%). Exit site infection (OR 0.089 p=0.013), lack of improvement at day 3 (OR 0.111 p=0.0021) and age<2 years (OR 0.200 p=0.018) were independent risk factors for not achieving full recovery by multivariate analysis. Exit site infection (OR 12.95 p=0.006) and severity of symptoms at onset (OR 2.203 p=0.009) were independent predictors of catheter removal. Pediatr Nephrol (2006) 21:1493–1635 1507

COD. OP 1 COD. OP 2 Anomalies of TCF2 (HNF-1béta) is the main cause of foetal bilateral MUTATIONALANALYSIS OF THE ÇÏ×Á11 AND HOXD11 hyperechogenic kidneys GENES IN CHILDREN WITH CONGENITAL ANOMALIES OF S Decramer, F Bandin, O Parant, C Guillou, S Kessler, J Aziza, C Bellanné-Chantelot THE KIDNEY AND URINARY TRACT Paediatic Nephrology , 330,av de grande bretagne , 31059 toulouse cedex9 , France I Bouba1, E Siomou2, CJ Stefanidis3, Á Emmanouilidou1, F Papadopoulou4, Ì Syrrou5, É Georgiou1, Á Siamopoulou-Mavridou2 Laboratory of Human Reproductive Genetics, Prenatal discovery of foetal bilateral hyperechogenic kidneys is very stressful for pregnant Medical School, University of Ioannina1, Department of Pediatrics, University Hospital of women. Accurate prenatal diagnosis will allow better acceptance and a tailor-made follow- Ioannina2, Department of Nephrology «P. & Á. Kyriakou» Children’s Hospital, Athens3, up of the infants. Hepatocyte nuclear factor (HNF)-1 encoded by the TCF2 gene is Department of Radiology, University Hospital of Ioannina4, Laboratory of General involved in the embryonic development of the kidneys. Mutations of TCF2 gene are known Biology, Medical School, University of Ioannina5 , Greece to be responsible for the maturity onset diabetes of the young type 5 and various adult , EMMANOUIL XANTHOU 58 , 45445 IOANNINA , Greece nephropathies. We studied 57 pregnancies with foetal bilateral hyperechogenic kidneys. Quantitative Congenital anomalies of the kidney and urinary tract (CAKUT) constitute the major cause multiplex PCR amplification of short fluorescent fragments for the search of large genomic of chronic renal failure in infants and young children. The homeobox genes (HOX) have arrangements and sequencing for the detection of point mutations were sequentially been suggested to play a key role in the development of the kidney and urinary tract. Gene- performed in 20 children. Pre and postnatal ultrasound, renal and extrarenal data were target studies in experimental mouse models have shown that the genes Hoxa11/Hoxd11 are analyzed. essential for kidney development and specifically for the epithelial differentiation of the TCF2 anomalies were detected in 14 patients (24%) and characterized by a complete metanephric mesenchyme. Hoxa11/Hoxd11 double mutants demonstrate renal agenesis or heterozygous deletion of the TCF2 gene in 13/14. Family screening revealed de novo TCF2 hypoplasia. anomalies in 6 probands. TCF2 anomalies were associated with normal amniotic fluid Because to our knowledge these genes have never been examined for alterations in humans, volume (14/14) and normal kidney size except in two sisters. Antenatal cysts were detected we evaluated whether mutations of HOXA11/HOXD11 are associated with CAKUT and in only 8/14 patients. Among patients with cysts the predominant ultrasound phenotype is specifically with renal agenesis and hypoplasia/dysplasia in humans. cortical cysts a multicystic kidney. After birth, cysts appeared during the first yea r DNA samples from 18 children with unilateral renal agenesis and 19 children with severe (13/14) and in patients with antenatal cysts the number increased and developed bilaterally renal hypoplasia/dysplasia where included in this study. Exons 1 and 2 of the HOXA11 and with a decreased renal growth. Renal function decreased with longer follow-up and was HOXD11 genes were amplified individually by PCR using 12 unique overlapping lower in patients with solitary kidney. oligonucleotide primers. SSCP analysis of the PCR products was performed. Heterozygous deletion of TCF2 is an important etiology of foetal hyperechogenic kidneys. SSCP analysis revealed no variant band shifts in the samples of the amplified segments of The variable postnatal evolution imposes a prospective long term follow-up. the 37 patients, suggesting lack of either mutation or polymorphisms. Our findings do not support the suggestion that mutations in the HOXA11/HOXD11 genes are involved in the pathogenesis of renal agenesis or dysplasia/hypoplasia. A functional overlap of the HOX genes of the 11th paralogous group in various systems and organs has been shown, suggesting that other genes of this group could be implicated in the development of these phenotypes.

COD. OP 3 COD. OP 4 A mechanism underlying how acquired focal segmental INSULIN-LIKE GROWTH FACTOR-1 (IGF-1) IMPROVES THE glomerulosclerosis is caused by disruption of plasma homeostatic HYPOXEMIA-INDUCED ACUTE RENAL VASOMOTOR factors NEPHROPATHY IN THE NEWBORN RABBIT. R Lennon1, D Trouet3, RR Foster1, L Ni1, RJ Coward1, DO Bates2, J Eggermont3, PW A Prévot 1,2, D Mosig 1, M Julita 1, DK Tung 1 and JP Guignard 1. 1 Department of Mathieson1, MA Saleem1 1Academic and Children’s Renal Unit, University of Bristol, Pediatrics, Renal Unit, CHUV, 1011 Lausanne. Switzerland. 2 Department of United Kingdom. 2Microvascular Research Laboratories, Department of Physiology, Medicine/Physiology, 1700 Fribourg. Switzerland. Presenting Author: A P révot University of Bristol, United Kingdom; 3Laboratory of Physiology, University of Leuven, University of Fribourg , Department of Medicine/Physiology , 1700 FRIBOURG , Leuven, Belgium. Switzerland Academic Renal Unit, Lifeline Centre , Southmead Hospital , BS16 1AE Bristol , UK In animal models and humans, acute normocapnic hypoxemia induces functional renal Acquired FSGS is a disease of the glomerular podocyte, resulting in massive proteinuria, insufficiency by increasing the renal vascular resistance (RVR), leading to renal and the pathogenesis is attributed to unexplained disorders of circulating plasma. Recently hypoperfusion and decreased GFR. In humans and normoxemic adult animal models, acute inappropriate activation of the calcium channel TRPC6 was causally linked to familial IGF-1 administration induces pre- and postglomerular vasodilation, thereby increasing RBF FSGS. We report a functional link between TRPC6, nephrin and human plasma, which and GFR. In newborns, IGF-1 activity is low and further decreases during hypoxia. provides an explanation for the pathogenesis of acquired FSGS based on the presence of Therefore, the present study was designed to assess a potential protective effect of IGF-1 on essential circulating homeostatic factors. hypoxemia-induced acute renal failure in newborn rabbits. Methods: Human conditionally immortalised podocytes (wild type (WT), nephrin mutant Renal function (including inulin and PAH clearances) and hemodynamic parameters were (FM) and FM rescued by stable transfection with nephrin (FM-N)) were used. TRPC6 assessed in 17 anaesthetized and mechanically-ventilated newborn rabbits (5-9 d-old) activity was measured by stimulation with OAG/Flufenamate. undergoing a hypoxemic stress for 3 hours and given an iv bolus of saline (time control) or Results: Activation of TRPC6 in WT podocytes was abrogated by exposure to human IGF-1 (1 mg/kg). plasma (HPL). In FM cells, TRPC6 activity remained high in HPL, and the HPL Normocapnic hypoxemia significantly increased RVR (+18%), leading to a decrease in suppressive effect was rescued in FM-N podocytes. Furthermore, RhoA was activated in the GFR (-14%), RBF (-21%) and diuresis (-12%). An increase in filtration fraction (FF) presence of fetal calf serum (FCS) and suppressed by HPL. Inhibition of RhoA in WT cells indicated a preferential hypoxemia-induced efferent vasoconstriction. While saline did not relocalised nephrin to the cell surface and suppressed TRPC6 activity. Finally plasma from preclude further deleterious effects of hypoxemia seen over time, IGF-1 administration four consecutive FSGS patients in post-renal transplant relapse activated TRPC6 compared prevented a further increase in RVR (+18% vs +59% with saline), with subsequent to paired remission plasma and this effect was reversible by RhoA inhibition. improvement in GFR (-16% vs -38%), RBF (-18% vs -45%) and diuresis. FF returned to Conclusion: We provide evidence that factors in normal human plasma inhibit RhoA, control normoxemic values, suggesting relative postglomerular vasodilation induced by leading to nephrin localisation at the cell surface, where it inhibits TRPC6 activity. These IGF-1, supposedly through nitric oxide and/or prostaglandins activation. factors are absent or inhibited in recurrent FSGS. To our knowledge, this is the first human Although the hypoxemia-induced acute vasomotor nephropathy could not be totally disease reported, to be caused by such a disturbance of normal plasma homeostatic factors. prevented by IGF-1, this agent induced efferent vasodilation, thereby blunting the vasoconstrictive effect of an acute hypoxemic stress.

Supported by a grant from the Swiss National Science Foundation (3200-064041.00). 1508 Pediatr Nephrol (2006) 21:1493–1635

COD. OP 5 COD. OP 6 URINARY PROTEOME OF STEROID-SENSITIVE AND STEROID- Therapeutic effect of neutralining endogenous IL-18 activity in the RESISTANT IDIOPATHIC NEPHROTIC SYNDROME OF adrimycin-induced model of minimal-change nephritic syndrome CHILDHOOD C Shanlin and X Linsheng Presenting Author: C Shanlin RP Woroniecki, TN Orlova, IF Shatat N Mendelev, FJ Kaskel,MS Goligorsky, E Guiyang Medical College , Department of Pediatrics , 550004 Guiyang , Guizhou Province O’Riordan. China Albert Einstein College of Medicine, Children`s Hospital at Montefiore , Department of Pediatric Nephrology 111 East 210th Street , 10467 Bronx , New York USA The etiology of minimal-change nephritic syndrome (MCNS) is poorly understood. It has been proposed that interleukin(IL)-18 may act as a key effect molecule involved in the The response to steroid therapy is used to characterize the idiopathic nephrotic syndrome pathogenesis of MCNS. We report herein that ardrimycin(ADR)-induced model of MCNS (INS) of childhood as either steroid sensitive (SSNS) or steroid resistant (SRNS), a in mice is inhibeted by treatment with anti-IL-18 antibody (IL-18AB). MCNS was induced classification with a better prognostic ability than renal biopsy. The majority (~80%) of INS in 16 mice by single injection of ADR (7.5mg/kg). The mice were then treated with PBS (n((n(( is due to minimal change disease but the percentage of focal and segmental = 8) or with IL-18AB(0.5mg/kg, n = 8) on days 5,7,12, and 21 after ADR administration.on. glomerulosclerosis is increasing. We applied a new technological platform to examine the The protein in urine were measured on day 1,7,14,28,42.The serum total protein (((( Tp), urine proteome to determine if different urinary protein excretion profiles could albumin(Ab),cholesterol(Ch), triglyceride(Tg),and serum IL-18, IFN-r, TNF-á IL-4 were differentiate patients with SSNS from those with SRNS. measured, and renal pathological changes were examed at 6th week by electron microscopy Twenty-five patients with INS and 17 control patients were studied. Midstream urines were when mice were sacrificed. Results showed that all ADR-mice developed nephropathy analyzed using surface enhanced laser desorption and ionization mass spectrometry characterized by proteinuria, hypoalbuminaemia and hyperlipydaemia. Overt proteinuria (SELDI-MS). Data were analyzed using multiple bioinformatic techniques. Patient appeared at day 7 and remained significantly elevated throughout the study period. classification was performed using Biomarker Pattern Softwareä and a generalized form of Ultrastructural analysis showed widespread fusion of foot processes of glomerular epithelial Adaboost. cells and swelling of mitochondrion. The production of IFN-ã, TNF-á and IL-18 in ADR- Urinary proteomic data distinguished INS patients from control patients, irrespective of mice were markedly increased in comparison with control mice injected with salin instead steroid response, with a sensitivity of 92.3%, specificity of 93.7%, positive predictive value of ADR. However, the significantly reduced proteinuria, an increase in serum Tp, Ab and a of 96% and a negative predictive value of 88.2%. Classification of patients as SSNS or decrease in serum Ch, Tg were observed in ADR-mice treated with IL-18AB as compared SRNS was 100%. A protein of mass 4144Da was identified as the single most importan t to placebo treated ADR-mice. Ultrastructural determination revealed only focal and classifier in distinguishing SSNS from SRNS. significantly reduced fusion of foot processes of the glomerular epithelial cells in IL-18AB SELDI-MS combined with bioinformatics can identify different proteomic patterns in INS. treated ADR-mice. Treatment with IL-18AB led to significant decreased production of IL- Characterization of the proteins of interest identified by this proteomic approach with 18, IFN-ã and TNF-á in ADR-mice. prospective clinical validation may yield a valuable clinical tool for the non-invasive Conclusion IL-18AB may inhibit both clinical and histological changes in the ADR-induced prediction of treatment response and prognosis. MCNS. This inhibition correlated with reduced production of IL-18,IFN-ã and TNF-á, suggesting a shift of Th1 immune response.

COD. OP 7 COD. OP 8 IGFBP-2 overexpression enhances focal-segmental glomerulosclerosis in Beneficial Effect Of Triple Trea tment (ACEI, AT1RB, statin) Plus GH transgenic mice by induction of Hic-5 in podocytes Immunoglobulin in Experimental Nephrotic Syndrome J. Oh1, S. Moeglich1, M. Hoemme1, T. Fisch2, P. Mundel4, B. Schuett3, A. Hoeflich2, E. S Akman 1*, S Kalay 1, B Akkaya 2, M Koyun 1, H Akbas 3, YE Baysal 1, M Gultekin 3, Wolf2, R. Wanke2, B. Tönshoff1 1University Children’s Hospital Heidelberg, 2Institute of A Gur Guven 1 1Department of Pediatric Nephrology, Akdeniz University, Medical Molecular Animal Breeding and Biotechnology/Gene Center, Munich, 3University Faculty, Antalya, Turkey 2Department of Pathology, Akdeniz University, Medical Faculty, Children’s Hospital Tübingen, Germany, 4Mount Sinai School of Medicine, New York, Antalya, Turkey 3Department of Biochemistry, Akdeniz University, Medical Faculty, USA Antalya, Turkey University Childrens Hospital , INF 150 , 69120 Heidelberg , Germany , Akdeniz University, Medical Faculty, Department of Pediatric Nephrology , 07070 Antalya , Turkey Background: A hallmark of glomerular proteinuria is podocyte foot process efface-ment due to enhanced cell migration. Because insulin-like growth factor-2 (IGFBP-2) enhances cell Combination of antiproteinurics including inhibitors of the angiotensin I-converting enzyme mobility in several tumour cells through an IGF-independent mecha-nism and plasma (ACEI) or AT1 receptor blockers(AT1RB) and statins is a hopeful choice in the treatment IGFBP-2 is markedly elevated in the nephrotic syndrome, we inves-tigated the effect of of steroid resistant nephrotic syndrome(SRNS). We aimed to investigate the effects of high- IGFBP-2 overexpression in a mice model of FSGS. Results: He-mizygous CMV-promoter dose immunoglobuline in addition to these combinations in experimental nephrotic IGFBP-2 transgenic mice were crossed with hemizygous PEPCK-promoter GH transgenic syndrome. mice, generating 4 genetic groups of offspring: mice carrying both transgenes, a single The study included 40 rats in five groups of control, nephrotic syndrome without treatment mIGFBP-2 or bGH transgene, and non-transgenic controls. While isolated IGFBP-2 (NS), dual therapy(DT) by enalapril(50 mg/L)&losartan(200 mg/L), triple therapy(TT) by overexpression did not demonstrate a renal pheno-type, GH transgenics had pronounced enalapril&losartan &simvastatin(10 mg/kg) and quadruple therapy(QT) by enalapril& glomerular sclerosis and proteinuria; this phe-notype was aggravated 2-fold in mice losartan&simvastatin&immunoglobuline(2 gr/kg). All of the rats except the control group carrying transgenes for both GH and IGFBP-2. By immunohistochemistry, Hic-5, a TGF- were given adriamycin at a dose of 2 mg/kg of body weight at the first day and at the third inducible protein, showed enhanced stain-ing in podocytes of double transgenic mice and to week. Blood samples were drawn from non-fasting rats and 24-h urine samples were a lesser extent in single GH trans-genics compared to control and IGFBP-2 transgenics. In collected on day 1 and at weeks5, 8, 12, and 16. cultured immortalized podo-cytes, 125I-IGFBP-2 specifically bound to cells via 51- At the 5th week, urinary protein excretions in the groups of NS, DT, TT and QT were integrin. Exogenous IGFBP-2 stimulated Hic-5 protein expression in cultured podocytes in significantly higher and serum albumin levels were lower than the control group in after a dose-dependent man-ner via a signalling pathway involving focal binding protein administration of adriamycin(p=0.006, p=0.001 and p= 0.26, p=0.001, respectively). inactivation such as FAK; this effect could be enhanced by co-incubation with IGF-I. We At the 16th week, UPr/Cr ratio was similar between groups of DT and TT(p=0.1),while in had previously shown that exogenous Hic-5 induces proteinuria in normal rats, and QT group it was significantly lower than that of TT group(p=0.001). Serum creatinine enhanced Hic-5 expres-sion in podocytes precedes the onset of proteinuria in puromycin- levels in QT group was significantly lower than the groups of DT and TT(p=0.002, induced nephrosis. Conclusion: These in vivo and in vitro data demonstrate that IGFBP-2 is p=0.015, respectively). Serum albumine and triglyceride levels, interstitial fibrosis and an important aggravating factor in the pathogenesis of FSGS by induction of Hic-5 TGF-beta scoring of the histological examination of kidney were not significantly different expression in podocytes. between the groups of DT, TT and QT. We showed the better effect on decreasing proteinuria and preserving renal function with combination of ACEI, AT1RB and statin plus high-dose immunoglobuline in experimental nephrotic syndrome. Quadruple therapy might be suggested as a new alternative treatment protocol in children with SRNS. Pediatr Nephrol (2006) 21:1493–1635 1509

COD. OP 9 COD. OP 10 The expression of heat shock protein 47 in experimental pyelonephritis APOPTOSIS IN CHILDREN WITH CHRONIC RENAL FAILURE N Biyikli, H Tugtepe, F Cakalagaoglu, H Alpay, A Ilki N Biyikli (Marmara University (CRF) Medical Faculty, Department of Pediatric Nephrology) H Tugtepe (Marmara University I Makulska, D Zwoliñska, A Chybicka, D Noworolska Medical Faculty, Department of Pediatric Surgery) F Cakalagaoglu (Marmara University Department of the Pediatric Nephrology, Wroc ùaw Medical University , Curie-Sklodowska Medical Faculty, Department of Pathology) H Alpay (Marmara University Medical Faculty, 50/52 , 50-369 Wrocùaw , Poland Department of Pediatric Nephrology) A Ilki (Marmara University Medical Faculty, Department of Microbiology) Apoptosis is a programmed active and selective mechanisms of cell death allowing for the , Kozyatagi Sinan Ercan Cad, Oztor Sitesi, C blok 38/38 , 34736 Istanbul , Turkey removal of cells in the living organisms. The aim: was to estimate activity of apoptosis in peripheral blood mononuclear cells of children and young adults with chronic renal failure. Heat shock protein (HSP) 47 has been identified as collagen binding stress protein, shown Objective: 51 patients with CRF (36 male, 34 female, mean age 10,5 year) were enrolled to have a specific role in the intracellular processing of procollagen molecules during into the study. Patients were divided into 3 groups. Group I- 24 predialysed patients, group collagen assembly. Recent studies focus on the expression of HSP 47 in experimental II- 13 hemodialysed (HD) patients, group III- 14 patients on peritoneal dialysis (PD). models of sclerosis/fibrosis. In this study we aimed to assess the expression of HSP 47 in Control group consisted of 19 healthy age-mached subjects. Methods: To identify early and experimental acute and chronic pyelonephritis. 13 Wistar rats were injected 0.1 ml solution late phase of cells undergoing apoptosis Annexin V-FITC and propidium iodide (PI) were containing E.coli ATCC 25922 1010 cfu/ml into left renal medullae. 10 rats were designed used and measured by means of flow cytometry. Fas Ligand and Bcl-2 proteins activity as sham group and were given 0.9 % NaCl. Pyelonephritic rats were sacrificed at 24th hour were investigated also. Results: In predialysed children cell apoptosis (both phases) was (acute pyelonephritis group, PN1, n: 6) and 1st week (chronic pyelonephritic group, PN2, n: higher compared to the controls and both groups of dialysed patients, but the difference was 7) after E.coli injection. Half of the sham group rats were killed in the 24th hour (S1) and not significant. The activity of Fas Ligand protein was similar in every group. The Bcl-2 the rest were killed after 7 days (S2). Renal tissues were studied histopathologically by protein activity was higher in HD i PD patients and we found significant differences Hematoxylin and Eosine and scored for the diagnosis of pyelonephritis. The HSP 47 between HD and predialysed and control group (p=0,002). Positive correlations between expression was studied semiquantatively by immunohistochemical staining by HSP 47 Fas Ligand and Bcl-2 in HD (p=0,01) and predialysed children (p=0,008) were identified. [HSP 47 (H-300) Santa Cruz Biotechnology]. Acute (PN1) and chronic (PN2) Negative correlations between late phase of apoptosis and Bcl-2 in HD and control group pyelonephritic histopathological changes were shown in experimental pyelonephritic were found. Conclusions. The highest rate of apoptosis in predialysis children suggest that groups. HSP 47 expression showed a statistically significant increase in both of the uremic toxins play a significant role in this phenomenon. The significantly enhanced pyelonephritic groups (PN1: 2.3 ± 0.5, PN2: 3.1 ± 0.7) in respect to sham groups (S1: 1± 0, activity of Bcl-2 protein in dialysed patients probably protected from apoptosis. S2: 1.2 ± 0.4) (S1 versus PN1: p: 0.000, S2 versus PN2: p: 0.000). Stronger immunostaining for HSP 47 was noted in the chronic pyelonephritic group than the acute pyelonephritic group (p: 0.038). We conclude that increase in renal HSP 47 expression shown in experimental acute and chronic pyelonephritis is one of the responsible factors for the fibrotic changes of persistent renal damage.

COD. OP 11 COD. OP 12 TREATMENT OF PRIMARY NOCTURNAL ENURESIS WITH Autoimmune haemolytic and uraemic syndrome (HUS) due to auto FUNCTIONAL MAGNETIC STIMULATION anti-factor H (FH) antibodies N M Varda, Maribor Teaching Hospital, Department of Paediatrics I But, Maribor Teaching B Ranchin1, MA Dragon-Durey2, JL André3, S Fargue1, MJ Krier3, C Veysseyre4, A Hospital, Department of Gyneacology Liutkus1, V Frémeaux-Bacchi 2, P Cochat1 1. Département de Pédiatrie, Hôpital Edouard- Maribor Teaching Hospital, Department of Pediatrics , Ljubljanska ul. 5 , 2000 Maribor , Herriot, Lyon, 2. Service d`Immunologie Biologique, Hôpital Européen Georges- Slovenia Pompidou, Paris, 3. Département de Pédiatrie, Hôpital Brabois, Nancy, 4. Service d`Immunologie, Centre Hospitalier Lyon-Sud, Lyon - France Objectives: The aim of our pilot study was to evaluate the potential clinical and urodynamic Département de Pédiatrie, Pavillon S , Hôpital Edouard Herriot , 69437 Lyon , France effects of functional magnetic stimulation (FMS) compared to a placebo in the treatment of girls with primary nocturnal enuresis (PNE). Three cases of HUS due to the development of auto-anti-FH antibodies leading to acquired Methods: Twenty girls with PNE (mean age 10.8 years, range 6-14 years) were included in FH deficiency have been currently reported. We report on a boy who presented with post- the study and randomly divided into two groups, the active FMS group (10 girls) and the diarrhoea HUS, low plasma C3 and FH antigen with circulating auto-anti FH antibodies. placebo group (10 girls). All girls were asked to wear the PULSEGEN stimulators in a Bacteriological investigation showed no sign of E coli infection nor verotoxin. Plasma FH small pocket of the specially designed underwear day and night for two months. FMS was antigen was normal in both parents. Plasma factor B and I antigens were normal in the applied continuously at 18.5Hz. Clinical parameters were documented and urodynamic patient; sequencing of factor H, I, and CD46 genes showed no abnormality. No other evaluation was performed before and after FMS. Data were analyzed using non-parametric circulating auto-antibody was detected. The management of the patient first included statistics. haemodialysis (from D0) and fresh frozen plasma infusion (D37-D50), followed by 7 Results: The number of weekly PNE episodes decreased significantly after FMS compared plasma exchanges (PE) after evidence of auto-IgG (D53-D67). Plasma C3 and FH levels to the placebo (p=0.007). In the active group the number of PNE episodes fell from 3.1 to further normalized and antibodies titre decreased without any improvement of GFR. 1.3 per week (p=0.028). Three girls from the active group were completely dry and 4 were Another episode of decreased C3, FH and haptoglobine levels with increase of FH auto significantly improved. In the FMS group a significant (p=0.022) increase in bladder antibodies was noted 2 months after PE discontinuation, while renal biopsy (D129) showed volume at the strong desire to void was observed (from 215.3 to 264.3 ml). Also, an active thrombotic microangiopathy. PE were restarted together with prednisone and increase in bladder volume at the first desire to void was observed (from 106.3 to 140.5 ml), azathioprine (D135). Antibodies titre decreased followed by C3, FH and haptoglobine although this was not statistically significant (p=0.059). levels normalisation on D172, so that PE could be discontinued after 2.5 months (14 PE Conclusion: According to preliminary results of our study, we feel that FMS represents a sessions). Four months later, plasma C3, FH and haptoglobine remained normal, and GFR new effective method for the treatment of girls with PNE, at least for some subtypes of this slightly improved leading to less dialysis requirements. This case report strongly suggests to disorder. assess anti-FH antibodies at the early phase of HUS associated with low plasma C3 in order to allow specific management (PE and immunosuppression) to be started promptly. 1510 Pediatr Nephrol (2006) 21:1493–1635

COD. OP 13 COD. OP 14 FOUR GENERATIONS OF A FAMILY WITH VON HIPPEL- Cyclosporine A treatment in pediatri c patients with X-linked Alport LINDAU SYNDROME Syndrome: a single centre experience. F Mutlubas presenting author S Mir A Dinle r A Legato, F Emma, L Massella Bambino Gesù Children’s Hospital and Research Institute, Ege University Faculty of Medicine Pediatric Nephrology Department , Ege University Rome, Italy. Faculty of Medicine Pediatri Bornova , 35100 Izmir , Agean Turkey Bambino Gesù Children’s Hospital and Research Institute , Nephrology and Urology, P.zz a S.Onofrio, 4 , 00165 Rome , Italy Phaeochromocytoma is rare in children, but when found it is often extra-adrenal, multifocal, and associated with hereditary syndromes. Syndromes occur in multiple endocrine Cyclosporin A (CsA) as been proposed to decrease proteinuria and progression of chronic neoplasia type2, Von Hippel-Lindau syndrome(VHL),neurofibromatosis type1, and familial renal faiulure (CRF) in patients with X-linked Alport Syndrome (X-AS) (Callis et al Kidney paragangliomas. Phaeochromocytoma was defined in four generations of this family with a Int. 1999). complaint of headache of a 6 years old boy from the third generation as VHL type2 The efficacy of CsA was evaluated prospectively in a group of 13 males and 1 female syndrome. pediatric patients with X-AS (mean age 16 yrs, range 8-28 yrs). At the initiation of CsA therapy, 5/14 patients had CRF (creatinine clearance = 5412 CASE 1 ml/min/1.73mq) and 9/14 patients had normal renal function (creatinine clearance = 110 17ml/min/1.73mq). CsA was initiated at dose of 5 mg/kg/d and adjusted to maintaining C2 Sustained hypertension (Blood pressure:160/110 mmhg) was detected in 6 years old boy plasma levels in a range of 400-500 ng/ml. with headache. Doppler USG demostrated a hypoecoic solid lesion in 1.7cm lenght at Results: 3/14 patients progressed to end-stage renal failure (ESRF) within 12 months. The retrocaval. This lesion was surrounding the renal artery. Both neuroblastoma and remaining 11 patients had a baseline protU/creatU ratio of 2.81.7 mg/mg and have been paraganglioma were thought in diagnosis at first. Catecholamines and metabolites were followed for 42 months. After 1 month of treatment, the protU/creatU ratio decreased to 1,0 high. Abdominal MRI suggested a retrocaval lesion whereas I-131MIBG showed bilaterally 1.1 mg/mg (median time to reach a 50% decrease in proteinuria from baseline: 2.8 affected adrenal glands with paravertebral area. The lesion had seen originated from weeks), but increased progressively thereafter to reach 1,71,7 mg/mg at 42 months o f paraaortic sympathic ganglia in neighbourhood with right adrenal gland in operation and follow-up. By Kaplan-Meier estimation, half of the patients had a 25% decrease in paraganglioma histology. creatinine clearance after 7.5 months of treatment. At 42 months of follow-up, 3/11 patients Many cases with malign tumors, (liver lesions,uteruscarsinomas, intracranial tumors), showed a decline of their creatinine clearance > 50% from baseline. isolated or combined blidness and a patient who had adrenelectomy in another center had Conclusions: CsA treatment in X-AS patients with CRF has no benefits and may accelerate learned from family history(Figure 1-2). progression to ESRD. In patients with normal renal function CsA allows to decrease Eleven years old brother of this case was checked up without any complaint. He had also significantly proteinuria, but has questionable benefits in controlling the progression of gone on adrenalectomy. CRF. Although cases without family histories and with paraganliomas could thought to be familial paraganglioma syndrome, VHL Type2 is the most appropiate diagnose with individuals from different generations with many tumoral lesions and blidness. To investigate germ line mutations for VHL and SDHB-SD-HD genes can be the best diagnostic manegement for suspected members of this family.

COD. OP 15 COD. OP 16 LONG TERM IMPLICATIONS OF INFLAMMATION IN IgACE: FIRST MULTICENTRIC PROSPECTIVE DOUBLE BLIND FAMILIAL MEDITERRANEAN FEVER ASSESSED BY INTIMA RANDOMIZED AND PLACEBO CONTROLLED STUDY ON ACE- MEDIA THICKNESS: A PREDICTOR FOR ATHEROSCLEROSIS ? INHIBITORS (ACE-I) ADMINISTRATION IN MODERATELY Bilginer Y*, Basaran C, Ozaltin F, Duzova A, Besbas N, Topaloglu R, Ozen S, Ozmen M, PROTEINURIC IgA NEPHROPATHY (IgAN) IN THE YOUNG. Bakkaloglu A. * Presenting Author *R. Coppo, *L. Peruzzi, *A. Amore, *D.Mancuso, *A. Piccoli, °P.Cochat, °R.Stone, ° Hacettepe University School of Medicine , Pediatric Nephrology and Rheumatology Unit , M.Kirschstein, °T.Linné *Nephrology, Dialysis and Transplant Unit, Regina Margherita 06100 Ankara , Turkey Children Hospital, Turin, Italy °on behalf the EC Biomed Concerted Action Project BMH4- 97-2487(DG 12-SSMI) and IgACE European Collaborative Group. Background:Familial Meditereanean Fever (FMF) is an autosomal recessive disorder Nephrology, Dialysis and Transplant Unit, Regina Margherita Children Hospital , Piazza characterized by recurrent episodes of fever and serosal inflammation. Although FMF is a Polonia, 94 , 10126 Turin , Italy periodic diseaese recent data have suggested that a continuous subclinical inflammation is present. This European Community Biomedicine and Health Research supported, multicentric, Aim: To determine whether arterial wall thickening is advanced in FMF patients compared randomized, placebo-controlled, double-blind trial, prospectively investigated the effect of with healthy controls by measuring the intima-media thickness (IMT) of the common ACE-I in children and young IgA Nephropathy (IgAN) patients (<35 years old) with carotid and internal carotid arteries and to evaluate the role of clinical and laboratory moderate proteinuria (>1g<3.5 g/day/1.73m2) and creatinine clearance (CrCl) features on IMT of carotid arteries. >50ml/min/1.73m2. Fifty-seven patients, 19.9(9 –35) years old, randomized to receive Methods: IMT and levels of serum hemoglobin, sedimentation, C-reactive period(CRP), Benazepril 0.2 mg/Kg/day (ACE-I) or placebo (PL) completed the trial (median follow-up serum amyloid A protein (A-SAA), lipid profile and homocysteine were examined in 70 42 months). The primary outcome was progression of kidney disease, defined as >30% FMF patients who have positive MEFV mutations in attack free period(median age 14 (4- decrease of baseline CrCl and/or worsening of proteinuria untilQ 3.5g/day/1.73 m2. 24)), and 26 age, sex and body mass index matched healthy controls (median age 14 (4- 18)). The common carotid arteries (CCA) were evaluated in patients and control subjects, Secondary outcome was proteinuria partial (<0.5g/day/1.73m2) or total remission with a high resolution B- mode ultrasonography in multipl projections to optimize detection (<160mg/day/1.73m2) for >6 months. The survival to the events was evaluated by of carotid IMT. univariate (Kaplan-Meier, log-rank test) and Cox multivariate analysis. Results: IMT of CCA were significantly higher in FMF patients than in healthy controls The annual change in CrCl accounted for –2.18 ml/min/year/1.73 in PL versus +4.97 (0.37 (0.26-0.61) versus 0.28(0.21-0.35) p<0.001). There was a positive correlation between ml/min/year/1.73 in ACE-I, P=0.014. A single patient (4.3%) in the ACE-I group and 5 A-SAA and CCA intima-media thickness (r =0.431; p<0.001). There was no correlation (14.7%) in the PL group showed a worsening of CrCl >30%. No patient on ACE-I between IMT and other clinical and laboratory features. developed nephrotic syndrome, versus 7(20.6%) on PL. The primary outcome of renal Conclusion: We clearly demonstrated that intima media thickness, an early predictor of disease progression resulted significantly different between the two groups (log-rank atherosclerosis, is associated with subclinical inflammation in children with FMF: These P=0.035). A stable partial remission of proteinuria was observed in 13/23(56.5%) ACE-I patients should also be followed up for the development of cardiovascular disease. patients versus 3/34(8.8%) PL (log-rank P=0.033), with total remission in 17.4% of ACE-I treated patients and in none of PL (log-rank P=0.029). The multivariate Cox analysis showed that treatment with ACE-I was the independent predictor of prognosis, while no influence on the progression of renal damage was found for gender, age, baseline CrCl, systolic BP, diastolic BP, MAP, and proteinuria. Pediatr Nephrol (2006) 21:1493–1635 1511

COD. OP 17 COD. OP 18 EFFICACY OF MYCOPHENOLATE MOFETIL (MMF) IN Randomised controlled trial of oral versus sequential intravenous/oral STEROID DEPENDENT NEPHROTIC SYNDROME (SDNS), A cephalosporins in DMSA scintigraphy-documented acute pyelonephritis PROSPECTIVE STUDY K Buechner, E Girardin*, C Berger, U Willi, D Nadal, TJ Neuhaus for the Swiss 1V Baudouin, 2A Bensman, 3JL André, 4F Bouissou, 5F Broux, 6V Guigonis, 7P Niaudet, Pyelonephritis Study Group Presenting author: K Buechner 8M Tsimaratos, 1AL Lapeyraque, 1C Loirat 1Hôpital Robert Debré, Paris, France; 2Hôpital University Children`s Hospital , Steinwiesstrasse 75 , CH-8032 Zurich , Switzerland Trousseau, Paris; 3Hôpital d’enfants, Vandoeuvre-les Nancy, 4Hôpital des Enfants, Toulouse, 5Hôpital charles Nicolle, Rouen, 6Hôpital Dupuytren, Limoges ; 7Hôpital des Aim of the study: Comparison of oral versus sequential intravenous/oral antibiotics in Enfants Malades, Paris, 8Hôpital de la Timone, Marseille. children with DMSA-documented pyelonephritis. Hôpital Robert Debré-APHP , Service de Néphrologie, 48 bvd Sérurier , 75019 Paris , Methods: 235 children aged 6 months to 16 years with a febrile urinary tract infection – France rectal temperature 38°, elevated CRP > 10 mg/l, bacterial growth in cultures from urine collected by catheter – were prospectively randomly assigned to receive either oral Objective : to assess the efficacy of MMF in SDNS ceftibuten (9 mg/kg once daily) for 14 days or intravenous ceftriaxone (50 mg/kg once Materials et methods: patients with SDNS treated with alternate day prednisone and who daily) for 3 days, followed by oral ceftibuten for 11 days. 1st DMSA scintigraphy to detect had already received cyclophosphamide were included at the time of relapse if prednisone acute renal lesions was performed within 5 days. Micturition cystogram and 2nd DMSA threshold > 15 mg/m²/48h and 2 or more relapses per year, and/or body weight > 2 SD were performed after 6 weeks and 6 months, respectively. Exclusion criteria were normal above normal for height and/or height increase < 1 SD in the previous year. 1st scintigraphy, complex renal malformations and septical appearance. Treatment consisted in MMF 1200 mg/m²/d in 2 divided doses and prednisone decrease to Results: 150 children (64%; 132 females (f), 18 males (m); median age 25 months, range 6 50% of threshold dose at month 3, 25% at month 6. Failure of MMF was defined by the – 189) had acute lesions on DMSA. 79 (53%; 71 f, 8 m; median age 27 months) were given occurrence of a relapse in the first 6 months. ceftibuten, 71 (47%; 61 f, 10 m; median age 20 months) ceftriaxone/ceftibuten. One patient Results: 21 patients (18 boys, median age at inclusion 5y10m (3y-14y5m)) were included. from the oral regimen was switched to intravenous therapy due to repeated vomiting. The Mean number of relapses during the year before inclusion was 3 (1-5), and mean threshold 2nd DMSA showed persistent lesions (scars) in 19 children (24%; 18 f, 1 m) with ceftibuten dose of prednisone was 32±15mg/m²/48h. One patient was secondarily excluded because of versus 33 (46%; 29 f, 4 m) with ceftriaxone/ceftibuten (p = 0.004). Vesicoureteric reflux non-compliance. At 3 months (n=20), 1 patient had relapsed and mean dose of prednisone was present in 25 (48%) of 52 children with scars and in 39 (40%) of 98 children without of non-relapsing patients was 17.5±7mg/m²/48h, At 6 months (n=20) , 2 other patients had scars (p = n.s.). relapsed and mean dose of prednisone was 10±2mg/m²/48h. At 1 year (n= 15), 2 additional Conclusions: In children with DMSA-documented pyelonephritis, once daily oral ceftibuten patient had relapsed and mean dose of prednisone was 7.7±3mg/m²/48h. Side effects of for 14 days is effective, safe and convenient. MMF occurred in 3 patients: 1 had anemia which resolved with decreasing MMF to 900 mg/m²/d, 1 transient abdominal pain and 1 transient anorexia. Statistical analysis of clinical outcome with MMF pharmacokinetics is in progress. Conclusion: MMF is effective in reducing prednisone dose in SDNS without major side effects. It can now be proposed instead of cyclosporine when prednisone dose to maintain remission leads to side effects

COD. OP 19 COD. OP 20 Concordance between the indirect radionuclide cystography and the The insignificance of low-grade vesicoureteral reflux voiding cystourethrography Swerkersson S, Andreasson AC, Jodal U, Sixt R, Stokland E, Hansson S. F Cachat, P Balice, E Girardin, A Boubake r , De la Gardievägen 35 , S-53152 Lidköping , Sweden Pediatric Department, Pediatric Nephrology Unit , Rue du Bugnon , 1011 Lausanne , Vau d Switzerland Purpose While the trend today is that vesicoureteral reflux (VUR) is clinically insignificant, still Aim of the study children with low-grade VUR in many centers are being treated either with prophylactic To study the concordance between indirect radionuclide cystography (IRC) and antibiotics or by active measures such as endoscopic procedures. In this study of a conventional voiding cystourethrography (VCUG) populationbased cohort of children, detected after their first symptomatic urinary tract infection (UTI), special focus was put on the role of low-grade (grade I-II) VUR in terms of Methods risk of recurrent infections and permanent renal damage. We compared the results of IRC performed after I123-hippuran renography and VCUG in Methods 91 children (182 renal units) aged 0-9 years, with respect to the presence or absence of We performed a retrospective analysis of infection pattern and renal status (DMSA vesicoureteric reflux (VUR). Concordance of the results was using Fisher’s exact test scintigraphy) according to grade of VUR in patients admitted to the Children’s Hospital. Antibacterial prophylaxis was given only to patients with high-grade VUR (grade III-V). Results Results We found a poor concordance for the presence or absence of VUR between IRC and During a 3-year period 336 children <2 years were available for analysis. VUR was found VCUG. VUR was seen or excluded on both exam (concordance) in 115 units (63%). If we in 55 children (grade I-II in 33, grade III-V in 22) and permanent renal damage in 69 (20%). consider VCUG as the gold standard, IRC diagnosed VUR whereas VCUG did not in 59 During a median follow-up of 2 years, recurrent febrile UTI occurred in 14%, 15% and 50% units (24 patients) (false positive rate 38%). IRC did not detect VUR in 8 units whereas in children with no reflux, VUR grade I-II and grade III-V, respectively. Corresponding VCUG did (9 patients) (false negative rate 29%). The negative predictive value of IRC was figures for permanent renal damage were 16%, 18% and 86%. 70%. Overall, IRC was more sensitive (92%) but less specific (24%) than VCUG. If we Conclusions considered IRC as the gold standard, sensitivity and specificity of VCUG was 61% and There was no increased risk of recurrent infections or permanent renal damage in children 70%, respectively. Expected agreement between both exams was only 23% (kappa 0.0319) with low-grade VUR compared to children without VUR. In contrast, this risk was when we compared the grading of VUR on both exams (mild, moderate and severe IRC significantly increased in children with high-grade VUR. Long-term prophylaxis or grading corresponding to grade I-II, III and IV-V, respectively surgical/endoscopic intervention for children with low-grade VUR is unnecessary.

Conclusions We found a poor agreement between IRC and VCUG for the detection of VUR. IRC was more sensitive than VCUG but its clinical significance and impact on patient management remains to be defined 1512 Pediatr Nephrol (2006) 21:1493–1635

COD. OP 21 COD. OP 22 Proteomic Analysis of Urine in Kidney Transplant Patients with BKV Nephrotoxicity using cyclosporine A (CSA) based immunosuppressive Nephropathy regimens in rat trachea transplantation T Jahnukainen, D Malehorn, G Gupta, M Sun, J Lyons-Weiler, W Bigbee, P Randhawa, R AJ Szabo1, D Yang2, A Vanny3, A Nagy2, RM Langer4, G Losonczy2, G Reusz1, V Pelikan, M Hauskrech and A Vats Müller2 I. Department of Pediatrics1, Pulmonology2, Szentágothai Knowledge Center3 and , Children`s Hospital of Pittsburgh, Department of Pediatrics, 3705 Fifth Avenue , PA Department of Transplantation and Surgery4, Semmelweis University, Hungary 15213 Pittsburgh , Pennsylvania USA I. Dept. of Pediatrics, Semmelweis University , Bokay 53 , H-1083 Budapest , Hungary

The differentiation of BK virus nephropathy (BKVAN) from acute allograft rejection (AR) Nephrotoxic side effect of CSA is well known problem following organ transplantation. is an important clinical problem because the treatment is diametrically opposite for the two Bronchiolitis obliterans (BO) is the major cause of graft failure after lung transplantation. conditions. We aimed to develop non-invasive biomarkers to differentiate BKVAN from We investigated the effectiveness of two different immunosuppressive protocols and the AR in adult kidney transplant patients. involvement of growth factors in nephrotoxicity and BO in both genders in a rat model of trachea transplantation. Surface-enhanced laser desorption (SELDI) analysis (Ciphergen) was used to compare Female (F) or male (M) Brown Norway tracheas were heterotopically transplanted into proteomic profiles of urine of 21 BKVAN patients, 28 patients with AR, and 29 patients Lewis recipients of the respective gender and treated for 21 days with either high dose CSA, with stable graft function (control). Urine samples were analyzed using two different chips reduced dose CSA plus Sirolimus (CSA-SRL) or vehicle. Histology, as well as (IMAC30 and CM10). The data was analyzed using the Ciphergen Biomarker Patterns transforming growth factor (TGF)â (profibrogenic) and bone morphogenic protein (BMP-7) software and bioinformatic software programs developed by us. (anti-fibrogenic) mRNA expression in the grafts and kidney was analyzed, and nephrotoxicity assessed. The patient demographics (age, gender, race, or donor type) did not differ significantly CSA and CSA-SRL treatment decreased histological signs of BO and associated with between the study groups. SELDI analysis showed proteomic profiles that were increased TGFâ and BMP-7 mRNA expression in both genders. Vehicle treatment induced significantly different in BKVAN vs. AR and control groups. Bioinformatic analysis severe BO and significantly decreased expression of TGFâ and BMP-7 without gender allowed distinction of BKVAN from AR with a sensitivity of 64 % and a specificity of 74 differences. CSA-SRL treatment resulted in increased proteinuria and blood urea nitrogen % and BKVAN from controls with a sensitivity of 82 % and a specificity of 88 %, levels. In kidney cortex in M CSA-SRL treatment increased TGFâ expression, while no respectively. A peak at 11.3 kDa was one of the most significant peaks differentiating differences were seen in M kidney medulla and in F both in cortex and medulla. In contrary, between BKVAN vs. AR (P=0.0003). in M in cortex BMP7 expression significantly decreased in CSA-SRL group and no significant changes were detected in any other treatment group. Proteomic profiling of urine was able to differentiate BKVAN both from AR and stable In summary, CSA and reduced dose CSA-SRL are effectively suppressing BO by graft function in kidney transplant patients. Non-invasive diagnostic tools for BKVAN increasing the expression of BMP-7 and TGFâ in both genders. Despite reduction of CSA would be especially important in pediatric patients. Future studies based on protein dose, CSA-SRL combination increases the risk of nephrotoxicity. identification of the differentially expressed peaks in SELDI profiles and further Supported by: ETT 184 - 243/2003, OTKA F042563,T042609, OM and Bolyai grants. quantitation by ELISA or similar methods may enhance the clinical utility of our studies.

COD. OP 23 COD. OP 24 Validation of an Abbreviated Pharmacokinetic Profile for the Large UK single centre experience of the use of sirolimus in paediatric Estimation of Mycophenolic Acid Exposure in Pediatric Renal renal transplant patients. Transplant Recipients J Bayreuther M Sinha L Kerkuck J Taylor Evelina Childrens Hospital, Guys and St LT Weber1,2, B Hoecker1, VW Armstrong3, M Oellerich3, B Toenshoff1, and the German Thomas` NHS Trust, Lambeth Palace Road. London SE1 7EH Study Group on MMF therapy and the Tricontinental MMF Suspension Study Group , 42, Frankfurt Road , SE24 9NY London , UK , Pediatric Nephrology, University Children´s Hospital, Lindwurmstr. 4 , 80337 München , Germany Aims: Pharmacokinetic (PK)/pharmacodynamic relationships between the AUC of a 12 h MPA Sirolimus (SRL) has been widely available since 1999. There have been only small dosing interval and the risk of acute rejection have been established in pediatric renal observational studies in children with renal transplants with short follow up. We were transplant recipients. Because full AUC0-12 monitoring is not practical and predose MPA concerned that there were significant undocumented side effects in our patients treated with concentrations correlate only moderately with the corresponding AUC0-12, the estimation SRL and wanted to investigate this further. of MPA exposure by a limited sampling strategy has been suggested. However, before such an algorithm is transferred to clinical practice, it is compulsory to prospectively validate it Methods: in a different data set, in order to avoid biased results. The aim of this investigation was We undertook a retrospective review of the notes of all children commenced on SRL at our therefore to prospectively validate an algorithm based on an abbreviated PK profile in 54 centre. We specifically looked at the change in calculated glomerular filtrate rate (cGFR), pediatric renal transplant recipients (169 PK profiles) on MMF in conjunction with CsA and presence and timing of proteinuria and haematuria. We also reviewed hyperlipidaemia, prednisone on a second data set in a different group of patients with a similar hypertension, infections and haematological effects. immunosuppressive regimen (25 patients, 119 PK profiles). An algorithm based on three PK sampling time points during the first 2 hours after MMF dosing (estimated AUC0-12 = Results: 18.6+4.3xC0+0.54xC0.5+2.15xC2) was able to predict the corresponding MPA-AUC0-12 Fourteen children were commenced on sirolimus. Time from transplant to commencement with a low percentage prediction error (10.7%) and an acceptable correlation of of SRL 2.6years (0 - 10.6). Time on SRL at last follow up 2.4years (0.6 - 3.5). Thirteen determination (r²=0.76). The performance of this algorithm was comparable among children were given SRL as rescue therapy for chronic allograft nephropathy or acute different pediatric age groups. By ROC curve analysis, the calculated MPA-AUC0-12 was rejection and one as induction immunosupression. There was no improvement in cGFR able to differentiate between rejecters and non-rejecters with a comparable prognostic after commencement of SRL, change in blood pressure or antihypertensive use. Four sensitivity (66.7%) and specificity (61.9%) as the full-time MPA-AUC0-12. In conclusion, children developed heavy proteinuria and haematuria associated with declining renal the use of this validated algorithm for the estimation of MPA exposure has the potential to function. Four others developed both haematuria and proteinuria, two more developed optimize MMF therapy in pediatric renal transplant recipients. either haematuria or proteinuria alone. Eight children required a statin. There was a small but significant decline in haemoglobin and platelets. Two children had significant septic episodes. SRL therapy was withdrawn in three children.

Conclusion: In our experience SRL did not lead to any improvement in GFR when commenced for rescue therapy. It is associated with potentially serious complications; this should be considered when its use is being contemplated. Pediatr Nephrol (2006) 21:1493–1635 1513

COD. OP 25 COD. OP 26 A multicenter, placebo-controlled trial evaluating the efficacy and PROTEIN A IMMUNOADSORPTION IN CHILDREN WITH POST- safety of Basiliximab (Simulect ) in combination with CsA, MMF and TRANSPLANT FSGS RECURRENCE steroids in pediatric renal allograft recipients: 12 months results E Simkova, K Vondrak, J Vavrinec, J Dušek, J Kreisinger,P Dvorak, T Seeman, F Fencl,J B Tönshoff1 G Offner2, B Hoecker1, L Pape2, W Rascher, T Neuhaus, B Hoppe, U Janda Querfeld, M Bulla, G Klaus, K Latta, H Leichter, H Fehrenbach, S Wygoda, J Misselwitz, Paediatric Dpt.University Hospital Motol Prague , Paediatric Dpt.University Hospital, V C Montoya, D Mueller-Wiefel, M Foulard, P Hoyer, P Cochat, W Fischer3, and LB Uvalu 84, Prague 5 - Motol Prague , 15000 Prague , Czech Republic Zimmerhackl4, for the Simulect® DE01 study group. 1University Children’s Hospital, Heidelberg, 2Children’s Hospital, Medical School, Hannover, Germany; 3Novartis Pharma, Focal segmental glomerulosclerosis (FSGS) is a common cause of renal insufficiency and Germany and 4University Children’s Hospital, Innsbruck, Austria has a high tendency to recur after renal transplantation (TX), (reported between 20 and University Chiildren`s Hospital , Im Neuenheimer Feld 150 , D-69120 Heidelberg , 40%, single centre up to 60%) and often leads to renal allograft loss. Different therapeutic Germany approaches have been used. We present two children successfully treated by protein A immunoadsorption (IA). This is the first pediatric, placebo-controlled study to investigate whether basiliximab, a Patient 1 - Now 15-year-old girl with a recurrence of FSGS immediately after TX in April chimeric monoclonal IL-2 receptor antibody in combination with MMF (CellCept , 1200 05, proteinuria (PU) max. 19 g/day. Partial remission of PU 2 g/day was achieved by mg/m² per day), CsA (Neoral ) and steroids could reduce the incidence of acute rejections intensifying immunosuppressive and plasmapheresis (PF). 3 months after TX daily PF was without increasing adverse events. Methods: 202 patients, aged 1-18 years were randomized performed again due to PU 8g/day. In November 05 new relaps was successfully treated by in this prospective, double-blind, multi-center study to receive either basiliximab or placebo 11 daily IA. PU dropped again to 2g/day. Recently she has been treated by weekly IA. on day 0 and 4. CsA was adjusted to target trough levels of 150-250 ng/ml for the first 3 Altogether 33 IA has been performed and PU is 4g/day. months and 100-200 ng/ml thereafter. A protocol biopsy was performed at month 6. Patient 2 - Now 15-year-old girl with a recurrence of FSGS immediately after TX in Results: 193 patients (ITT) received at least one dose of study medication (basiliximab January 04. Remission was achieved by intensifying immunosuppressive and PF. n=100, placebo n=93). Age was 10.7 4.6 and 10.8 4.9 years and HLA mismatch 2.6 1.2 and Proteinuria was stable on consecutive monthly PF and since May 05 on monthly IA. In 2.2 1.0 for basiliximab vs. placebo. The incidence of biopsy proven acute rejection (BPAR) February 06 proteinuria appeared again (1.5g/day) and relaps of FSGS was treated by daily Banff grade I-III at month 6 was 11.0% on basiliximab compared to 16.1% on placebo IA. Remission was achieved after 5 IA (PU 150 mg/day). Recently the girl has been on (n.s.). Five patients in each group had presumptive rejection. Antibody therapy for steroid- monthly IA and PU remains low. resistant rejection was given in 3 patients on basiliximab and 5 patients on placebo. Two Protein A immunoadsorption (IA) proved effective in reducing proteinuria in patients with graft losses, one in each group, were observed. Two deaths occurred in the basiliximab recurrence of FSGS. Controlled and randomized clinical trials are needed. group during the first 6 months. The overall incidence of adverse events was similar in both Supported by grant VZ FNM 00064203/6906 groups. 2 patients on basiliximab and 5 patients on placebo developed PTLD. Conclusion: The incidence of BPAR was numerically, but not significantly lower on basiliximab. I f basiliximab has an effect on long-term results, is subject to future evaluations.

COD. OP 27 COD. OP 28 PEDIATRIC RENAL TRANSPLANT. SHORT AND LONG-TERM Factors influencing growth after transplantation EVOLUTION S Cohen*, G Guest*, M Charbit*, P Taupin**, MF Gagnadoux*, O Gillion*, P Niaudet* C García Meseguer, A Alonso, M Melgosa, A Peña, L Espinosa, C Fernandez Camblor, J Hôpital Necker-Enfants-Malades, Service de néphrologie pédiatrique*, Service de Bravo, M Navarro Presenting Author: C Garcia Meeseguer biostatistique médicale**, 149 rue de Sèvres, 75015 Paris, France Children Hospital "La Paz".Pediatric Nephrologyi , Pº Castellana nº261 , 28046 Madrid , Service de néphrologie pédiatrique , 149, rue de Sèvres , 75015 Paris , France Spain Growth data were evaluated in 148 children who received first kidney transplantation in our AIM : To describe characteristics of renal transplant (Tx) in children, and their evolution, department from january 1995 to december 2003. Immunosuppressive therapy consisted of based in 21 years of experience. induction, then prednisone associated with anticalcineurin therapy (ciclosporine for all PATIENTS AND METHODS: From I-1985 to XII-2005 we performed 274 Tx in 229 patients but one with FK506) and azathioprine (n=139) or mycophenolate mofetil (n=9). children (148 boys, 81 girls). They received first Tx: 225 and 49 retrasplants. Cadaver Prednisone dosage was 60 mg/m2 at day 1, 15 mg/m2 at day 60, 7,5 mg/m2 at 6 months, donor in 225 and living donor in 49 (18 father, 31 mother), 5 received a hepatorenal after one year prednisone was tapered to 5 mg/m2/d. Some patients were switched to transplant and one a multiorganic transplant. Primary renal disease was: Uropathy 24,4%, alternate day therapy. No children received growth hormone therapy after transplantation. dysplasia16,5%, glomerulopathy 15,7%, nephronopthisis 11,3%, reflux nephropathy At transplantation, mean age was 10.1 y (1.4-18) and mean standard deviation score for 11,3%,others 14%.The initial treatment was:Tx 22%, peritoneal dialysis 50% and height was -1.87 (-6.79 to +3.2). Fifteen patients had reached adult height. Mean final haemodialysis 28%. Mean receptor age at 1rs Tx 10,5 ±5,11 years (15 under two years). height was 156cm (-0.9 SDS) for girls and 171cm (+0.7 SDS) for boys. Mean donor age 14,2±14,4 ( 49,7% under 6 years). Initial graft function was obtained in After transplantation, children did not manifest catch-up growth and median Z score 94,5% . remained suboptimal, pubertal growth gain was minimal: mean height SDS was -1.74 at yr RESULTS: Patient survival is 97,7%, 96,4% and 80,3% at 1,10 and 20 years. The graft 1 (n=148), -1.49 at yr 3 (n=139), -1.79 at yr 5 (n=109), -1.77 at yr 8 (n=60). Major survival is 87,7%, 72,6% , 53,9% and 24,7% at 1,5,10, 20 years. Graft survival is superior predictive factors of optimal growth were glomerular filtration rate in the current period: 81,4% at 1rs year in period 1985-90 vs. 92,2% in 1997-2002 and (p< 0.009) and absence of acute rejection crisis (p<0.0001). No association was found 95,5% in 2003-05. At 5th year 59,2% in 1985-90 vs. 79,6 in 1997-02 (p=0,083), in living between optimal growth and corticosteroid dosage (mg/m2/day) or mode of administration related donor versus cadaver donor 97,9% , 88,6%, 76,7% at 1,5, 10 years vs. 88,7%, 76,7% (daily/alternate day therapy). Mean final height acquired during transplantation was 153.3 y 47,1% respectively (p=0,065), in first Tx in comparison with retrasplant: 89,9%, 75,6% cm (-1.6 SDS) for girls (n=11) and 166 cm (-1.5 SDS) for boys (n=13). and 56,2% at 1,5,10 years versus 77,1%, 58,5% y 43,2% respectively (p= 0,047). Conclusion : growth after transplantation remains suboptimal, stressing the importance of Donor age, receptor age, ischemia time and previous dialysis didn’t affect survival of 1rs growth management during the course of chronic renal failure. After transplantation, the graft of cadaver donor. We found statistical significance with initial graft function (p= most important positive predictors were good allograft function and absence of acute 0,0001)and minimal creatinine achieved (p= 0,01). rejection crisis. SUMMARY Results of paediatric renal transplant continues to improve. The percentage of retransplant in children is high and their prognostic is worse. The transplant of living related donor is an excellent option for children. 1514 Pediatr Nephrol (2006) 21:1493–1635

COD. OP 29 COD. OP 30 Combined liver kidney transplantation in children: multi-centre report Predicting the Clinical Outcome of Congenital Unilateral Ureteropelvic Collard L1, Amore A2, Bensman A3, Bouissou F4, Bourdat G5, deVilledeGoyet J6, Junction Obstruction in Newborn by Urinary Proteome Analysis Gagnadoux MF7, Girardin E8, Janssen F9, Maisin A10, Martini S11, Neuhaus T12, Novo S Decramer 1, 2, S Wittke 3, H Mischak 3, F Bouissou 1, 2, JL Bascands 1 and JP R13, Tsimaratos M14, Van Damme-Lombaerts R15, Vande Walle J16, Cochat P17 Schanstra 1 1, Inserm U388, IFR 31, Institut Louis Bugnard, BP 84225, 31432 Toulouse presenting author : Collard Laure 1 Centre Hospitalier Universitaire, Liège, Belgium 2 Cedex 4, France. 2, Nephropediatric Unit, Hopital des Enfants, TSA 70034, 31059 Ospedale Regina Margherita, Torino, Italy 3 Hôpital Trousseau, Paris, France 4 Hôpital des Toulouse Cedex 9, France. 3, Mosaiques-diagnostics and therapeutics AG, Hannover, Enfants, Toulouse, France 5 Centre Hospitalier Universitaire, Grenoble, France 6 Cliniques Germany. Universitaires St-Luc, Brussels, Belgium 7 Hôpital Necker-Enfants Malades, Paris, France Inserm U388/Pediatric Nephrology , IFR31, BP84225 , 31432 Toulouse Cedex 4 , France 8 Hôpital des Enfants, Geneva, Switzerland 9 Hôpital Universitaire Des Enfants Reine Fabiola , Brussels, Belgium 10 Hôpital Robert Debré, Paris, France 11 Kinderklinik der Congenital unilateral ureteropelvic junction (UPJ) obstruction can lead to chronic Technischen Univ. Munchen, Germany 12 University Children’s Hospital, Zurich, nephropathy in the obstructed kidney. An important issue in UPJ-obstruction is whether Switzerland 13 CHRU Jeanne de Flandre, Lille, France 14 Hôpital des Enfants La Timone, infants should undergo surgery. In the absence of non-arbitrary non-invasive biomarkers to Marseille, France 15 KUL, Leuven, Belgium 16 UZGent, Gent, Belgium 17 Hôpital determine the necessity for pyeloplasty this currently requires repetitive invasive renal Edouard Herriot, Lyon, France diuretic renograms relying on arbitrary threshold values. We used an on-line combination of CHU Sart-Tilman , Néphrologie pédiatrique Domaine universitaire du Sart-Tilman B35 , capillary electrophoresis and mass-spectrometry (CE-MS) to verify if urinary polypeptide B4000 LIEGE , Belgium patterns (UPPs) can be used as non-invasive prognostic biomarkers. Newborn were divided in 4 groups: control (healthy individuals n=13), non-operated UPJ- Since 2001, we collected data from all simultaneous paediatric combined liver kidney obstruction (No_OP, n=28, grade 1/2 hydronephrosis or pelvic dilatation (Pd) 5-15 mm), transplantation (CLKT) performed in France and Belgium; other European centres were possible operation (OP_Poss, n=36, grade 3/4 hydronephrosis and/or Pd>15 mm and mild added since 2005. Such a large database allowed us to analyse outcomes and comparisons functional obstruction (isotopic MAG3 renogram)) and scheduled to be operated (OP, n=39, among different groups according to indication. In the “normal liver” group (group 1), liver grade 3/4 hydronephrosis and Pd>20 mm and functional obstruction). transplantation served as enzyme/gene replacement therapy and renal failure was a “Master” UPPs were obtained for control, No_OP and OP groups. 51 distinct polypeptides consequence of enzyme/gene defect. In the “chronic liver disease” group (group 2), both the allowed to discriminate between the 3 groups. Next, we predicted by EC-MS the clinical liver and the kidney were structurally affected by the same or by two different processes. outcome of the 36 patients in the OP_Poss group using a hierarchic disease model based on From 1987 to 2005, 69 children < 19 years of age underwent CLKT in 16 centres. Group 1 these discriminating polypeptides. 25 patients were predicted to evolve towards the OP included 42 patients (41 primary hyperoxaluria) and group 2 included 27 patients (20 group, 11 towards the No_OP group. Twelve months later the clinical evolution of these congenital hepatic fibrosis). Mean age at CLKT was similar in both groups (8.4±5.3 years). patients was compared with this UPP-based prediction. For 34 out 36 patients the clinical After a mean follow-up period of 6.4±5.6 [0-18.8] years, overall patient, liver graft and evolution correlated with CE-MS prediction. Using CE-MS/MS we identified some renal graft survival rates were 80.6, 74.6 and 68.7%, respectively, without any significant predictive markers. difference between the two groups. These results show for the first time that analysis of urinary polypeptides in newborn with Most of deaths occurred during the first two months post CLKT, mainly due to sepsis and UPJ-obstruction can predict their clinical outcome. bleeding complications. In group 1, there was an increased mortality risk for younger age but not for mean duration on dialysis. Among survivors 85% had a normal renal function with a GFR of 75.7±26.5 mL/min per 1.73 m². The analysis of the largest database on CLKT in children provides encouraging results and may help to define individual transplantation strategies.

COD. OP 31 COD. OP 32 Outcome of critically ill children with continuous renal replacement Acute renal failure in a 3 year-old child as part of a DRESS syndrome therapy following hepatitis A virus infection. E Ring, Rodl S, G Pichler, C Mache, G Zobel A Garnier 1, El Marabet 1, M Peuchmaur 2, O Mourier 3, V Baudouin 1,C Loirat 1 1 Department of Pediatrics , Department of Pediatrics , 8036 Graz , Austria Austria Pediatric Nephrology Unit, Assistance Publique Hôpitaux de Paris, Hôpital Robert Debré, Paris, France 2 Division of Anatomic Pathology, Assistance Publique Hôpitaux de Paris, Continuous renal replacement therapy (CRRT) performed as hemofiltration (HF) or Hôpital Robert Debré, Paris, France 3 Pediatric Hepatology Unit, Assistance Publique hemodiafiltration (HDF) in a arteriovenous or mostly venovenous fashion nowadays is the Hôpitaux de Paris, Hôpital Bicêtre, Le Kremlin Bicêtre, France method of choice for treatment of acute renal failure or removal of toxic metabolites in Hôpital Robert Debré , 48, boulevard serurier , 75019 paris , France critically ill patients. We retrospectively analyzed the data of 115 critically ill children (60 boys, mean age 3.7 We report the case of a 3 year-old melanesian female admitted for acute renal failure years) with CRRT for determinants of outcome (survival / non-survival). Overall mortality following subfulminant hepatitis virus A infection. A non oliguric acute renal failure rate was 43% with a strong variation between diagnoses and age of patients. Neonates and (maximal serum creatinine 295µmol/L) occured after 8 weeks of fever condition and major infants accounted for 46% of non-survivors and 46% of children with cardiac disease died. eosinophilia (30 000/µL), while she was slowly recovering from severe cytolytic hepatitis. 92% of children with isolated primary renal disease survived. In contrast, 53% of children Renal histology displayed diffuse eosinophilic infiltration with severe acute with secondary renal failure died. The number of organ failures and the pediatric risk of tubulointerstitial lesions and moderate endocapillary proliferation with mild glomerular mortality index (PRISM-Score) clearly discriminated between survivors and non-survivors. eosinophilic infiltration. An immunoallergic mechanism for the renal failure was then Sepsis and oncologic disorders had a mortality rate of 45% and 50%, respectively. The considered. The child had received cefixime and trimethoprim-sulfamethoxazole 3 weeks percentage of fluid overload (%FO) clearly distinguished survivors and non –survivors as prior to the first hospitalisation for hepatitis A virus infection. Final diagnosis was DRESS 63% of patients with %FO <20% survived while 75% of children with %FO>20% died. syndrome induced by cefixime. DRESS is the acronym for Drug Reaction with Eosinophilia and Systemic Symptoms, an idiosyncratic delayed drug reaction occuring after first exposure. The hallmark of this syndrome is a major eosinophilia with multivisceral involvement (skin, liver, kidney). Renal involvement is frequently reported in this syndrome but only few histological data is available. DRESS syndrome occurs frequently with concomitant viral infection, especially HHV6 and other Herpes viridae. In our patient, cefixime (first exposure) probably was responsible of the DRESS syndrome rather than trimethoprim-sulfamethoxazole (second exposure). In addition, we postulate that the hepatitis A virus could be involved in the occurrence of the DRESS syndrome and that the severity of the initial hepatitis could be partly explained by the DRESS syndrome. Pediatr Nephrol (2006) 21:1493–1635 1515

COD. OP 33 COD. OP 34 Haemolytic Uraemic Syndrome associated with Invasive Pneumococcal Growth Impairment after Ifosfamide-induced Nephrotoxicity in Disease - The UK Experience Children Presenting Author: L Kerecuk (1) A Waters(2) D Luk(2) MR Haq(2) MM Fitzpatrick(3) L Patzer2, W Stöhr1, M Paulides1, A Kremers1, J Beck1, T Langer1, R Rossi3 (supported RD Gilbert(4) C Inward(5) C Jones(6) CJD Reid(1) M Slack(7) B Pichon(7) W van’t Hoff by APN and GPOH) 1 LESS centre, University Hospital for Children and Adolescents, (2) MJ Dillon (2) CM Taylor(8) K Tullus (2) (1)Evelina Children`s Hospital,Guy`s & Department of Paediatric Oncology, Erlangen, Germany 2 Hospital for Children and St.Thomas` Trust, London (2)Great Ormond Street Hospital, London (3)St James’ Adolescents St. Elisabeth and St. Barbara Hospital, Halle/Saale, Germany 3 Hospital for University Hospital, Leeds (4)Southhampton General Hospital (5)Bristol Royal Hospital for Children and Adolescents, Klinikum Neukölln, Berlin, Germany Sick Children (6)Alder Hey Children’s Hospital, Liverpool (7)Health Protection Agency, Hospital for Children and Adolescents St. Elisabeth and St. Barbara Hospital , Mauerstrasse Colindale, London (8)Birmingham Children`s Hospital. 5 , D-06110 Halle/S. , Germany Guy`s and St. Thomas` NHS Foundation Trust , 45 Gladstone Road, Farnborough , BR6 7DZ Orpington , Kent UK Objectives: To describe long-term consequences of ifosfamide-induced nephrotoxicity on growth in children treated for cancer. There has been an increase in the incidence of haemolytic uraemic syndrome (HUS) Study design: In a retrospective study, departments for paediatric oncology and nephrology associated with invasive pneumococcal disease over the past 3 years in the United in Germany, Austria, and Switzerland were asked to report patients with serious long-term Kingdom. nephrotoxicity after ifosfamide-treatment. Data at first appearance of renal dysfunction and We describe, in the largest series to date, the clinical features, management and outcome in at the last renal examination were collected using a standardized questionnaire. 43 patients identified in 7 UK Tertiary Paediatric Nephrology Centres between 1998 and Results: Fifty-nine patients with tubulopathy (35 severe, 24 moderate) following ifosfamide 2005. 74% of cases occurred in winter months. The median age at presentation was 13 therapy were eligible for analysis of long-term outcome (median follow-up 4 years, range (range 5 – 39) months and male: female ratio was 1.4: 1 (25: 18). Pneumococcal infection 1.1 to 12.9). Median height standard deviation score was significantly reduced at renal was confirmed in 34/43 cases (79%). Pneumonia was a presenting feature in 35 cases (81%) diagnosis, and at last renal examination (–1.7 and –2.1 respectively, p <0.01 at each point in with empyema complicating 23 of the 35 cases (66%). Thirteen patients (30%) had time). Patients with tubulopathy were also stunted in comparison with a control group of confirmed (n=9) or suspected (n=4) pneumococcal meningitis. Thirty-six patients (84 %) cancer patients without renal disease (mean difference at last examination: 7.3 cm (95% required dialysis with median duration of 10 days (range 2 – 240). Six patients received confidence interval: 2.5 to 12.1 cm). In patients with severe tubulopathy, glomerular plasma exchange. filtration rate deteriorated significantly over time. End-stage renal disease was reported in Mortality was 11%: four patients died while on dialysis during the acute illness and one one patient only, not solely caused by ifosfamide. patient remained on peritoneal dialysis and died eight months later. Conclusion: Depending on the extent of tubular dysfunction, patients with ifosfamide- Of those 38 survivors who recovered renal function, estimated GFR data is available for 25 induced nephrotoxicity experienced significant growth impairment and a slow decline in patients with a mean follow up of 9 (range 1 – 63) months. The median GFR was 90 (range glomerular filtration rate. 20 – 180) ml/min/1.73m2, including 5 patients (20 %) with chronic renal failure (GFR <60ml/min/1.73m2). Hypertension was present in 19% (5/27) and proteinuria in 33% (9/27) of patients at last follow up. Cases of D-ve HUS, especially in winter, should alert the clinician of possible pneumococcal infection with T activation.

COD. OP 35 COD. OP 36 UK Cystinosis Registry: 10 year data review “FULL-HOUSE NEPHROPATHY” IN CHILDREN. S Collin W van`t Hoff 1A Gianviti. 1G Stringini. 1E Proietti. 2S Caropreso 3AE Tozzi 4G Barbano 5L Peruzzi 6A , Victoria Ward, Great Ormond Street Hospital, Great Ormond Street , WC1N 3JH London , Frezzolini 7M De Pieri 8A Petaccia 9A Onetti-Muda 1F Emma. 1. Nephrology and Dialysis UK Unit Dept. of Nephrology and Urology. Bambino Gesù Children Research Hospital. Rome 2. Nephrology and Dialysis Unit. Ospedale Santobono. Napoli 3. Epidemiology Unit. Cystinosis is a rare metabolic disorder of cystine accumulation, treated with cysteamine. Bambino Gesù Children Research Hospital. Rome 4. Nephrology, Dialysis and Transplant There are few data on efficacy. The UK Cystinosis Registry was created in 1994 to monito r Unit. Gaslini Institute. Genoa. 5.Nephrology and Dialysis Unit. Osp. Regina Magherita. renal function, growth and treatment. Turin 6. Laboratory of Immunology and Allergology. Ist. Dermopatico dell`Immacolata. In 2004 there were 137 patients (88% known cystinosis patients in UK), in 19 centres. 67% Rome 7. Pediatric Dept. University of Padua. 8. Pediatric Clinic, University of Milan. 9. were Caucasian origin, 17% Asian, 16% others. 51 patients had received a kidney 4Nephrology, dia transplant. Bambino Gesù Children Research Hospital , Piazza S. Onofrio 4 , 00165 Rome , Italy Median age at onset of symptoms was 10 months; median age of diagnosis was 1.5 years. The duration between onset of symptoms and diagnosis has fallen from 8.8 months in 1998 The term “Full-house nephropathy” (FHN) describes a group of glomerular lesions with to 5.8 months in 2004. diffuse positivity by immunofluorescence for IgA, IgM, IgG, C3 and C1q, similarly to lupus Longitudinal data on renal function (in pre-transplant patients) is available for analysis. 68 nephritis (LN), but without evidence of SLE and/or circulating autoantibodies. patients commenced cysteamine < 2 years of age. Whereas 90% historical untreated Herein, we present the results of a retrospective Italian multicentric pediatric study. controls had a plasma creatinine > 310µmol/l at age 12y, only 6 of 25 (24%) children in the Altogether, 40 FHN and 145 LN cases have been collected and analyzed. UK registry who started treatment under 2 years had a creatinine over this value at 12y. The female prevalence was 42% in FHN and 80% in LN. The mean age of onset was Fourteen of 35 (40%) who started treatment after 2 years and reached 8y age, had a similar (11-12 years). creatinine < 310µmol/l compared to 50% historical untreated controls. Classification of glomerular lesions in FHN was as follows: mesangial glomerulopathy The median dose of cysteamine, in 2004 was 1.0 grams/m2/day. (33mg/kg/day). This large (GN) 17.5%, focal GN 15%, diffuse proliferative GN 47.5% and membranous GN 20%. registry suggests that early (start <2y) cysteamine treatment is associated with preservation Immunofluorescence analysis of skin biopsy specimens in 23 LN and 15 FHN showed of renal function and that later treatment is less effective. Data on cystine depletion is under immune deposits in 74% of LN and 40% of FHN. analysis. Improved efficacy may follow if the prescribed dose were higher (recommended At the onset of the disease, 87% of patients with FHN had normal renal function and 65 % dose 60mg/kg/day; 1.3gm/m2/day). had nephrotic syndrome. All patients were treated with steroids and/or immunosuppressive drugs. After a mean follow-up of 4.6 years, 40% had stopped all medications; 92% had (The Registry receives funding support from Orphan Europe, distributors of cysteamine.) normal renal function, 78% had low-grade proteinuria and 22% had no proteinuria. No relapse of renal disease was documented. These results were significantly better then those of the LN group. After a mean follow-up of 5.8 years, 8/40 patients had developed SLE. We conclude that FHN has a better prognosis then LN, but that approximately 20% of patients developed SLE with time, indicating the need for a long term follow-up of these patients. 1516 Pediatr Nephrol (2006) 21:1493–1635

COD. OP 37 COD. OP 38 SERUM AND URINARY LEVELS OF INTERLEUKIN-6 IN Variable phenotype and evolution in children with TCF2/HNF-1beta CHILDREN WITH HENOCH-SCHOENLEIN PURPURA nephropathies JS Lee, JI Shin, MJ Kwon Department of Pediatrics and the Institute of Kidney Disease, S Decramer, F Bandin, F Bouissou, C Bellanne-Chantelot. Yonsei University College of Medicine, Seoul, Korea Department of Pediatrics, Yeoncheon Paediatric nephrology , Hôpital des Enfants 330 av de grande Bretagne , 31059 toulouse , County Hospital, Kyunggi, Korea France Yonsei University College of Medicine , Department of Pediatrics, 134 Shinchon-Dong, Seodaemun-Ku, C.P.O. Box 8044 , 120-752 Seoul , South Korea Hepatocyte nuclear factor-1 beta, encoded by TCF2 gene, is responsible for MODY-5 and restricted renal phenotypes in children. Background: Interleukin 6 (IL-6) has various biological functions involved in the immune We describe a monocentric cohort of 21 paediatric patients with TCF2 gene anomalies. or inflammatory responses. To elucidate the role of IL-6 in the pathogenesis of Henoch- Prenatal diagnosis revealed the presence of both hyperechogenic- and multicystic kidneys. Schoenlein purpura (HSP). 50% of the patients had, mainly cortical, cysts while the mean prenatal renal length was Methods: We measured the serum and urinary levels of IL-6 in 30 patients with HSP, 18 +0,5±0,3 SD. with HSP nephritis (HSPN), and 10 normal children using enzyme-linked immunosorbent After birth, renal growth was impaired with a mean postnatal renal size of –1,6 ± 0,7 SD. In assay (ELISA). patients with a solitary kidney there was no compensatory hypertrophy. Cysts appeared Methods: Serum IL-6 levels in HSP and HSPN patients (36.03 ± 87.56 and 32.68 ± 71.59 bilaterally in all patients but two. After a mean follow-up of 74 months, 19 children pg/ml, respectively) were significantly higher than in normal controls (3.17 ± 3.78 pg/ml) (p developed bilateral nephropathies and 2 developed unilateral multicystic kidney disease. 10 < 0.05). Urinary IL-6 levels in HSPN patients (62.23 ± 73.53 pg/ml) were significantly children had normal renal function (CrCl>70mL/min/SC), 7 moderate (CrCl between 70 higher than in HSP patients and normal controls (9.05 ± 8.35 and 5.83 ± 5.62 pg/ml, and 40) and 4 severe renal insufficiency (<40) with terminal renal failure at 42 months for respectively) (p < 0.05). In 13 HSPN patients with proteinuria, urinary IL-6 levels one patient. correlated positively with the 24 hour urinary protein/creatinine ratio (urinary IL-6 = 51.923 Extrarenal manifestations included 3 cases of diabetes (one at the age of 13 post x 24 hr protein/cr – 45.091, r2 = 0.619, p = 0.001). However, urinary IL-6 levels did not transplantation), ten with early hyperuricemia, 4 with cholestasis, 1 with exocrine pancreatic correlate with the serum IL-6 levels. insufficiency with low faecal elastase and 1 with pancreatic hypoplasia without clinical Conclusions: These results suggest that IL-6 may play a role as a mediator of inflammation symptoms. in HSP, and be implicated in the development of mesangial inflammation and glomerula r The main TCF2 gene anomaly was a complete heterozygous deletion (M1_W557del, 15/21 damage in HSPN. patients). We found 6 point mutations (3 G76C, IVS6+1G>A, Q253P, N289D). For the 3 patients with G76C mutation, 2 had unilateral MCKD and 1 bilateral severe renal cystic hypoplasia leading to severe renal dysfunction. Half of the genetic anomalies appeared de novo. TCF2 gene anomalies are associated with variable post-natal renal phenotype, function and evolution.

COD. OP 39 COD. OP 40 An ancestral activating RET mutation is associated with renal Identification of entire LMX1B gene deletions in nail patella syndrome: hypodysplasia final evidence for haploinsufficiency as the main pathogenic mechanism 1Rémi Salomon, 1Vincent Morinière, 2Massimo Santoro, 3Emmanuelle Génin, 4Elke underlying dominant inheritance in man Wühl, 5Klaus-Eugen Bonzel, 6Dorota Drozdz, 7Mieczyslaw Litwin, 8Amira Peco-Antic, EMHF Bongers, IJ de Wijs, E Levtchenko, C Marcelis, LH Hoefsloot, NVAM Knoers 9Simone Wygoda, 4Franz Schaefer, 1Corinne Antignac and ESCAPE Trial Group 1 Presenting author: EMHF Bongers Affiliation: Department of Human Genetics, Radboud INSERM U574, Hôpital Necker Enfants Malades, Université René Descartes, Paris, France. University Nijmegen Medical Centre, The Netherlands 2 Dipartimento di Biologia e Patologia Cellulare e Molecolare, Universita di Napoli Department of Human Genetics, Radboud University Nijmegen Medical Centre , P.O. Box Federico II, Napoli, Italy. 3 INSERM U535, Villejuif, France. 4 Pediatric Nephrology, 9101 , 6500 HB Nijmegen , The Netherlands University Children’s Hospital Heidelberg, Germany 5 University Hospital Essen, Germany 6 Jagiellonian University Medical College, Krakow, Poland 7 Children`s Memorial Health Nail patella syndrome (NPS) is an autosomal dominant disorder characterized by nail and Hospital, Warsaw, Poland 8 University-Children’s Hospital Belgrade, Yugoslavia 9 Urban skeletal malformations, nephropathy, and glaucoma caused by mutations in the transcription Hospital St. Georg, Leipzig, Germany Presenting author: R Salomon factor LMX1B. Glomerular podocytes from Lmx1b-/- mice reveal aberrant foot processes Université René Descartes , Hôpital Necker 149, rue de Sèvres , 75015 Paris , France and slit diaphragm formation. It is as yet unclear why heterozygous LMX1B mutations cause NPS nephropathy in humans, whereas Lmx1b+/- mice develop no renal symptoms. The RET receptor, its ligand GDNF and its co-receptor GFRA1 play a pivotal role during The hypothesis that haploinsufficiency is the main mechanism underlying dominant the early phases of nephrogenesis and in enteric nervous development, as assessed by the inheritance in human NPS is based on the fact that the same phenotypic variability is observation of severe renal hypodysplasia and intestinal aganglionosis when one component observed in individuals with LMX1B missense, nonsense, frameshift or splice-site of this complex is mutated in mice. In humans, loss-of-function RET mutations have been mutations and that the range and severity of symptoms varies both within and between reported in Hirschsprung disease and activating mutations are implicated in multiple families. This assumption is supported by the lack of any dominant-negative effect observed endocrine neoplasia 2A (MEN2A), but genetic abnormalities have not been described to by in vitro-experiments studying missense and truncation LMX1B mutations. By MLPA date in patients with renal malformations. We analyzed the genes of the analysis with specific probes for the different exons 1-8 of LMX1B, we found a deletion of RET/GDNF/GFRA1 complex in a cohort of 99 children with renal hypo/dysplasia (RHD). the entire gene in two unrelated individuals and a deletion of exons 3-8 in another patient A single mutation (Y791F) was found in the RET proto-oncogene in six unrelated patients. from 15 classic NPS families (3/15; 38%) in which no mutation could be detected by Since this mutation is known to predispose to medullary thyroid cancer (MTC), we sequencing LMX1B. screened for thyroidal abnormalities and found elevated baseline calcitonin levels and This first identification of entire LMX1B deletions strongly confirms the hypothesis that sonographic alterations in one patient and his mutation carrying father. We demonstrated by haploinsufficiency is the principal pathogenic mechanism of NPS. The fact that NPS in vitro functional studies that this mutation activates the RET tyrosine kinase domain, but nephropathy is observed in individuals with heterozygous deficiency of LMX1B and to a lesser degree than the C634 mutation more commonly associated with MEN2A. resembles a milder variant of kidney disease in Lmx1b-/- mice, whereas Lmx1b+/- mice are Haplotype analyses at the RET locus indicate that the Y791F mutation was inherited by the phenotypically normal, supports the assumption that a difference in dosage sensivity for this six subjects from a common ancestor who lived approximately 26 generations ago. Taken gene emerge in the two species. together these findings suggest that the Y791F mutation predisposes not only to MTC but also to RHD, with a low penetrance for both diseases. Pediatr Nephrol (2006) 21:1493–1635 1517

COD. OP 41 COD. OP 42 Insulinsensitivity and beta-cell function in children with idiopathic MDR-1 GENOTYPE AND TIME TO REMISSION ON ORAL nephrotic syndrome PREDNISONE IN CHILDHOOD STEROID SENSITIVE M Tkaczyk, A Czupryniak, J Lukamowicz E Ksiàýek, A Póùtorak-Krawczyk, E NEPHROTIC SYNDROME Úwiàtkowska, M Nowicki 1 Dept. of Nephrology and Dialysis; 2 Laboratory Dept.Polish A Wasilewska, W Zoch-Zwierz, G Zalewski, L Chyczewski Mother`s Memorial Research Institute, Ùódê, Poland I Department of Paediatrics, Medical University in Biaùystok, Poland , Waszyngtona 17 , Dept of Nephrology and Dialysis, Polish Mother`s Memorial Research Institute , 281/289 15-274 Biaùystok , Poland Rzgowska St , 93-338 Ùódê , Poland Steroid sensitive nephrotic syndrome (SSNS) in children tend to differ in terms of treatment Glucose intolerance which is frequently found in patients with the idiopathic nephrotic responsiveness and course of disease. P-glicoprotein (P-gp), a product of MDR1 gene, is an syndrome (INS) may be linked to an increased cardiovascular risk. Recently it has been efflux pump contributing to prednisone intestine absorption and bioavailability. suggested that proteinuria and steroid treatment may affect insulin sensitivity. The aim of The study was undertaken to investigate associations of MDR1 genetic polymorphisms the study was to assess insulin resistance (IR) and â-cell function in children with INS at (C1236T, G2677TA, C3435T) and three - marker haplotypes with parameters describing various stages of the disease. The study group comprised 66 children (32 male, 34 female; clinical course and treatment response of childhood SSNS. Material and methods: Three age 8.1 ± 5.0 years). 20 healthy, sex- and age-matched subjects served as controls. The MDR1 genetic markers were analysed in 108 children diagnosed with SRNS and 115 study group was divided into 3 subgroups: A (n=24) children in relapse of INS (steroids 60 healthy controls of Podlasie region. All subjects were genotyped using PCR-RFLP method. mg/m2/48h; proteinuria 1.02±1.04 g/dl); B (n=20) in remission treated with steroids (30 EM algorithm. Results: There was no difference in genotypic and allelic distribution in mg/m2/48h); C (n=22) in remission but without steroids. Fasting glucose and insulin levels SSNS and healthy children. However all individual polymorphisms were strongly were measured to calculate insulin resistance (HOMA-IR) and beta-cell function (HOMA- associated with time to response to initial prednisone therapy. Frequencies of mutated beta) using Homeostatic Model Assessment. Fasting glucose was within normal range in all alleles were higher in late (time to remission >7 days, n= 74) oral prednisone responders subjects. HOMA-IR was significantly higher in group A (3.2±3.3) and group B (2.4±1.7) (0.53, 0.52, 0.66) as compared to early (time to remission <7 days, n = 34) responders (0.24, than in group C (1.45±1.6 and controls (1.12±0.6) (p<0.05). HOMA-beta was significantly P= 0.0001; 0.19, P=0.00001; 0.32, P=0.00001, respectively for positions 1236, 2677 and higher in group A and B than in C and controls (p<0.05). In multivariate analysis HOMA- 3435). Odds ratios (ORs) reflecting strength of associations were as follows: 6.79 (95% IR correlated with proteinuria (â=0.45, p<0.001), steroid dose (â=0.32) and BMI (â=0.42). CI:1.96- 23.54) for 1236 T/T, 13.7 (95% CI:2.78 – 67) for 2677 T/T and 9.92 (95% CI: In conclusion, an increase in insulin resistance with compensatory enhanced â-cell secretion 3.01-32.71) for 3435 T/T as compared to respective wild type homozygotes. Because of is a typical finding in children with INS treated with steroids. Proteinuria seems to be an strong linkage disequilibrium between the markers, T/T/T haplotype was similarly found to independent risk factor for decreased insulin sensivity. be significantly associated with late oral steroid response (0.50 vs 0.19, p= 0.0003). The study was supported by 2P05E03426 grant of the Polish Ministry of Science. Conclusions: The variants of MDR1 may be associated with increased expression of P-gp in target tissues, what may be responsible for late response to prednisone.

COD. OP 43 COD. OP 44 METHYLENTETRAHYDROFOLATE REDUCTASE (MTHFR) Complete remission of infantile nephrotic syndrome associated with 677C-T GENE POLYMORPHISM AND PROGRESSION OF Coenzyme Q10 deficiency after CoQ10 supplementation. STEROID-RESISTANT NEPHROTIC SYNDROME IN CHILDREN G Montini, C Malaventura, L Salviati, C Carasi, L Murer, G Zacchello L Prikhodina*1, N Poltavets2, E Zaklyazminskaya2, N Galeeva2, S Tverskay2, A Nephrology Dialysis and Transplant Unit , Pediatric Departement , 35128 Padova , Italy Polykov2, V Dlin1, M Ignatova1 1Institute of Pediatrics & Children Surgery, 2Research Center for Medical Genetics. Infantile nephrotic syndrome (INS) is usually a steroid resistant condition, with different Institute of Pediatrics & Children Surgery , Nephrology Department , 125412 Moscow , genetic backgrounds. Russia We describe a familial case whose clinical picture was a typical nephrotic syndrome, which effectively responded to oral CoQ10 supplementation. The patient is the second child The MTHFR 677 C-T gene polymorphism is associated with hyperhomocysteinaemia an (female) of first cousins of North African origin. In the older brother (kidney transplant independent cardiac risk factor in patients with chronic renal failure (ÑRF). The study was because of a steroid resistant NS developed when the child was 12 months old, serious conducted to determine the association of the MTHFR 677 C-T genotype with progression neurologic symptoms when the child was 18 months old) a documented form of CoQ10 of steroid-resistant nephrotic syndrome (SRNS) in Russian children. deficiency (decreased concentration of CoQ10 in muscle and fibroblast extracts) was The MTHFR 677 C-T polymorphism of 29 children (15M/14F; age 13.1±0.8 years) with diagnosed. A homozygous missense mutation in the COQ2 gene was later identified in both primary SRNS and 50 healthy individuals was investigated using restriction fragment length patients. polymorphism analysis. Renal biopsy in SRNS patients revealed mesangial proliferative The girl developed a typical NS (proteinuria 500 mg/Kg/day), oedema, mild acute renal glomerulonephritis (GN) (n=12), membranoproliferative GN (n=8), FSGS (n=7) and failure (plasma creatinine 125 umol/L). A kidney biopsy was performed showing pedicle membranous nephropathy (n=2). fusion and a very high number of mithocondria at the electron microscopy in the podocytes. Allele frequencies of 677 C-T polymorphisms of the MTHFR gene in SRNS patients and CoQ10 supplementation (30mg/Kg/day) was immediately started with resolution of the NS controls were identical: 0.76/0.24. The distribution of the MTHFR 677 C-T genotypes was in 20 days. Proteinuria persisted in the range of 0.5-1 g/day for 12 months and then almost not different significantly between children with SRNS and controls (C/C:C/T: completely disappeared. After a follow up of 26 months renal function is normal, T/T=62:28:10 (%) vs. 56:40:4 (%), respectively). The results of the MTHFR 677 C-T proteinuria is 0.22 g/day and no neurologic symptoms developed. genotypes distribution among SRNS patients are shown in the table. To the best of our knowledge this is the first report of a CoQ10 sensitive NS. No steroids Homozygosity of C/C and T/T the MTHFR 677 C-T gene polymorphism are associated were used in this patient. In infants with early onset NS and electron microscopic evidence with increased risk for development of CRF in children with SRNS. These findings suggest of mithocondrial involvement, this new entity has to be taken into consideration, as early that the MTHFR 677 C-T gene polymorphism may be one of genetic factors for progression treatment with CoQ10 has been demonstrated to be effective. of SRNS in children. 1518 Pediatr Nephrol (2006) 21:1493–1635

COD. OP 45 COD. OP 46 PHARMACOLOGICAL INHIBITION OF p-ANCA ACTIVATED Plasma homocysteine and albumin homocysteinylation in children with INTRACELLULAR SIGNALLING IN POLYMORPHONUCLEATED idiopathic nephrotic syndrome LEUKOCYTES A Czupryniak(1), M Tkaczyk(1), G Chwatko(2), E Ksiàýek(1), E Bald(2), M Nowicki(1) °S Balegno, °M Chiesa, °L Peruzzi, °A Amor e, °D Mancuso, °D Manniello, §G Gregorini, (1)Dept. of Nephrology and Dialysis, Polish Mother’s Memorial Research Institute, Lodz, *M Ricotti, *PA Tovo, °R Coppo °Nephrology, Dialysis and Transplant Unit, Regina Poland (2)Dept of Environmental Chemistry, University of Lodz, Poland Margherita Children Hospital ; *Chair of Pediatry University of Turin; § Nephrology Unit, , FREDRY 31 , 95-020 ANDRESPOL , Polan d Ospedali Civili, Brescia Nephrology, Dialysis and Transplant Unit, Regina Margherita Children Hospital , Piazz a Hyperhomocysteinemia is an independent risk factor for cardiovascular disease but the Polonia, 94 , 10126 Turin , Italy exact mechanism of homocysteine (Hcy) toxicity is not clear. Recently, protein homocysteinylation has been suggested as a possible link between elevated plasma Hcy and ANCA represent a key marker of vasculitis, although their mechanism of action is mostly vascular injury. Little is known on the relation of plasma Hcy level with the extent of unknown. protein homocysteinylation in children with NS. Aim of this study were a) to evaluate the role of ANCA in the activation of cytoplasmatic The aim of the study was to assess total and protein bound Hcy (tHcy and pHcy) levels in signalling (Akt pathway) and transcriptional activity (NF-kB) in neutrophils (PMN) of children with idiopathic NS at various stages of the disease. healthy subjects previously primed with TNF- and b) to investigate the effect of an anti- The study group comprised 49 children (19 M, 30 F; aged 8,1±5,0 years). 20 healthy, retroviral drug Saquinavir (Saq) inhibitor of proteasomic activity, on such mechanisms. gender- and age-matched subjects served as controls. The study group was divided into 3 Serum IgG of 9 p-ANCA patients (IgG-ANCA) and 5 control subjects (IgG-C) were subgroups: A (n=21) children at the onset of NS relapse (steroids 60 mg/m2/48h; isolated by affinity chromatography on protein A column. Firstly, PMN were primed with proteinuria 1.02±1.04 g/dl); B (n=17) - patients at the onset of remission treated with TNF- and then exposed to IgG-ANCA or IgG-C to evaluate a time-dependent effect. steroids (30 mg/m2/48h); C (n=11) - patients in remission with no steroid treatment. tHcy Afterwards, PMN were treated with Saq and then exposed to TNF- and to IgG-ANCA o r and pHcy as well as serum albumin and lipid profile were assessed in all subjects. Albumin IgG-C. Nuclear and cytoplasmatic extracts were collected. The nuclear binding of NF-kB homocysteinylation was calculated as pHcy per 1 g of albumin. Plasma Hcy was assessed resulted significantly increased after 15 minutes of priming with TNF-. PMN primed with with HPLC method (Hewlett Packard, Waldbronn, Germany).The results are presented in TNF- showed an activation of the Akt signalling, detected by an increased the table. phosphorylation of Akt (p-Akt). The p-Akt/Akt ratio increased significantly more in PMN In conclusion, tHcy in nephrotic syndrome is similar to the levels found in healthy subjects. exposed to IgG-ANCA than in those exposed to IgG-C (p<0.01). The pre-treatment with However, albumin homocysteinylation is significantly more pronounced during NS relapse. Saq induced a significant inhibition of Akt phosphorylation, with decrease in pAkt/Akt ratio Supported by grant of the Polish Ministry of Science nr 2P05E3426. (p<0.01), see table

In conclusion, our data suggest a key role of the Akt system in ANCA signalling. O f interest is the in vitro modulation obtained by an anti-retroviral drug, with proteasome inhibitor activity.

COD. OP 47 COD. OP 48 THE ASSOCIATION OF MEMBRANOUS ADVANCED OXIDATION PROTEIN PRODUCTS (AOPP) AND GLOMERULONEPHRITIS AND FULL HOUSE DEGALACTOSYLATED IgA1 IN PATIENTS WITH IgA IMMUNOFLUORESCENCE PATTERN INDICATES A LUPUS NEPHROPATHY (IgA N): A PROSPECTIVE DUBLE BLIND NEPHRITIS RANDOMIZED PLACEBO CONTROLLED TRIAL WITH ACE M Caropreso1, F Nuzzi1, G Malgieri1, M D`Armiento2, AVS Ferretti1, F D`Angelo1, L INHIBITORS Marzano1, R D`Arcangelo1, C Pecoraro1 Department of NephroUrology, Santobono *A Amore, *L Peruzzi, *S Balegno, *L Bertola, *F Magnetti, *R Camilla, *G Conti *D Children`s Hospital, Naples, Italy Mancuso, °G Lama, °M Giani, °GB Capasso, °G Lavoratti, °A Gianviti, °D.Weitzel, R Santobono Children`s Hospital , Department of NephroUrology, via Mario Fiore n°6 , Coppo. * Nephrology, Dialysis and Transplant Unit, Regina Margherita Children Hospital, 80129 Naples , Italy Turin, Italy °for the Collaborative Study IgACE , Biomed BMH4-97-2487 Nephrology, Dialysis and Transplant Unit, Regina Margherita Children Hospital , Piazza Membranous glomerulonephritis (MGN) is characterized by thickening of the glomeruler Polonia, 94 , 10126 Turin , Italy basement membrane due to the presence of subepithelial immune deposits. From a morphological point of view, idiopathic MGN is indistinguishable from class V lupus Aberrantly glycosylated IgA1(deGal-IgA1) have been detected in IgAN patients. Oxidative nephritis (LN) . We evaluated clinical and pathologic features of 33 patients, 20M/13F, stress has recently been suggested to play a role in IgAN, as indicated by the detection of mean age 10.2 years (3.9-16.8), mean age at onset 8.8 years (3.1-15.4), with MGN without high AOPP serum levels in patients with progressive IgAN. Aim of this study was to other serologic and clinical signs of SLE at biopsy time. Nephrotic Syndrome (NS) was investigate the levels of AOPP and of aberrantly glycosytaled IgA1 (deGal-IgA1) in sera of present in 31/33 patients, a non-nephrotic proteinuria in 2/33; the characteristic MG children and young IgAN patients with stable proteinuria (1-3.5 g/1.73m2/day) and normal immunofluorescence pattern showed in 11/33 a full-house nephropathy (FHN): IgA, IgG, GFR (>60 ml/min/1.73m2), enrolled in a prospective double-blind placebo-controlled trial IgM, C1q, C3 simultaneous deposits; the follow-up mean time was 3.6 years (range 1.2- and randomized to receive Benazepril (ACE-I) or placebo (PL). Negative outcome was 30% 6.1). Patients with NS received renal biopsy within 6 months from disease onset because of decreasing of basal GFR and/or developing proteinuria 3.5 g/1.73m2/day; positive cortico-resistance/dependance. After 1.8 year mean time (range 0.8-2.3) from the disease outcome was proteinuria remission (<0.5g/1.73m2/day). Urinary samples of 43 patients (19 onset 3/33 (10%) patients developed clinical and serologic features of SLE: all had an ACE-I, 24 PL) with mean follow-up of 42 months, were available. In basal conditions, the immunofluorescence pattern of FHN.The FH immunofluorescent pattern, cytoplasmic values of AOPP (measured by spectrophotometry) and deGal-IgA1 (assessed as binding o f tubuloreticular inclusions on electron microscopy and membranous nephropathy with IgA1 isolated by affinity chromatography on Jacalin–Sepharose to Vicia Villosa, VV and mesangial deposits are tipical features of LN. At the moment in the remaining 8 patients Helix Aspersa, HAS) were significantly high (p<0.001). During the follow-up both the evidence of SLE is absent and a six monthly clinical and laboratory monitoring is planned ACE-I and PL showed a significant decrease of AOPP (p=0.001) and deGal-IgA1 levels looking for SLE features. (ACE-I: HAS p<0.0001, VV p<0.073; PL: HAS p<0.007, VV p<0.011). Comparing the Our experience suggests that a MGN associated with a FH immunofluorescence pattern can clinical course of the patients, we evidenced that only the ACE-I with favourable clinical be considered a true Lupus Nephritis. course showed a conversion to normal values of AOPP while the reduction of deGal-IgA1 was not correlated to outcome. These data indicate that the beneficial effects of ACE-I in moderately proteinuric IgAN are more related to the reduction of the oxidative stress than to the deGal-IgA1 modulation. Pediatr Nephrol (2006) 21:1493–1635 1519

COD. OP 49 COD. OP 50 LONG-TERM CYCLOSPORINE A TREATMENT FOR FOCAL AND Screening For Prevalence Studies of Hypercalciuria Among SEGMENTARY GLOMERULOSCLEROSIS IN CHILDREN. Schoolchildren: Is One Spot Urine Sample Enough? A Tsygin, O Komarova, A Sukhanov, Research Centre for Child Health, Moscow S Akman* 1 , M Koyun 1, A Gür Güven 1, S Filiz 1, H Akbas 2, YE Baysal 1, M Gültekin Research Centre for Child Health , Pediatric Nephrology, Lomonosovsky pr. 2/62 , 119991 2, N Dedeoglu 3 1Department of Pediatric Nephrology, Akdeniz University, Medical Moscow , Russia Faculty, Antalya, Turkey 2Department of Biochemistry, Akdeniz University, Medical Faculty, Antalya, Turkey 3Department of Public Health, Akdeniz University, Medical Twenty one children aged 1,5-16 years with non-familial biopsy-proven steroid-resistant Faculty, Antalya, Turkey focal and segmentary glomerulosclerosis (FSGS) were treated with Cyclosporine A (CsA) , Akdeniz University, Medical Faculty, Department of Pediatric Nephrology , 07070 3,2-7,6 mg/kg as initial dosage, oral prednisolone 1,5 mg/kg every other day tapered to the Antalya , Turkey 12-th month and methylprednisolone pulses (MP) 20-30 mg/kg every other day for the first 2-4 weeks in 14 of patients. The duration of the disease before treatment was from 6 months to 7 years. The researchers almost always prefer one urine sample on prevalence studies of After 6 months of treatment f complete remission of proteinuria was in 8 (38%) of children, hypercalciuria. The aim of this study was to determine the prevalence of hypercalciuria by partial remission in 5 (24%), more than 2-fold decrease of proteinuria in 2 (10%), no effect double urine samples and to compare the results of one spot urine and double urine samples – in 6 (28%) including one patient achieved ESRD. After one year of treatment a complete among school-aged children in Antalya, southern Turkey. remission observed in 11 (52%), partial remission in 4(19%), decrease of proteinuria in1 Non-fasting, second morning urine samples were collected from 2143 children, who were (5%) and no effect in 5(24%). In all of non-responders CsA was discontinued. Eventually 3 selected by systemic randomization method from 14 schools located in different parts of the of non-responders turned into ESRD. The better response was in patients with shorter city. Suspected hypercalciuria was defined as urinary calcium/ creatinine ratio (UCa/Cr) disease duration and less severe disease. higher than or equal to 0.21 (mg/mg). In children with suspected hypercalciuria, 24-hour MP pulses were not used in 7 of patients because of less severe disease or contraindications. urine samples or for the second time non-fasting spot urine samples were collected. However, 6 of them demonstrated a good response to treatment. None of responders had Children with daily urinary calcium excretionQQ 4 mg/kg/day or UCa/Cr 0.21 on two any severe side effects of CsA. consecutive urine samples were considered as hypercalciuric. We conclude that early and prolonged treatment with CsA can cause a complete or partial A total of 2143 children, 1161 boys (54.2%) and 982 girls, aged 6-14 years (mean 10.25 ± remission of proteinuria in about 70% of patients with idiopathic FSGS. 2.36 years), were included in the study. 269(12.5%) and 66 (3.1%) of children had suspected and definite hypercalciuria, respectively. There was a weak correlation between spot UCa/Cr ratios and daily urinary calcium excretions in children with UCa/CrQ 0.21 (r=0.27, p<0.05). The prevalence of hypercalciuria, confirmed with 24-hour or double consecutive spot urine samples, in our study population was 3.1%, which was one-fourth of the level if only one spot urine sample would have been used. The screening by one spot urine sample may be misleading in prevalence studies. Although it is troublesome to obtain two consecutive urine samples, it is necessary for reliable results in studies regarding hypercalciuria.

COD. OP 51 COD. OP 52 SMALL FOR GESTATIONAL AGE BIRTH AND RISK OF Cross-sectional analysis of urinary biomarkers excretion in children HYPERTENSION IN ADULT LIFE: TWO UNRECOGNIZED with chronic kidney disease and different underlying renal pathology. CHILDREN POPULATIONS? R Grenda 1, M Litwin 1, R Janas 1, E Sladowska 1, E Wuehl 2, O Mehls 2, F Schaefer 2 C De Felice 1 M Strambi 4 B De Capua 2 R Tassi 3 D Costantini 2 S Schiavone 4 E and ESCAPE Trial Group 1 Children`s Memorial Health Institute, Warsaw, Poland 2 Scalacci 4 G Chitano 5,6 G Latini 7,8 Presenting Autor: Mirella Strambi University of Heidelberg, Germany Department of Pediatric, Obstetric and reproductive medicine , University of Siena, Viale Children`s Memorial Health Institute , Dept. of Nephrology&Kidney Transplantation , 04- Bracci 36, , 53100 Siena, , ITALY Ital y 730 Warsaw , Poland

BACKGROUND: Clinical and experimental evidence indicates a link between small size at Chronic kidney disease (CKD) may influence the urinary excretion of various biomarkers. birth and cardiovascular risk in adult life. Relationship with hypertension remains Aim of interim analysis was to evaluate, if specific underlying renal diseases determine the controversial, although SGA children with a reduced day-night physiological variations are value of urinary excretion of endothelin-1 (ET-1), transforming growth factor beta considered to be at risk of developing hypertension. AIM: Evaluation of physiological (TGFbeta) and vascular edothelial growth factor (VEGF165). Patients: overall 319 children day/night variations of BP in two subgroups of children as a function of posterior with CKD (mean GFR 48,5 +/-22 ml/min/1.73m2), at mean age of 11.5+/-3.9 y. and 101 communicating arteries (PCoAs) of circle of Willis. METHODS: 26 randomly selected age-matched healthy controls. Methods: values of urine ET-1, TGFbeta and VEGF165 were children born SGA participated to the study (age at examination, M ± SD: 9.45 ± 2.08 yr). evaluated with RIA-based techniques.The results were adjusted to 1 g of urine creatinine. ABPM was carried out in all children; population was subdivided into two groups, based on Results: urinary excretion of all 3 biomarkers was significantly (p<0.0001) higher in transcranial doppler evidence of bilateral non-functioning PcoAs. Percentage of day-to- patients, compared to controls (874+/-1656 vs 215+/-335 fmol/g for ET-1; 269+/-359 vs night variations in systolic (SBP), diastolic (DBP) and mean (MBP) BP were the main 155+/-158 ng/g for VEGF and 35,7+/-46.8 vs 10.9+/-9.8 ng/g for TGFbeta). There was a outcome measures. RESULTS: 17 (65.4%) children were found to be PcoA-positive vs. 9 negative correlation of all biomarkers urine excretion with age and GFR, while no (34.6%) bil-PCoA-negative. Groups were comparable for BP percentiles for age, gender, correlation with proteinuria. The highest urine excretion of ET-1 and TGFbeta was seen in gestational age, birth weight SDS, auxometric growth (p³ 0.35). PcoA-positive children obstructive nephropathy. Summary: CKD is reflected by increased urinary excretion of ET- showed significantly reduced day-night variations in SBP (7.16 ± 4.93% vs. 16.6 ± 5.55%, 1,TGFbeta and VEGF165, with specific relations to age, GFR and primary renal disease. p= 0,0002), DBP (14.28 ± 8.92% vs. 24.96 ± 7.62%, p=0.0056 ) and MBP (9.84± 8.49% vs. 21.2 ± 7.31%, p=0.0024), had a significantly higher frequency of pregnancy-induced hypertension ( 64.7% vs. 11.1% , p= 0.0144), and mothers showed a significantly increased right-side carotid intima-media thickness (0.661 ± 0.209 vs. 0.481 ± 0.126 mm, p=0.0277). CONCLUSION: Our data suggest the existence of two phenotypically distinct SGA children populations, at possibly different risk of developing hypertension. 1520 Pediatr Nephrol (2006) 21:1493–1635

COD. OP 53 COD. OP 54 Urinary excretion of MMP-9 and collagen IV is a marker of renal Correction of anemia in uremic rats by intramuscular injection of fibrosis in children with CKD lentivirus carrying an erythropoietin gene L Podracká,K Šebeková, A Heidland Jung Sue Kim, M.D.1(presenting author), Hye Won Park, M.D.2, Tae Keun Oh, M.D.3 Medical School UPJS University Košice , Dept.pediat. , 04066 Kosice , Slovak Republic Department of pediatrics, Cheongju St.Mary’s Hospital1, Department of pediatrics, College of Medicine, Pochon CHA University2, Department of Internal Medicine, Chungbuk The renal fibrosis is a hallmark of CKD and reflects the increased deposition of collagens National University College of Medicine3 (I, III, and IV) within scarred kidneys. Moreover, it is increasingly recognized that fibrosis Department of Pediatrics, Cheongju St.Mary`s Hospital , 589-5, Jujung-dong, Sangdang- results from an imbalance of fibrogenesis and fibrolysis. Thus, decreased proteolytic gu , 360-568 Cheongju , Chungbuk South Korea activity could contribute to deposition of collagen. In a pilot study we aimed to investigate whether urinary excretion of collagen IV and MMP- Anemia is an inevitable consequence of chronic renal failure. A lentivirus carrying 9 reflects the renal fibrosis in children, and, whether these non-invasive laboratory methods erythropoietin (EPO) cDNA was administered to skeletal muscle of uremic rats by partial could be helpful in predicting the progressive course of the disease. Urinary collagen IV and nephrectomy and red blood cell production and serum EPO levels were serially monitored. MMP-9 were measured in 33 children (age: 12.5 ±6.2 years) with CKD (22 GN, 9 TIN, 2 After single intramuscular injection of virus doses of 55 ug of p24 antigen (5x107 infectious others; s-creat=130±180umol/l, GFR=59.8±31 ml/min). Urinary protein excretion averaged units), blood hematocrit levels increased and peaked at 3 weeks (47.8 ± 4.2 %, p < 0.01, 1.3 ± 1.7g/d. Renal biopsy was performed in all subjects. Commercial ELISA kits were n=8) and were maintained for at least 20 weeks (44.9 ± 3.3 %, p < 0.01, n=3), over values used to determine urinary collagen IV and MMP-9 concentrations. Clinical, biochemical of control rats receiving lacZ virus (36.9 ± 4.1 %, n=8; 33.1 ± 3.7 %, n=4), respectively. and histological parameters were correlated and compared with those measured in 20 age- Serum EPO levels of EPO rats also increased and maintained to the end of study (156.3 ± and sex-matched healthy controls. Mean urinary levels of MMP-9 and collagens IV were 3.0 g/dL vs. 63.9 ± 1.7 g/dL of control rats, p < 0.01). A polymerase chain reaction (PCR) significantly higher in patients compared to controls (221 v.s. 47 pg MMP-9/umol creat, p< assay for vector sequence in genomic DNA showed that muscle tissue at the site of injection 0.01, and 20.62 v.s. 2.21 ug collagen IV/umol creat, p< 0.01, respectively). Significant was positive and undetectable in liver, spleen, and kidney. The intramuscular injection o f correlation has been found between u-MMP-9 and proteinuria (r=0.501, p< 0.01) and lentivirus produced highly efficient and sustained EPO secretion in uremic rats, which negative correlation between u-collagen IV and GFR (r=-0.417, p< 0.05). suggest this approach could be effective tools to deliver cytokines and clotting factors in Our preliminary data show that urinary concentrations of collagen IV and MMP-9 are disease model of animals. elevated in association with CKD. However, prospective studies in larger group of patients.

COD. OP 55 COD. OP 56 Symptomatic hypotension during cinacalcet treatment for secondary Dialytic phosphate removal: A relevant endpoint of dialysis dosing in hyperparathyroidism children on chronic PD. J Muscheites, E Drueckler, M Wigger, D Haffner D Borzych(1,2), B Nau(1), CP Schmitt(1), A Zurowska(2), F Schaefer(1) (1)Department of , UKJ Dialyse , 18057 Rostock , Germany Pediatric Nephrology, University of Heidelberg, Germany (2)Department of Pediatric Nephrology, Medical University of Gdansk, Poland Calcimimetics are a promising new treatment for patients suffering from secondary University Children`s Hospital , Im Neuenheimer Feld 150 , 69120 Heidelberg , Germany hyperparathyroidism and increased calcium-phosphate product. They are thought to modulate the calcium-sensing receptor and consecutively decrease parathyroid hormone Although hyperphosphatemia is one of the few established risk factors for cardiovascular levels. Recently it has been shown that cinacalcet affects blood pressure in experimental mortality and morbidity in dialyzed patients, the relationship between PD prescription and uraemia. Here we report an adolescent girl with nephronophthisis leading to end-stage renal dialytic phosphate removal is largely unexplored. disease at age 12. On treatment with calcitriol and calcium-free phosphate binders she We analyzed 56 24h clearance and PET studies performed in 35 children aged 0.1-17 yrs on presented with uncontrolled secondary hyperparathyroidism and recurrent hypercalcemic automated PD with 3-13 night-time exchanges, 998±110 ml/m² fill volume and 6.07±1.96 episodes. She was started on cinacalcet (15 mg/day) and concomitant low-dose calcitriol L/m²/day total dialysate turnover. Twenty-eig ht children had a daytime dwell, and 7 were (0.5µg/day). Within four weeks parathyroid hormone (PTH) levels decreased from anuric. Mean total weekly Kt/V urea was 3.0±1.0. Dialytic phosphate clearance averaged 1117pg/ml to 150pg/ml, and calcium-phosphate product was markedly lowered from 5.52 3.9±1.6 (range 1.8-9.4), urine phosphate clearance 2.4±2.5 (0-10) ml/min/1.73m². Serum to 2.7mmol/l. However, she developed symptomatic arterial hypotension necessitating phosphate ranged from 0.92-2.66 mmol/L. adrenergic drugs during hemodialysis sessions. Known causes for arterial hypotension, e.g. The comparison of subjects with phosphate levels above (n=25) and below the upper cardiac insufficiency, were excluded by echocardiography/angiography. Conclusion: normal limit for age (n=31) revealed significantly lower dialytic phosphate clearances in the Cinacalcet let to a sustained decrease of PTH levels and previously increased Ca x P hyperphosphatemic compared to the normophosphatemic group (3.3±1.2 vs. 4.3±1.8, product in our patient. The observed association between cinacalcet and hypotonic crises p<0.05), whereas urinary phosphate removal did not differ and daily phosphate binder should lead to further investigations. intake was even higher in the hyperphosphatemic patients. The 24h dialytic phosphate clearance was correlated with total dialysate turnover (r=0.64, p<0.0001) and the number of exchanges (r=0.59, p<0.001), but not with the fill volume per dwell. A significantly higher dialytic phosphate clearance was associated with > 6 nighttime exchanges and a total dialysate turnover of > 6 L/m²/day. We conclude that dialytic phosphate clearance is an important determinant of serum phosphate control, which can be substantially modified by PD prescription. Pediatr Nephrol (2006) 21:1493–1635 1521

COD. OP 57 COD. OP 58 PROTEIN COMPOSITION OF PERITONEAL EFFLUENTS (PE) IN Acute regulation of CA-125 expression in human primary mesothelial PEDIATRIC PATIENTS ON CHRONIC PERITONEAL DIALYSIS cells by peritoneal dialysis solutions (CPD) M Hömme, T Hackert*, J Schäfer, F Schaefer, and CP Schmitt University Children´s E Verrina 1, G Candiano 1, L Musante 1 M Bruschi 1, S Mangraviti 3, GM Ghiggeri 1, F Hospital, Division of Pediatric Nephrology, and * University clinic for surgery, 69120 Perfumo 1. 1 Nephrology and Dialysis Unit; 2 General Laboratory, G. Gaslini Children`s Heidelberg Hospital, Genoa, Italy University Children´s Hospital , Im Neuenheimer Feld 150 , 69120 Heidelberg , Germany G. Gaslini Children`s Hospital , Nephrology and Dialysis Department - Largo G. Gaslini, 5 , 16148 Genoa , Italy CA125 dialysate effluent concentration is considered as a surrogate marker for peritoneal mesothelial cell mass, and thus for the biocompatibility of peritoneal dialysis (PD) In this study we performed a quantitative and qualitative analysis of PE protein composition solutions. during two 14-hour daytime dwells, conducted on subsequent days with 7.5% icodextrin To investigate the effect of different PD solutions on CA125 expression, we isolated human (ICO) and 3.86% glucose (GLU) solution. PE samples were taken at 0, 4, 8 and 14 hours primary mesothelial cells (HPMC) from omentum of non-uremic patients, and incubated and assayed for two low MW proteins: beta2-microglobulin by chemiluminescence and them at passage 3-4 with conventional (CAPD®), lactate- and bicarbonate based, double cistatin C by nephelometry. Protein composition was analysed employing proteome chamber solution (BicaVera®, Balance®) and with icodextrin solution (Extraneal®). technology, based on two-dimensional polyacrylamide gel electrophoresis, dual CA125 mRNA expression was measured by Real Time rtPCR, protein abundance in cell fluorochrome labelling, image analysis and mass spectrometry. supernatant by ECLIA, and LDH was determined enzymatically. We studied 10 patients, whose age was 13.0 ± 3.1 years, weight 37.9 ± 17.4 Kg, height o f Conventional but not double chamber PD solution induced cytotoxic effects. In surviving 137.2 ± 23.8 cm, body surface area 1.20 ± 0.39 m2; daytime dwell volume was 596 ± 86 cells conventional solution time dependently reduced mRNA expression of CA125 (6/24 h: ml/m2. 57±4 /18±11% vs. control), but not of other genes, including aquaporin 1. CA125 release in Protein transport kinetics was linear (see Table); slightly higher clearance of b2- the supernatant was low. The effect was only partially reversed at pH 7.4 and not dependent microglobulin (P = 0.09) and cistatin (P = 0.08) was registered during ICO exchanges. on buffer substance (lactate, bicarbonate) or osmolality (mannitol). Double chamber PD Ultrafiltration was similar: 24.3% (ICO) vs 23.0% (GLU) of infused volume. solutions did not modify CA125 expression. Icodextrin induced similar cytotoxicity as Dialysate protein pattern at 14 hours resembled that of serum, without important differences conventional PD fluid and markedly suppressed CA125 expression (24h, mRNA: 10±2%). between ICO and GLU samples, but with high inter-individual variability according to The glucose degradation product 3,4-didesoxyglucoson-3-en dose dependently induced patients’ disease and CPD duration. Overall number of identified proteins increased with cytotoxicity and down regulation of CA125 mRNA in surviving cells. time on CPD, as peritoneal permeability to proteins had progressively increased. In two Conventional PD fluids acutely suppress HPMC CA125 mRNA expression, most likely due focal glomerulosclerosis patients protein pattern was characterised by a wider range of to the high GDP content, whereas double chamber PD solutions preserved cell viability and protein species since the beginning of CPD. CA125 expression. CA125 is not merely a marker of peritoneal mesothelial cell mass but of specific cell function.

COD. OP 59 COD. OP 60 Importance of residual renal function in pediatric chronic peritoneal Mobile Online Telemonitoring (MOT) in Dialyzed Children dialysis patients F Schaefer*, M Mattingley-Scott(1), KH Heckert, C Brummer, M Herweg(1), CP Schmitt S A Bakkaloglu L Sever A Noyan N Aksu S Akman M Ekim A Saygili N Yildiz S Caliskan KfH Kidney Center for Children and Adolescents, Heidelberg, Germany (1) IBM Global O D Kara A Bakkaloglu A Soylu H Alpay F Sonmez F Akal ›n S Erdem F Kardelen Services, Walldorf, Germany Gazi University , Department of Pediatric Nephrology Besevler , 06500 Ankara , Turke y Division of Pediatric Nephrology , INF 151 , 69120 Heidelberg , Germany

Preserving residual renal function (RRF) is very important in both predialysis and dialysis The control of the hydration state is a major challenge in ambulatory dialysis. We assessed a patients. It provides small solute and uremic toxin clearance, maintaining fluid balance, novel telecommunication technology that permits continuous ambulatory monitoring of phosphorus control and shows strong inverse relationships with valvular calcification and blood pressure (BP), heart rate and body weight. Digital scales and oscillometric BP devices cardiac hypertrophy in adult dialysis patients. equipped with bluetooth transponders transmit measurements to a mobile phone, which automatically forwards the data to an internet server. Data can be viewed immediately on a We aimed to evaluate the potential relationship between RRF and cardiac function website. MOT was performed for two- to five-week periods in nine APD, four in-center HD parameters in a large group of pediatric chronic peritoneal dialysis (CPD) patients. 137 and one home HD patient aged 6-18 years. Heart rate, systolic and diastolic BP and body patients aged 13.3±5.0 years and 30 age and sex-matched control subjects were enrolled weight varied at mean intraindividual SDs of 11 min-1 (12.5%), 11 (9%) and 8.4 mmHg into the study. Besides hemogram, serum biochemistry, ferritin and parathormone (PTH) (10.9%) and 0.9 kg (2.4%), respectively. Maximal variations averaged 50 mmHg for levels, echocardiography was performed. Mean systolic and diastolic blood pressures were systolic BP and 3.4 kg for weight. In several instances significant shifts of BP or weight 117±17 and 76±15 mmHg, residual urine 0.9±1.0 ml/kg/h, daily ultrafiltration 587±447 ml, occurred in APD patients, resulting in ad-hoc modifications of dialysis prescription between hemoglobin 9.8±1.8, albumin 3.6±0.5 g/dl, ferritin 391±449 ng/ml and PTH 531±519 the regular outpatient visits. In HD patients the time course of interdialytic weight gain and ng/ml. Lipid parameters were within the acceptable limits. KT/V urea was 2.6±1.0. Systolic, BP was visualized, facilitating the definition of dry weight and BP control. In one patient a diastolic cardiac function parameters were found to be moderately disturbed, left ventricular hypotensive episode following inappropriate post-dialytic nifedipine administration was mass and wall stress were increased. Residual urine was positively correlated with recorded. MOT was well accepted by families and perceived as major relief from the hemoglobin (r=0.217) and KT/V urea (r=0.380) and negatively with blood glucose (r=- responsibility for home dialysis. MOT is an innovative, economical telemedicine concept 0.211) and dialysate glucose concentration (r=-0.353), mean arterial pressure (r=-0.227), utilizing standard bluetooth, mobile phone and internet technology. The planned integration ultrafiltration volume (r=-0.358) and triglyceride (r=-0.187). There were negative of additional medical devices such as PD cyclers will provide complete online surveillance correlations between systolic and diastolic interventricular septal thickness and residual of home dialysis at minimal effort to patients and medical teams. urine (r=-0.211 and r=-0.230, respectively).

It was clearly shown that well preserved RRF is associated with better blood pressure and blood sugar control, less cardiac hypertrophy and less hypertriglyceridemia, acceptable Hb levels and more adequate dialysis in our pediatric CPD patient population. Therefore, preservation of RRF as well as peritoneal membrane are of remarkable importance. 1522 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 1 COD. PP 2 Microarray analysis of human mesangial cell treated by Chinese herbal EFFECTS OF ERYTHROPOIETIN ON OXIDATIVE RENAL medicine INJURY IN RATS WITH CYCLOSPORINE NEPHROTOXICITY Sung-Do Kim, Byoung-Soo Cho B Kasap, A Soylu, F Kuralay, S Sarioglu, M Kiray, K Tugyan, M Turkmen, S Kavukcu East West Kidney Disease Research Institute , Dept. of Pediatric Nephrology, Hoegi-dong, , CamliCay Mah. 5182 Sk. No:112/A Urla , 35315 Izmir , Turkey Dongdaemun-gu, , 130-702 Seoul , South Korea Cyclosporine A (CsA) induces oxidative stress in the kidney. We aimed to evaluate the Magnolia officinalis (MO) is one of the common used-herbs in East Asian countries and is effect of recombinant human erythropoietin (rhEPO) on CsA nephrotoxicity as an prescribed as main component in Saiboku-to. Many studies have demonstrated that it has antioxidant. effect on retarding the progression of chronic glomerulonephritis. However, the molecular effects of MO in cultured human mesangial cell (HMC) have not been defined. We Twenty-one Wistar rats were injected 15 mg/kg CsA subcutaneously and either low dose investigated differential gene expression by MO treatment on cultured HMC according to rhEPO (20 U/kg/d; Group 1, n=7), high dose rhEPO (100 U/kg/d, Group 2, n=7) or saline time sequence. HMC was grown in DMEM with 10% FBS and then MO was treated on (Group 3, n=7) intraperitoneally for 28 days. They were weighed weekly during the study. cultured MC. RNAs of HMC at different time points (4, 8, and 24h after MO treatment and After the last doses, 24-hour urines were collected. Then, rats were sacrificed and blood no treatment) were compared using a cDNA microarray technique. To validate the patterns samples were obtained. Hematocrit, BUN, serum creatinine (Scr), urinary protein/creatinine of gene expression analyzed by the microarrays, some genes were selected and semi- (Upr/cr) and creatinine clearance (CCr) levels were determined in addition to renal quantitative RT-PCR was performed. Among 8,170 genes, 53, 25, and 61 genes were up- superoxide dysmutase (SOD), catalase, glutathione peroxidase (GPX) and thiobarbituric regulated 2-fold above and 36, 19, and 61 genes were down-regulated 2-fold below for 4, 8, acid reactive substance (TBARS) levels representing lipid peroxidation. All the parameters and 24h after MO treatment. We also classified the regulated genes into groups according to were compared between the 3 groups. their changing patterns. We also classified the genes according to the functional group such as apoptosis, signal transduction, immune response, and so on. The present study Body weights were similar in all groups throughout the study. Hematocrit levels were demonstrates profile of gene expression as time goes by after MO treatment on cultured significantly higher in Group 2 (52.012.69, 62.683.43, 36.083.04, respectively; HMC. Gene expression by MO treatment on cultured HMC showed sequential changes. p:0.001). BUN, Scr, Upr/cr and CCr levels were similar between the groups (p>0.05). SOD, Our results provide us much information about gene expression by herbal treatment on catalase and GPX enzyme activity levels were significantly higher in Group 2 (p: 0.019, HMC. Further evaluation of individual genes will be conducted to elucidate molecular p:0.010 and p:0.015, respectively) and TBARS were significantly higher in Group 3 mechanism. (p:0.005).

Regarding the highest antioxidant enzyme levels in Group 2 and the highest oxidation metabolites in Group 3, we may conclude that high dose rhEPO reduces CsA-induced oxidative stress in renal tissue. However, the evident risk of increased hematocrit levels seems to limit the utility of high dose rhEPO.

COD. PP 3 COD. PP 4 EFFECT OF HEAD-OUT WATER IMMERSION ON RESIDUAL CMV infection under calcineurin inhibitor / prednisone and basiliximab KIDNEY FUNCTIONS IN RATS induction therapy in pediatric renal transplant recipients B Kasap, A Soylu, S Sarioglu, F Kuralay, O Yilmaz, M Turkmen,S Kavukcu B Kranz, U Vester, AM Wingen, S Nadalin, A Paul, PF Hoye r , CamliCay Mah. 5182 Sk. No:112/A Urla , 35315 Izmir , Turkey Clinic for Pediatric Nephrology, University Essen , Hufelandstrasse 55 , 45122 Essen , Germany Head-out water immersion (HOI) elevates plasma volume and suppresses peripheral blood pooling. We aimed to determine whether HOI causes glomerular sclerosis by hyperfiltration Newer immunosuppressive drugs (basiliximab, MMF) are reported to be associated with in residual renal tissue or improves renal functions by increasing the renal perfusion in 5/6 better graft survival. The incidence of cytomegalovirus(CMV) infection under these nephrectomized rats. immunosuppressive regimens is of concern and was reported with an incidence up to 40% (Jungraithmayr2003). 5/6 nehrectomy (Nx) or sham operation (Sh) was performed in 10 Wistar rats each. After 10 To evaluate the incidence of CMV infection in children after kidney/liver-kidney days, 5 rats in each group were immersed in water (30-35C) for 1 hour/day for 10 days. transplantation under a restrictive immunosuppression (basiliximab, calcineurin-inhibitor, Four groups were formed [Group1: Sh+HOI(-); Group2: Sh+HOI; Group3: Nx+HOI; prednisone) and a prospective CMV monitoring. The incidence of CMV infection after add Group4: Nx+HOI(-)]. At the end of the immersion period, 24-hour urine samples were on of MMF in a subgroup was analysed. obtained and all animals were sacrificed to obtain blood and kidney tissues. Serum 104 children (mean age 10.6±5.3, follow up 4.1±2.3 years) receiving consecutive 109 creatinine (Scr), creatinine clearance (CCr), urinary volumes and Upr/cr levels, mean kidney or liver-kidney (n=11) transplants were analysed. Primary immunosuppression: glomerulosclerosis score (MGS) and collagen accumulation were determined and compared basiliximab (n=103), cyclosporine A (n=96) or tacrolimus (n=13) and prednisone. MMF between the groups. was added in 23 patients during the first year for various reasons beside acute rejection. CMV infection was defined as the positive detection of pp65, CMV disease as clinical Scr, urinary volumes, Upr/cr, CCr, MGS and collagen accumulation levels were simila r manifestations. Prophylactic CMV immunoglobulin was given to 30 R-/D+recipients. (p<0.05) between Groups 1 and 2. All the parameters were similar in Groups 3 and 4. Scr, CMV infection was detected in 22(20.1%) patients 1.5±1.0 months after transplantation. CCr, MGS and collagen accumulation levels were significantly different between Groups 1 9/22(40.1%) had CMV disease. Acute biopsy proven rejections within the first year and 4 as expected (p:0.036 for each). When Groups 1 and 3 were compared, significant happened in 25/87(28.7%) transplants without CMV and 7/22(31.2%) after a CMV difference in Scr and CCr disappeared while histopathological differences persisted. infection (p=0.08). In 6/23(26.1%) patients treated with MMF CMV infection was detected (odds ratio 1.4) with 4/6(66.7%) showing CMV disease (odds ratio 2.1). Kaplan Meyer HOI caused neither improvement nor regression in residual renal functions or analysis revealed CMV constellation R-/D+ (p<0.0001) and D+serostatus (p=0.0001) to be histopathological parameters directly. However, similar Scr and CCr levels between Groups significantly associated with CMV infection. 1 and 3 may imply that HOI protects residual renal functions in 5/6 nephrectomized rats that In this cohort the add on therapy with MMF seems to be associated with a higher incidence may not be reflected to the histopathological changes in such a limited period. of CMV diseases. It has to be discussed whether this may be acceptable with projected graft survival. Pediatr Nephrol (2006) 21:1493–1635 1523

COD. PP 5 COD. PP 6 Association of the -173 G/C polymorphism of macrophage migration The protective role of resveratrol against experimentally induced inhibitory factor with susceptibility and response to glucocorticoids in pyelonephritis nephrotic syndrome H Tugtepe, N Biyikli , A Velioglu-Ogunc, S Cetinel, N Gedik, B C Yegen, G Sener H Marina Vivarelli1, Leila D’Urbano2, Gilda Stringini1, Antonia Legato1,2, Gianmarco Tugtepe (Marmara University Medical Faculty, Department of Pediatric Surgery) N Biyikli Ghiggeri3, Gianluca Caridi3, Fabrizio De Benedetti2, Francesco Emma1 Division of (Marmara University Medical Faculty, Department of Pediatric Nephrology) A Velioglu- Nephrology and Dialysis1 and Laboratory of Rheumatology2, Bambino Gesù Children’s Ogunc (Marmara University Vocational School of Health Related Professions) S Cetinel Hospital and Research Institute, Rome, and Department of Pediatric Nephrology, G. Gaslini (Marmara University Medical Faculty, Department of Histology and Embryology) N Gedik Institute3, Genoa - Italy (Kasimpasa Military Hospital, Division of Biochemistry) B C Yegen(Marmara University Division of Nephrology and Dialysis, Bambino Gesù Children’s Hospital and Research Medical Faculty, Department of Physiology) G Sener (Marmara University School of Institute , Piazza S. Onofrio 4 , 00165 Rome , Italy Pharmacy, Department of Pharmacology) , Mazharbey, Evsan Sok, Aytac Ap, No:20/6, Goztepe , 34144 Istanbul , Turkey The prognosis of idiopathic nephrotic syndrome (INS) is highly influenced by responsiveness to glucocorticoid therapy. The mechanisms underlying response to steroids Aim : Resveratrol (RVT), richly found in red wine and grape, is a polyphenolic antioxidant are unclear. possessing anti-inflammatory, anticarcinogenic, and cardioprotective effects. The present The cytokine macrophage migration inhibitory factor (MIF) is a physiologic counter- study was designed to determine the possible protective effect of RVT against acute regulator of endogenous glucocorticoids, and has recently been found to play a pathogenic pyelonephritis-induced renal injury. role in kidney diseases. The MIF promoter contains a single nucleotide G/C polymorphism Materials and Methods: In order to induce pyelonephritis in Wistar rats, 0.1 ml of E. Coli (SNP) at position –173. The –173*C allele is associated with increased MIF production, species (10x10 colonies/ml) was injected directly into the renal parenchyma, while saline with disease susceptibility and with poor response to glucocorticoid therapy in juvenile was injected as control. Pyelonephritic rats were treated with either saline or RVT (30 idiopathic arthritis. mg/kg) intraperitoneally. Twenty-hour hours or one week after E. Coli injection, rats were We have investigated the association of the MIF –173G/C SNP with disease susceptibility, decapitated and trunk blood samples were collected for BUN, creatinine, TNF-a and lactate glucocorticoid response and evolution to ESRD in 257 patients with INS and compared the dehydrogenase (LDH) determination. Kidney samples were examined both histologically allele frequencies to 355 healthy controls. and biochemically, measuring myeloperoxidase (MPO) activity, malondialdehyde (MDA) The MIF –173*C allele was significantly more frequent in INS patients compared to and glutathione (GSH) levels. controls (OR=1.67, p=0.006). When patients were divided according to their Results : E. Coli treatment, compared to control group, presented significant increases in histopathology, the MIF –173*C was more frequent in focal segmental glomerulosclerosis renal MDA level and MPO activity accompanied with increases in serum TNF-alpha and, patients (OR=1.86, p=0.01), but not in patients with minimal-change disease or in non- LDH, BUN and creatinine levels, while renal GSH level was depleted. On the other hand, biopsied patients. No association was found with the risk of progression to ESRD, at RVT treatment ameliorated pyelonepritis-induced histopathological alterations and reversed variance with a report by Berdeli. The MIF -173*C allele however, was strongly associated all the biochemical indices. with steroid resistance in FSGS patients (OR=2.61, p=0.0005). On the contrary, no Conclusion : Based on the present results, it may be concluded that RVT, which can be a association was found with response to CyclosporinA in 124 patients. natural component of daily diet, has a protective effect against pyelonephritis-induced Altogether, our results suggest that the MIF –173*C allele may confer susceptibility to INS oxidant injury and renal dysfunction. and identify steroid non-responders; targeting MIF may therefore be a useful strategy in treating INS patients with steroid resistance.

COD. PP 7 COD. PP 8 EFFECTS OF MYCOPHENOLATE MOFETILAND RAPAMYCINE Matrix metalloproteinase II expression in experimental chronic ON PERITONEAL FIBROSIS OF EXPERIMENTAL PERITONEAL pyelonephritis DIALYSIS MODEL H Alpay, N Biyikli, F Cakalagaoglu, H Tugtepe, A Ilki H Alpay (Marmara University H Dursun1, A Noyan1, S Erdogan2, M Soran1, M Buyukcelik1, M B Simsek1, A K Medical Faculty, Department of Pediatric Nephrology) N Biyikli (Marmara University Bayazit1, G Attila3, G Seydaoglu4, G Gonlusen2, A Anarat1 Departments of 1Pediatric Medical Faculty, Department of Pediatric Nephrology) F Cakalagaoglu (Marmara Nephrology, 2Pathology, 3Biochemistry and 4Biostatistics, Çukurova University School of University Medical Faculty, Department of Pathology) H Tugtepe(Marmara University Medicine, Adana, TURKEY Medical Faculty, Department of Pediatric Surgery) A Ilki(Marmara University Medical Cukurova University School of Medicine , Department of Pediatric Nephrology , 01330 Faculty, Department of Microbiology) Adana , Turkey , Moda, Yeni Fikir Sok, No :12-14/7, Fatma Erkoc A p, Kad›koy , 81300 Istanbul , Turkey

The aim of this study was to investigate the effect of mycophenolate mofetil (MMF) and Matrix metalloproteinase 2 (MMP-2) is specific mainly for collagen IV and is found to play rapamycine (RAP) on peritoneal function and morphology in a rat model of experimental an important role during inflammation in parenchymal organs. It has been suggested that peritoneal dialysis. Seventy-five male Wistar-Albino rats were divided into five groups. increased production or activity of MMPs is associated with higher tissue degradation and Rats in groups I, II, III, and IV received 15 ml 3.86% dextrose PD solution, and group V replacement by collagen. The aim of our study is to investigate the role of MMP-2 in received 15 ml normal saline daily by single intraperitoneal injection. Rats in the group I experimental chronic pyelonephritis. Seven Wistar rats were injected 0.1 ml solution daily received orally both MMF and RAP; rats in groups II and III only received MMF or containing E.coli ATCC 25922 1010 cfu/ml into left renal medullae. Five rats were RAP respectively. After 8 weeks, a 1-hour peritoneal equilibration test was performed with designed as sham group and were given 0.9 % NaCl. Pyelonephritic rats were sacrificed at 20 ml 2.27% dextrose PD solution. Net ultrafiltration was significantly found higher in 7th day after E.coli injection. Sham group rats were killed after 7 days. Renal tissues were groups I and II than group IV (p<0.05). When compared with group IV a significantly studied histopathologically by Hematoxylin and Eosine and scored for the diagnosis of decrease was detected in the number of peritoneal vessels in group I, in the number of pyelonephritis. The MMP-2 expression was studied semiquantatively by mesothelial cells in group II, and in the number of inflammatory and fibroblast cells in immunohistochemical staining by MMP-2 (Neomarker Ab-7). Chronic pyelonephritic groups I and II (p<0.05). In group I and II peritoneal membrane thickness was decreased histopathological changes were shown in the experimental group. MMP-2 expression more than group IV (p<0.05). Serum transforming growth factor-â1 level was lower in showed a statistically significant increment in the pyelonephritic group (2.7 ± 0.5) in respect group II than group IV (p<0.05). Dialysate vascular endothelial growth factor level was to sham group (1.2 ± 0.4) (p: 0.000). We conclude that increase in renal MMP-2 expression significantly decrease in group I than group IV (p<0.05). Dialysate transforming growth shown in experimental chronic pyelonephtitis is one of the responsible factors for the factor-â1 level was found significantly decreased in groups I, II and III than group IV fibrotic changes of persistent renal damage. (p<0.05). These findings show that peritoneal functions and peritoneal morphology were well preserved in MMF treated groups. We conclude that MMF may protect the peritoneal membrane from the effects of hypertonic glucose solution. 1524 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 9 COD. PP 10 The effect of oxytocin in experimental renal ischemia/reperfusion injury Severe iatrogenic hypokalemia and alkalosis in intensive care unit, case H Tugtepe, N Biyikli, G Sener, M Yuksel, S Cetinel, N Gedik, B C Yegen H Tugtepe report and etiological hypothesis (Marmara University Medical Faculty, Department of Pediatric Surgery) N Biyikli Afanetti M1, Chami L1, Casagrande F1, Tsimaratos M2, Deschennes G3, Berard E1. 1 – (Marmara University Medical Faculty, Department of Pediatric Nephrology) G Sener Service de Pédiatrie, CHU Nice (France) ; 2 – Service de Pédiatrie, CHU Marseille (Marmara University School of Pharmacy, Department of Pharmacology) M Yuksel (France) ; 3 – Service de Pédiatrie, Hôpital Trousseau, Paris (France). Presenting Author : (Marmara University Vocational School of Health Related Professions) S Cetinel(Marmara AFANETTI M University Medical Faculty, Department of Histology and Embryology) N Gedik , 2 rue spitalieri palais graziella , 06000 Nice , France (Kasimpasa Military Hospital, Division of Biochemistry) B C Yegen(Marmara University Medical Faculty, Department of Physiology) Iatrogenic hypokalemic alkalosis is classically described but poorly understood. , Mazharbey, Evsan Sok, Aytac Ap, No:20/6, Goztepe , 34144 Istanbul , Turkey Five days after allogenic bone marrow transplantation for myeloid acute leukaemia relapse; Romain, 10 years old, without any pre-existing renal pathology, presented with sepsis and Aim : Oxytocin was previously shown to have anti-inflammatory effects in different acute respiratory distress due to pulmonary aspergillosis. Among other medications, he inflammation models. The major objective of the present study is to evaluate the potential received frusemide (2,5mg/kg/d) and fosfomycin, with normal blood ionogram and protective role of oxytocin (OT) in protecting the kidney from the ischemia/reperfusion bicarbonates level. Two days later, during the hours following introduction o f (I/R) injury. gammahydroxybutyrate (gammaOH) for optimal mechanic ventilation, we observed a Materials and methods: Wistar albino rats were unilaterally nephrectomized, and subjected severe hypokalemic alkalosis (pH: 7.78, HCO3:30 mmol/l, K: 1.8 mmol/l) with to 45 min of renal pedicle occlusion followed by 6 h of reperfusion. OT (100 ìg/kg/day) or hypophosphoremia (0.13 mmol/l). Despite decreased dosage of frusemide (1mg/kg/d) and vehicle was administered twice, 15 min prior to ischemia and immediately before the important intake of KCl (8 mEq/kg/d) and phosphorus (0.4 mmol/kg/d), hypokalemia, reperfusion period. At the end of the reperfusion period, rats were killed by decapitation. alkalosis and hypophosphoremia persisted until the stop of gammaOH. Bicarbonates return Kidney samples were taken for histological examination or determination of to normal after 7 days. malondialdehyde (MDA), an end product of lipid peroxidation; glutathione (GSH), a key The use of different drugs, well known for their kalemic depletive effects is responsible of a antioxidant; and myeloperoxidase (MPO) activity, an index of tissue neutrophil infiltration. latent hypokalemia, appearing only with the use of gammaOH. Creatinine and urea concentrations in blood were measured for the evaluation of renal Metabolic alkalosis, secondary to hypokalemia, could be explained by activation of function, while TNF-alpha and lactate dehydrogenase (LDH) levels were determined to inductible H/K ATPases located in collecting duct á intercalated cells, as previously evaluate generalized tissue damage. Formation of reactive oxygen species in hepatic tissue described in animal models. Our observation clearly shows that, in humans, this induction samples was monitored by chemiluminescence (CL) technique using luminol and lucigenin can be observed in a few hours but returns to basic state in a much longer time. probes. Many questions remain unanswered, particularly the role of intracellular potassium level, Results : The results revealed that I/R injury increased urea, creatinine, TNF-a and LDH which is supposed to increase under gammaOH treatment and the aetiology of the levels in blood and MDA, MPO and free radicals levels in the renal tissue, while decreasing hypophosphoremia, Romain remaining exempt of tubular pathologies after this episode. renal GSH level. OT treatment reversed all these biochemical indices as well as histopathological alterations induced by I/R injury. Conclusions : Since OT administration improved renal function and microscopic damage, along with the alleviation of oxidant tissue responses, it appears that oxytocin protects reanl tissue against I/R-induced oxidative damage.

COD. PP 11 COD. PP 12 Multiple cytoskeletal events are critical for intracellular signals that Reactive Oxygen Species (ROS) and NF-kB Pathway Mediate High mediate transforming growth factor (TGF)-beta-stimulated fibrogenesis Glucose- Induced Pax-2 Gene Expression in Mouse Embryonic HW Schnaper, EE Sparks, SC Hubchak, S Jandeska, JF Curley and T Hayashida Mesenchymal Epithelial Cells and Kidney Explants Northwestern University , Pediatrics W-140; 303 E. Chicago Ave. , 60611-3008 Chicago , S L Zhang *, Y W Chen*, F Liu*, S Tran*, Y H Zhu*, M-J Hébert*, J R Ingelfinger* IL USA *Centre hospitalier de l`Université de Montréal (CHUM)-Hôtel-Dieu, 3850 rue Saint- Urbain, Montréal, Québec H2W 1T7, Canada; **Harvard Medical School, Massachusetts TGF-beta/Smad signal transduction is a major effector of renal fibrogenesis. We previously General Hospital, Pediatric Nephrology Unit, 55 Fruit Street, BHX-411, Boston, MA reported that classical growth factor signaling through ERK MAP kinase modulates TGF- 02114-3117, USA beta/Smad-mediated collagen expression. Further, TGF-beta1-treated mesangial cells show Centre Hospitalier de l`Université de Montréal (CHUM)-Hôtel-Dieu Hôpital , 3850 rue St- rapid (<15 min) stress fiber intensification and focal adhesion (FA) rearrangement. Urbain , H2W 1T7 Montreal , Quebec Canada Subsequent collagen expression is prevented by nonspecific blockade of Rho-family GTPases that propagate cytoskeletal signals. To relate these observations, we studied the Diabetic mellitus confers a major risk for congenital malformations, and is associated with effects of Rho-GTPase and FA kinase (FAK) activities in mesangial cell fibrogenesis. diabetic embryopathy, affecting multiple organs including the kidney. The DNA paired Specifically inhibiting RhoA activity prevents actin stress fiber formation without blocking box-2 (Pax-2) gene is essential in nephrogenesis. The present studies investigated whether a TGF-beta1-stimulated collagen I promoter activation or mRNA expression. Conversely, high glucose milieu, as might occur during diabetic pregnancy, could alter Pax-2 gene inhibiting Rac1 does not affect stress fibers but does decrease collagen induction. Blocking expression and aimed to delineate its underlying mechanism(s) of action using both in vitro RhoA, but not Rac1, also inhibits expression of smooth-muscle alpha-actin, a marker of (mouse metanephric mesenchyme (MK4) cell) and ex vivo (kidney explant from Hoxb7- epithelial-mesenchymal transition. Thus, collagen induction is independent of stress fiber GFP mice) approaches. MK4 cells were cultured in monolayer. Pax-2 gene expression was formation, and different Rho-family GTPases play different roles in the fibrogenic program. determined by RT-PCR, Western blotting, and immunofluorescent staining. A fusion gene Cells were cultured on poly-L-lysine, which prevents integrin engagement and consequent containing the full-length of the 5’-flanking of the human Pax-2 promoter linked to a cytoskeletal rearrangement. FAs were smaller on poly-L-lysine than on gelatin, and showed luciferase reporter gene, pGL-2/hPax-2 was transfected into MK4 cells with or without less adhesion-dependent FAK phosphorylation at tyrosine 397 (Y397). Transfection of FA K dominant negative IêBá (DN IêBá) plasmid (pcDNA3.1/DN IkBa) cotransfection. The mutated at Y397 decreased both ERK activity and TGF-beta1-stimulated collagen level of fusion gene expression was determined by cellular luciferase activity. Reactive expression; co-transfecting a constitutively active MEK construct that activates ERK oxygen species (ROS) generation was measured by lucigenin assay. Embryonic kidneys restored responses. Thus, cell adhesion activates FAK, ultimately leading to ERK activity from Hoxb7-GFP mice, which specifically express green fluorescent protein (GFP) in the that is essential for the collagen response. Together, these results demonstrate the UB, driven by the Hoxb7 promoter, were cultured ex vivo for the present studies. High D importance of structural and biochemical events related to the cytoskeleton in fibrogenesis. (+) glucose (25 mM), compared to normal glucose (5 mM), specifically induced Pax-2 gene Since tension on the cell activates FAK, hypertension could accelerate renal fibrosis by expression in MK4 cells and kidney explants. High glucose-induced Pax-2 gene expression enhancing fibrogenic signals. is mediated, at least in part, via ROS generation and activation of the NF-kB signaling pathway, but not via PKC, p38 mitogen activated protein kinase (MAPK) and p44/42 MAPK signaling. Pediatr Nephrol (2006) 21:1493–1635 1525

COD. PP 13 COD. PP 14 Concordance between the indirect radionuclide cystography and the Role of mitotic, pro-apoptotic and anti-apoptotic factors in human voiding cystourethrography kidney development F Cachat, P Balice, E Girardin, A Boubake r D Carev, D Krniã, M Saraga, D Sapunar, M Saraga-Babic Pediatric Department, Pediatric Nephrology Unit , Rue du Bugnon , 1011 Lausanne , Vau d Medical School Split , PAK, Histology, Medical School Split , 21000 Split , Croatia Switzerland The expression pattern of mitotic Ki-67 and anti-apoptotic bcl-2 proteins, as well as Aim of the study apoptotic caspase-3 and p53 proteins, were investigated in the human mesonephros and To study the concordance between indirect radionuclide cystography (IRC) and metanephros of 5–9 week-old human conceptuses. Apoptotic cells were additionally conventional voiding cystourethrography (VCUG) detected using the terminal deoxynucleotidyl transferase (TdT) nick-end labelling (TUNEL) method. Between the 5th and 7th developmental weeks Ki-67, caspase-3 and Methods TUNELpositive cells characterized all mesonephric structures, indicating importance of cell We compared the results of IRC performed after I123-hippuran renography and VCUG in proliferation in the growth of the mesonephros and role of apoptosis in nephrogenesis. From 91 children (182 renal units) aged 0-9 years, with respect to the presence or absence of the 7th week on, p53 and bcl-2 positive cells appeared in the mesonephros as well. vesicoureteric reflux (VUR). Concordance of the results was using Fisher’s exact test Regressive changes in the mesonephros could be regulated by activation of p53, while bcl-2 could contribute to selective survival of some tubules giving rise to adult structures. In the Results early human metanephros (5–7 weeks), Ki-67 positive cells characterized all metanephric We found a poor concordance for the presence or absence of VUR between IRC and structures, indicating a role of cell proliferation in branching of the ureteric bud and in VCUG. VUR was seen or excluded on both exam (concordance) in 115 units (63%). If we nephron formation. During the same period bcl-2, caspase-3 and TUNEL-positive cells consider VCUG as the gold standard, IRC diagnosed VUR whereas VCUG did not in 59 were found only in the metanephric mesenchyme and nephrons. Bcl-2 protein probably units (24 patients) (false positive rate 38%). IRC did not detect VUR in 8 units whereas protected nephrons from apoptosis, while caspase-3 protein controlled cell death in the VCUG did (9 patients) (false negative rate 29%). The negative predictive value of IRC was mesenchyme. At later stages (7–9-weeks), appearance of p53-expressing cells could 70%. Overall, IRC was more sensitive (92%) but less specific (24%) than VCUG. If we participate in further morphogenesis of the metanephric collecting system. The factors considered IRC as the gold standard, sensitivity and specificity of VCUG was 61% and investigated had a spatially and temporally restricted pattern of appearance in developing 70%, respectively. Expected agreement between both exams was only 23% (kappa 0.0319) kidneys. Changes in that pattern might lead to serious disturbances of kidney formation and when we compared the grading of VUR on both exams (mild, moderate and severe IRC function in early childhood. grading corresponding to grade I-II, III and IV-V, respectively

Conclusions We found a poor agreement between IRC and VCUG for the detection of VUR. IRC was more sensitive than VCUG but its clinical significance and impact on patient management remains to be defined

COD. PP 15 COD. PP 16 Insulin resistant podocytes have increased expression of the suppressor Gene expression profiling by microarray technology in urinary tract of cytokine signalling protein, SOCS7. malformations associated renal dysplasia R Lennon, V Woods, V MCCulloch, PW Mathieson, MA Saleem, RJ Coward. Academic L Artifoni(1), S Centi(1), S Campanaro(2), L Colluto(2), S Negrisolo(1), M Della Vella(1), Renal Unit, University of Bristol, Bristol, UK. W Rigamonti(3), A Capizzi(3), F Anglani(4), G Zacchello(5), L Murer(1-5). (1)Laboratory Academic Renal Unit, Lifeline Centre , Southmead Hospital , BS16 1AE Bristol , UK of Pediatric Nephrology, Department of Pediatrics, Univ.of Padua (2)CRIBI Biotechnology Centre and Dept. of Biology, Univ. of Padua (3)Department of Urology, Section of Wild type (WT) podocytes are uniquely insulin sensitive and double their glucose uptake in Pediatric Urology, Univ.of Padua (4)Department of Medical and Surgical Sciences, response to insulin. By contrast nephrin deficient Fin Major (FM) podocytes are Laboratory of Molecular Biology, Univ. of Padua (5)Nephrology, Dialysis and Transplant unresponsive to insulin. Recently, the SOCS7 (suppressor of cytokine signalling 7) protein Unit, Department of Pediatrics, Univ. of Padua. has been found to inhibit cellular insulin sensitivity by suppressing the insulin receptor Department of Pediatrics - University of Padua , Via Giustiniani 3 , 35128 Padua , Italy substrate 1 (IRS1) as demonstrated by a murine SOCS7 knockout model. Hypothesis: SOCS7 is associated with insulin responsiveness in human podocytes. Urinary tract malformations may associate to different degrees of renal dysplasia due to the Methods: Human conditionally immortalised WT and FM podocytes were cultured until dysregulation of the nephrogenetic program. fully differentiated and examined for SOCS7 and IRS1 using immunofluorescence and Gene expression studies by microarray analysis have been performed on murine models, but Western blot. SOCS7 expression was also determined in FM cells genetically rescued with to our knowledge there are no data regarding the dysplastic kidney in humans, except for nephrin (FMN). Finally SOCS7 siRNA was transfected into WT and FM podocytes and one report on multicystic kidney. We used the microarray technology with a set of 21329 insulin sensitivity was assessed by a radiolabelled glucose uptake. oligonucleotides to study gene expression profile of 8 primary cell cultures, obtained from Results: SOCS 7 is expressed in WT podocytes but has increased expression in FM congenital obstructive-uropathy-associated dysplastic kidneys. Histological analysis showed podocytes. The expression is down regulated in FMN cells with a corresponding increase in renal dysplasia in 4 cases and a normally differentiated tissue, without significant insulin sensitivity. Furthermore, WT cells had higher total IRS1 levels compared to FM histological lesions in the other 4. cells. SOCS7 immunofluoresence demonstrated diffuse cytoplasmic staining. Treatment of Statistical analysis using SAM and Z-score programs revealed a significantly different SOCS7 siRNA in WT and FM podocytes resulted in 50% reduction in protein expression expression for 449 genes (61 overexpressed and 388 underexpressed) between the and altered the insulin sensitivity of the cells. dysplastic kidneys and the normally differentiated ones, considered as controls. Conclusion: Nephrin deficient, insulin resistant podocytes have increased expression of By a careful analysis of these results, we selected 47 genes (8 overexpressed and 39 SOCS7 and reduced expression of IRS1. Transfection of nephrin reduces SOCS7 underexpressed) encoding renal structural proteins, transcriptional factors expressed during expression towards levels observed in WT podocytes. This suggests that a nephrin- SOCS7 renal differentiation and proteins involved in the turnover of the extracellular matrix. If interaction may regulate insulin sensitivity in podocytes which could be potentially confirmed on renal tissue by real time PCR, these results could be the starting point for the manipulated for therapeutic benefit. study of the signals involved in metabolic processes that produce nephrourogenesis alterations in humans. 1526 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 17 COD. PP 18 Lipoperoxide levels in children with chronic renal insufficiency Schwartz formula has to be adapted to the method of creatinine M Navarro, R Lama, A Morais, A Alonso, C Fernández, R Codoceo determination Hospital Universitario La Paz , Paseo de la Castellana 261 , 28046 Madrid , Madrid Spain L Dubourg (1, 2),P Cochat (2),G Baverel(1), A Hadj-Aïssa(1) (1)Exploration fonctionnelle rénale (2)Département de Néphrologie Pédiatrique Hôpital E Herriot, Lyon, France Atherogenesis is an important factor in progressive renal function deterioration. The aim of Presenting author: L Dubourg this study is to determinate lipoperoxide blood levels in children with chronic renal Exploration fonctionnelle renale - pavillon P , Hopital edouard Herriot , 69800 Lyon , insufficiency (CRI) and relationship among lipoperoxide blood levels, diet and degree of France renal insufficiency. Material: 65 patients (53 boys, 12 girls): group A1 (N= 35) CRI children in conservative Estimated GFR (eGFR) by the Schwartz formula (SF), which is based on plasma creatinine treatment with GFR: 20 - 70 ml/min/1,73m2 ; group A2 (N= 11) CRI children in concentration (Pcr), height (H) and a coefficient k, is the most widely formula used in conservative treatment with GFR < 20 ml/min/1,73m2; group B (N= 19) children receiving children. However, recent studies have shown a very-high inter-assay variation between the peritoneal dialysis (PD). automated methods of measurement of Pcr, which prevents the use of a uniform formula. Methods: Blood levels of malonildialdehyde lipoperoxide (MDA), lipoproteins and The aim of our study was to determine a new coefficient k adapted to our Pcr assessment vitamins A and E were determinated. A seven- day food diary, Chromo –EDTA estimated method. GFR and mean weekly kT/V (to evaluate PD effectivity) were also evaluated. Results: Mean MDA was above normal (> 7,5µmol/ml) in all three groups: A1: 334 children (152 F) aged of 11.5 ± 0.2 years [3.4 – 19.1] were referred for inulin clearance 22±3.67µmol/ml, A2: 18.09±5.83µmol/ml; B: 25.23±5.2µmol/ml. 26 children had normal (GFR). Pcr was measured by the Compensate Jaffe method (Roche, H917). Half of the MDA levels (< 7.5µmol/ml) and 39 had high MDA levels (> 7.5µmol/ml) Caloric and patients were randomly assigned to the determination of k = GFRxPcr/H and the remaining protein intake was significantly higher (p <0.05) in children with high blood MDA levels patients to the validation. while monounsaturated fatty acid intake was significantly (p <0.05) lower. kT/V was higher (p <0.05) in PD children with MDA > 7.5µmol/ml. In children < 13 years and girls > 13 years, (n=127) k = 33. For boys > 13 years (n= 40) k= Conclusions: Lipoperoxide blood levels are higher in children with CRI, whatever the 37. In the remaining children (n=167), eGFR calculated with the SF (k= 49 or 62) or by the degree of renal affectation. The amount and quality of food consumption influences adapted SF (k=33 or 37) showed a very strong correlation with GFR (r= 0.88 and 0.89 lipoperoxidation. The more effective the PD, the higher the lipoperoxidation. The best way respectively). However GFR was largely overestimated by the SF (eGFR-GFR = 50.0 ± 1.9 to increase non-protein calorie in CRI children would be adding monounsaturated fatty acid ml/min/1.73 m2 [+8.5 to +155.8]) compared to adapted SF (eGFR-GFR =1.5 ± 1,1 to their diet ml/min/1.73 m2 [-42.4 to +54.3]). - Estimation of GFR by an adapted Schwartz formula is reliable and can be used in clinical practice. When the compensate Jaffe method is used, the coefficient k must be change into 33 and 37,6 according to sex and age.

COD. PP 19 COD. PP 20 Sequential assessment of Cystatine C: can it better predict the changes Estimation of AUC for monitoring of cyclosporine in pediatric patients in glomerular filtration rate than plasma creatinine? LK van Rossum 1 (presenting author) K Cransberg 2 RAA Mathot 1 AG Vulto 1 1 Hospital L Dubourg (1, 2), P Cochat (2), G Baverel (1), A Hadj-Aïssa (1) (1) Exploration Pharmacy, Erasmus MC, Rotterdam, The Netherlands 2 Pediatric Nephrology, Erasmus Fonctionnelle Rénale et Métabolique (2) Département de Néphrologie Pédiatrique Hôpital MC-Sophia Children`s Hospital, Rotterdam, The Netherlands E Herriot, Lyon, France Presenting author : L Dubourg Erasmus MC - Hospital pharmacy , dr Molewaterplein 40 , 3015 GD Rotterdam , The Exploration Fonctionnelle Rénale- Pavillon P , hôpital E Herriot , 69003 lyon , France Netherlands

The reliability of Cystatine C (Cyst) in evaluation of glomerular filtration rate (GFR) is Therapy of cyclosporine has been guided in daily practice by trough levels. However trough largely debated. However sequential assessment of Cyst has not yet been evaluated. The levels correlate not necessarily with the area under the curve (AUC). The aim of this study aim of our study was to compare the changes of Cyst and estimated GFR (eGFR) in was to develop a simple sampling model for estimating the AUC of cyclosporine in predicting variations of GFR. pediatric renal transplant recipients. Sixteen patients (age 5 – 16 years) were studied. Eleven blood samples were drawn at 0 / 64 children (33 F) aged 11.4 ± 0.4 years [3.6 – 17.3] were referred for two sequential inulin 0.17 / 0.33 / 0.5 / 0.75 / 1 / 1.5 / 2 / 2.5 / 3 and 4 h after oral administration of cyclosporine clearance with a mean delay of 1.3 ± 0.1 years [0.8 - 2.3]. Pcr was determined with the (Neoral®). A two-compartment model (MW/Pharm) was used to calculate the AUC. The Compensate Jaffe method (Roche, H917) and Cyst with particle-enhanced AUC based on 1 sampling time (C0 / C1 / C2 / C3 / C4), 2 sampling times (C0,2 / C0,3 / immunoturbidimetric assay. eGFR was calculated with an adapted Schwartz formula (where C0,4) and 5 sampling times (C0,1,2,3,4) was compared with the reference AUC. The k=33 or 37 according to sex and age). Variation of the different parameters were considered reference AUC was calculated from all 11 sampling times with noncompartmental analysis when > 10% and 3 groups were done (decrease; stable; increase). (WinNonlin). The AUC based on 5 sampling times (C0,1,2,3,4) showed an excellent correlation with the GFR increased in 22 patients (+ 23.8 ± 2.0%), was stable in 24 (-1.5± 1.2%) and decreased reference AUC (R2 = 0.99). For the combination of 2 sampling times a correlation of 0.94- in 18 patients (- 26.8 ± 3.5 %). The changes of Cyst and eGFR in the different groups is 0.95 was found. Reduction of the number of sampling times to one resulted in a correlation shown in the figure. The variation between the two successive determinations of Cyst and of 0.8 (C2 / C3) or lower (C0 / C1 / C4). eGFR predicted accurately GFR changes in only 33/64 patients for the two parameters. The trough concentration alone is less suitable for an accurate estimation of cyclosporine AUC in pediatric patients. The sampling time C2 or C3 provides a better AUC. However, Several studies have previously demonstrated that the diagnostic accuracy of Cyst in a the combination C0,2 predicts the AUC of cyclosporine even more accuratel paediatric population is not better than the commonly used parameters. This study shows that sequential measurements of Cyst were not more reliable than eGFR. Therefore we can conclude that, in children , eGFR is probably the best parameter to evaluate both GFR and its changes. Pediatr Nephrol (2006) 21:1493–1635 1527

COD. PP 21 COD. PP 22 Rituximab therapy for steroid-dependent minimal change nephrotic Nephrotoxicity induced by Chemotherapy in Iranian Children- Single syndrome Center Experiences. RD Gilbert, Southampton General Hospital, UK E Hulse, Southampton General Hospital, 1- N Hooman - Pediatric Nephrologist ( Presenting Author) 2- Kh Arjmandi- Pediatric UK SPA Ri gden, Evelina Children`s Hospital, London, UK Oncologist 3- P Vosou g - Pediatric Oncologist Iran University of Medical Sciences (IUMS) Southampton General Hospital , Child Health Department, G Level, Tremona Road , SO16 Ali Asgar Children Hospital , N201, Vahid dasgerdi St., Modares frw . , 14387 Tehran , 6YD Southampton , Hampshire UK Iran

We present a patient with steroid sensitive but high-dose steroid dependent nephrotic Aim: We evaluated tubular and glomerular function in children who underwen t syndrome who was treated with rituximab. For 9 months following therapy she had chemotherapy. undetectable CD19 cells in the peripheral circulation. She remained in remission during this period even though therapy was reduced to low-dose, alternate day prednisolone only. After Method: Between 2003 and 2005 all pediatric cancer patients were entered to study. 9 months, CD19 cells were once again detectable. Shortly after CD19 cells became According to treatment three groups were designed including I (Initial), D (during) and S detectable again she relapsed. We conclude that B-lymphocytes play a central role in the (stop). Demographic data, cumulative doses of anticancer drugs, history of antibiotics, pathogenesis of idiopathic minimal change nephrotic syndrome (MCNS) and that rituximab nephrectomy, radiotherapy, and acute renal failure were recorded. Fractional excretion o f may have a useful role in the management of steroid dependent patients. magnesium, calcium, phosphate amylase, clearance creatinine (KL/Pcr), and urine protein to creatinine were calculated. The nephrotoxicity were graded to 0 to 9. P value less than (RDG has received a travel grant from Roche Parmaceutical to attend the ESPN 2006 0.05 was considered significant. congress) Results: 233 children (140 males, 93 females) aged 10.5 years (± 5.5 SD) in average were enrolled to study. 154 out of 233 patients had lymphoproliferative malignancies and 79 cases had solid tumors. The mean of treatment was 28.65 months and the mean of discontinuation of therapy was 25 months. Table 1 shows the blood level and fractional excretion of variables in each group. The Mean fractional excretion of phosphate, calcium, clearance creatinine and nephrotoxocity were significantly different between groups (ANOVA, P < 0.05). Metabolic acidosis was seen in 125 patients. 207 had mild to severe renal nephrotoxicity. The grade of nephrotoxicity was higher in children < 5 years, with the history of nephrectomy, radiotherapy, or nephrotoxic antibiotics (Kendall –tau, P < 0.05). Renal dysfunction was higher during chemotherapy especially with platinum, epipodophylotoxin or ifosphamide (P<0.05).

Conclusion: Frequent evaluation of renal function is highly recommended in children during and after termination of chemotherapy.

Acknowldge :This study was granted by IUMS(#519)

COD. PP 23 COD. PP 24 Disturbances of a hemostasis and antithrombotic therapy in children Nephrotoxicity in Iranian Children with Wilms` Tumor. with minimal- change nephrotic syndrome (MCNS) 1. N. Hooman , Pediatric Nephrologist, Assistant Professor 2. Kh.Arjemandi , Pediatric Y V Panyutina N D Savenkova K A Pa payan Oncologist , Associate Professor 3. P.Vosough, Pediatric Oncologist , Professor Ali Asgar Saint-Petersburg State Pediatric Medical Academy , Department of Faculty Padiatric, Children Hospital , Iran University of Medical Science. st.Litovskaya, h.2 , 194100 Saint-Petersburg , Russia Ali Asgar Children Hospital , N201, Vahid da sgerdi St.,Modares Frw., , 34317 Tehran , Tehran Iran Loirat C. et al (1992), A. Sagripanti et al (1995), A. Nakabanda (1983) have revealed disturbances of hemostasis at neprotic syndrome (NS): high levels of blood clotting factors Objective: V, VIII, X; hyperfibrinogenemia; deficiency of antithrombin and have determined We studied the correlation between renal damage and chemotherapy in children with wilms` indications to antithrombotic therapy at NS. tumor. At examination of 100 patients with MCNS during the active period is revealed: proteinuria Method: (6,01+1,9g/24h), hypoalbuminemia ((18,8+2,6g/l (80 %), 12,7+1,41g/l (20 %)), From 2003 to 2005 the severity of renal toxicity in children with wilms` tumor were hyperlipidemia, hyperfibrinogenemia ((6,9+0,8g/l), at hypoalbuminemia <10g/l a level estimated according to Cancer Therapy Evaluation Program CTC 2nd version .The fibrinogen - 10,7+1,41g/l )), decrease activity of antithrombin (63,1+6,7%). Activity of nephrotoxicity were graded to mild (0-3), moderate (4-6) and severe (7-9). The cumulative protein C was determined only at 10 patients with MCNS and was significantly over of doses of drugs were calculated. P value < 0.05 was considered significant. norm (198±11%, p<0,05). The correlation between of level hypoalbuminemia and level Result: activity of antithrombin was noted. All children had 100 % steroid sensitivity. 32 (16 males and 16 females) children aged 7.54 years in average (± 5.56 SD) were entered From 20 children with MCNS (hypoalbuminemia <10 g/l and hyperfibrinogenemia to our study. The mean (SD) of glomerular filtration rate was 107.53 ml/min (± 38), urine 10,7+1,41g/l, deficiency of antithrombin) at 4 patients have arisen thrombotic protein to urine creatinin ratio was 0.37( ± 0.87 ) , serum bicarbonate was 21.86 , fractional complications: phlebothrombosis of upper limbs (2), a mesenteric thrombosis (1) bilateral excretion of amylase , phosphate , magnesium and calcium were 3.25 % (3.89% ) , 62.33% thrombosis jugular veins (1). Characteristic feature of latter case has appeared exclusively ( 258 %) , 6 % ( 20%) , 5.32% ( 18.7% ) respectively. Table 1 shows the grade o f low activity of antithrombin (6%), restored at approach of remission up to 99%. nephrotoxicity and cumulative doses of antineoplastic agents in patients. Using stepwise 100 children with MCNS received preventive antithrombotic treatment (unfractionated and linear regression analysis, we found significant direct correlation between severity of low-molecular-weight heparins) within 10-14 days, and children with thromboses received nephrotoxicity with cumulative dosages of VP16, Ifosfamide and carboplatin (P = 0.002, R long remedial therapy. = 64%). At MCNS preventive therapy of unfractionated and low-molecular-weight heparins is Conclusion: required to children at hypoalbuminemia <20g/l, hyperfibrinogenemia >6-7 g/l, decrease Mild to moderate nephrotoxicity is seen after discontinuing of chemotherapy. Therefore activity of antithrombin<80 %. close follow up of glomerular and tubular function is recommended. Acknowledge: This study was supported by Iran University of medical sciences grant No 519. 1528 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 25 COD. PP 26 Rituximab (RTX) in the Treatment of Refractory Steroid Sensitive Comparison between the pain caused by transurethral catheterization Nephrotic Syndrome (SSNS) and venipuncture in children under three years of age M J Kemper, K Möller, K Ludwig, N Rink, D E Müller-Wiefel LM Rodríguez I Ledesma R Álvarez Ramos S Lapeña C Iglesias L Regueras Pediatric Nephrology UKE , Martinistr. 52 , D-20246 Hamburg , Germany , Servicio de Pediatría. Hospital de León , 24008 León , Spain

Some patients with SSNS show a refractory course and even redevelop steroid dependency Introduction despite maintenance treatment with cyclopsorine A (CSA). Recent immunological findings Transurethral catheterization (TUC) and venipuncture (VP) are two painful techniques suggest, that not only T- but also B-cell immunity is altered in SSNS, especially in steroid- commonly used in pediatrics. This study compares the pain caused by these procedures dependency (Kemper 2003, 2004). Therefore, we hypothesised that immunological using the pain scales in children under three years of age not yet influenced by social targeting of B-cells with antibodies directed against CD20 (Rituximab; RTX) is able to perception. maintain remission in treatment refractory patients with SSNS. Three patients with severe Methods steroid-dependency and toxicity were treated with RTX (375 mg/m² BSA given 4 times). The study was carried out in 30 children (13 male/17 female) under three years old who Patient details and response are included in table 1: underwent TUC and VP. They all were given the Bell pain rating scale, which takes into account behavioral parameters and biological ones —heart rate (HR), blood pressure (BP), Following RTX treatment, the depletion of B-cells was immediate, lasting for at least 5 and O2 saturation. months. Interestingly IgG serum levels increased despite B-cell depletion. Adverse events The results were compared using the Mann-Whitney U test (independent samples), the were not noted. In summary and conclusion RTX treatment is effective maintaining Wilcoxon test (paired samples) and the Pearson chi-square test (qualitative variables). remission in complicated SSNS. Long-term follow-up and future prospective studies are Results necessary to further define the role of RTX in the treatment of this disorder . TUC and VP caused measurable pain in the same number of children (22/30). There wasn’t difference between procedures in the intensity of pain or in the distribution in pain ranges. TUC and VP caused a significant increase in HR and in BP (p < 0,05). This increase, expressed as a percentage of the initial values, was similar in the two procedures for BP, but the increase of HR was significantly higher during TUC (p = 0,005). Conclusions TUC and VP cause pain that can be measured in 75% of our patients. The Bell scale doesn’t indicate differences in the intensity of pain caused on children not influenced by the social perception of distress. However, the raise in HR is higher during the realization of a TUC, which may indicate that this procedure causes more discomfort than VP.

COD. PP 27 COD. PP 28 Clinicopathologic Study of Hemolytic Uremic Syndrome in Children INCREASED URINARY N-ACETYL-BETA-D-GLUCOSAMINIDASE M.Mehrazma, Assistant professor , Pathologist N.Hooman, Assistant professor , Pediatric ACTIVITY IN CHILDREN WITH VESICOURETERAL REFLUX Nephrologist H.Otoukesh , Associate Professor , Pediatric Nephrologist Sh.Yousefi , S. Skálová1, P.Rejtar2, Š.Kutílek3 Department of Paediatrics1 and Department of Assistant Professor , Pathologist Ali-Asghar Children Hospital, Iran University of medical Radiology2,Charles University in Prague, Medical Faculty Hradec Králové, Czech sciences, Tehran, Iran Republic Center for Clinical and Basic Research3, Pardubice,Czech Republic , N201, Ali Asgar Children Hospital , Vahid Dagerdi St. , Modares frw. , 13437 Tehran , Medical Faculty Teaching Hospital , Department of Paediatrics , 500 05 Hradec Králové , Tehran Iran Czech Republic

Objective: Aim: The aim was to measure U-NAG in children with vesicoureteral reflux (VUR) and Evaluating the correlation between histopathological findings of renal biopsy and outcome look for relationship among selected clinical parameters. of the hemolytic uremic syndrome. Methods: 22 children. (10 boys and 12 girls, mean age 2.83 ± 2.42 years) with VUR had the U-NAG/creatinine ratio measured in the spot urine. In 8 patients the VUR was unilateral, Method: grade I-IV, and in 14 patients, the VUR was bilateral, grade I-V. In patients with bilateral 28 ( 20 males – 8 females) cases of HUS with mean age of 6 years ( ± 4.6) admitted from reflux the highest grade of VUR was taken into consideration. 1994 to 2004 . Light microscopic findings of glomeruli (sclerosis, necrosis, capillary loop Results: The U-NAG/Cr values were significantly higher in the VUR patients in thickening, crescent,…), arterioles ( hyperplastic thickening, thrombi, necrosis,…), arterial comparison to the reference data (p= 0.0001). There was no difference in U-NAG/Cr (thrombi, necrosis, intimal lipid,…), interstitial (inflammation, fibrosis, edema), medullary between children with unilateral (n=8) and bilateral (n=14) VUR (p= 0.66). There was no vessels and tubules are scored without knowledge of clinical history. Short outcome defined difference in U-NAG/Cr between patients with VUR grade I-III and VUR grade IV-V as appearing of initial improvement signs in less than 3 weeks and long outcome as (p=0.67). The U-NAG/Cr activity was high in patients with reflux nephropathy (RN; n=9) recovery or establishment of chronic renal failure and need to dialysis. P < 0.05 was when compared to reference data (p= 0.0001), however there was no difference in considered significant. comparison to children without RN (p= 0.84). Conclusions: U-NAG/Cr is increased in children with VUR grade I-V and there is a very Results : weak relationship with the grade of VUR. U-NAG/Cr is a useful marker of renal tubular The presenting symptoms were hypertension ( 64.3%) , vomiting ( 86%), fever(53.8%), impairment, however there is poor relationship with the degree of kidney damage in patients diarrhea (46.4%), abdominal pain (50%) and oliguria (46.4%). At the day of admission the with VUR . patients had pyuria(38.5), hematuria(75.5%), leukocytosis(55%), anemia(96.2%), thrombocytopenia(88.6), hyponatremia(60.8%), elevated ESR(76%) and high serum urea,creatinine and LDH (100%). Table 1 shows the pathological scoring of patients. Arteriolar lesion (arthrothrombosis ) and arterial thickening ( arterial medial thickening) had significant correlation with the serum creatinin level at time of discharge , the length of oliguria ( P =0.02 ) in short outcome , and hypertension ( P=0.01 ) or chronic renal failure (, P = 0.0001) in long term .

Conclusion : Vascular lesions (especially arteriolar ) are the most important predictor of short and long term outcome of children with HUS. Pediatr Nephrol (2006) 21:1493–1635 1529

COD. PP 29 COD. PP 30 INTRACARDIAC THROMBUS - A RARE COMPLICATION OF Conorenal syndrome, report of a case STEROID RESISTANT NEPHROTIC SYNDROME M Sharifian, M Mohkam, R Dalirani S.Skálová1, A.Lukeš1, H.Vaníèek1, T.Klein2 ,J.Hak1, P.D ìdek1, E.Oèenášková1, Shahid Beheshti University of Medical Sciences , Mofid Children Hospital, Shariati Ave, , Department of Paediatrics, Charles University in Prague, Medical Faculty Hradec Králové1, 1431943935 Tehran , Tehran Iran Kardiocentrum, University Hospital Motol, Prague, Czech Republic2 Department of Pediatrics and Nephrology Medical University of Warsaw , Marszalkowsk a 24 , 00-576 Warsaw , Poland Poland Conorenal syndrome was originally characterized during 1970 by Mainzer et al. This disease is also known as Saldino-Mainzer disease. 3.5 year old boy with first attack of steroid-resistant nephrotic syndrome was admitted to This is a rare disease characterized by cone-shaped epiphyses of the phalanges and renal hospital in May 2005. There were no mutations in the podocin gene. 8 weeks after the onset manifestations. It may result in kidney failure by the mid teen years. In 50% of the cases of disease, sinus tachycardia occurred (140 beats/min). Echocardiography revealed primary there is an associated degenerative retinal disease like Retinitis Pigmentosa and in about thrombus (size 20x11mm) in the right ventricle, reaching right ventricular outflow tract. 25% of the cases Cerebellar Ataxia is found. Patient was transferred to Kardiocentrum of University Hospital Motol in Prague. At that Cone-shaped epiphyses may occur in the phalanges as either a congenital or acquired time the thrombus has been already detected in the pulmonary artery bifurcation. Therefore, abnormality. When congenital they may be seen as a normal variant and can be either single thrombolysis with two doses of tissue plasminogen activator was initiated. After the first or multiple, they may also be associated with a multitude of skeletal dysplasias including dose the thrombus was not detectable. Lung perfusion scan revealed large multisegmental achondroplasia, Beckwith Wiedemann syndrome and multiple epiphyseal dysplasia. perfusion defect of the left lung. Haematologic parameters : thrombocytes 474 x 109/L, Acquired causes associated with abnormal epiphyseal vascular supply include dactylitis, fibrinogen 12.05 g/l (n.2-4 g/l), antithrombin III 28% (n.80-120%), protein C 213% (n.70 - e.g. sickle cell disease, thermal injury or osteomyelitis. 140%), protein S 100% (n.65 - 140% ), INR index 0.97, APTT index 1.4, S-homocystein Herein we report an eight years old girl with a collection of signs and symptoms compatible 12.5 umol/l (n.9.2-15.0 umol/l), Mutational analysis of factors V, II and MFTHR genes with Conorenal syndrome. were negative. Repeated echocardiography revealed normal cardiac function and She first presented with progressive generalized edema, dactylitis, dysuria, frequency and morphology. The patient received prophylactic doses of fraxiparin for 3.5 months followed discolored urine; on physical examination she had internal deviation of fingers of both afterwards by warfarin. Conclusion: Thromboembolism as result of hypercoagulative state hands and feet with cone shape epiphyses of middle phalanges on radiographs. Fundoscopy is a severe complication of nephrotic syndrome, however this may go unnoticed and showed mild degeneration of retina; Urinalysis revealed proteinuria (4+). Renal biopsy on asymptomatic or with a subclinical course. The intracardiac localisation of thrombus is immunoflorescence study showed IgG deposition in the mesangium and light and electron extremely rare. microscopy revealed membranous glomerulonephritis. This constellation of signs and symptoms although atypical, is compatible with conorenal syndrome.

COD. PP 31 COD. PP 32 Long-term renal function in preterms with and without TOLL LIKE RECEPTOR GENE POLYMORPHISMS IN nephrocalcinosis PEDIATRIC RENAL TRANSPLAN TATION PATIENTS IN JE Kist-van Holthe P van Zwieten EA Schell-Feith HM Zonderland HC Holscher R TURKISH POPULATION Wolterbeek F Walther AJ van der Hei jden F. Mutlubas= presenting author S.Mir A.Berdeli B.S.Yeniay O.Yava þcan C.Kabasakal Leids Universitair Medisch Centrum , kindergeneeskunde Postbus2300 , 2300 RC Leiden , Ege University Faculty of Medicine Pediatric Nephrology Department , Ege University The Netherlands Faculty of Medicine Pediatric Nephrology Department Bornova , 35100 Izmir , Turkey

The aim of the study was to examine long-term effects of nephrocalcinosis (NC) in Polymorphism in Toll Like Receptor(TLR) is reported to be associated with blunted prematurely born children. Preterm neonates (gestational age < 32 weeks) with (n = 42) and immune response to different groups of microbial pathogens.TLR gene polymorphism is without (n = 32) NC were prospectively studied at a mean age of 7.5 (± 1.0) years. Blood known to cause impaired intracellulary signalling pathway and following impaired adaptive pressure, glomerular and tubular function were measured and renal ultrasound was immune response. We investigated distribution of TLR genepolymorphism in pediatric performed. renaltransplantation patients and to reveal relationship with renal allograft nephropathy. Blood pressure did not differ in ex-preterms with and without NC, but was significantly higher than expected for healthy children, although only a minority (3 (7%) NC+ and 2 We assesed TLR gene in 69 recipients (25 living-44cadaveric) and 25 living donors. (6%) NC-) had bloodpressure > P95th percentile. Mean estimated glomerular filtration rate Patients were in 6-24 years old and followed for 58±32 months. 115 controls were included. did not differ significantly in children with (108 ± 22 ml/min/1.73m2) and without (111 ± 17 ml/min/1.73m2) NC. However, compared to healthy children more children had Polymorphisms were analyzed from genomic DNA by the PCR-RFLP based method. (moderate) chronic renal failure (glomerular filtration rate < 85 ml/min/1.73m2) in ex- Nineteen recipients were identified as chronic allograft nephropaty(CAN) with biopsy. preterms with NC than expected (6/40, p < 0.0001), in contrast to ex-preterms without NC Patients had selected for biopsy according to serum creatinine,proteinuria,blood (2/32, p NS). NC persisted long-term in 4/42 (10%) children, but was no related to renal pressure,cholesterol, CsA or TAC levels. Biopsies were evaluated according to Banff- function. TRP and plasma bicarbonate were significantly lower in children with compared criteria.CAN defined as interstitial fibrosis and tubular atrophy. to without NC, median 89 (range 69-100)% versus 92 (77-100)% (p < 0.05) and median 23 (20-28) mmol/l versus 24 (21-32) mmol/l (p < 0.01) respectively. Early morning urine Neither patients-donors nor controls were homozygote genotype for both D299G and osmolality did not differ between both groups. T399Ipolymorphisms. The comparision of heterozygote genotype patients with wild type In conclusion, nephrocalcinosis in preterm neonates can have long-term sequelae for patients there was no significant relation between both phenotypes(Table1). glomerular and tubular function, while prematurity per se is associated with high blood While there was no significant relation for D299G polymorphism with CAN(+) and CAN(-) pressure. (p>0.05), T399Imutation was significantly associated in CAN(-) recipients(p<0.05)(Table 1). TLR2 wild type Gly allele frequency was found 8 folds higher than controls in recipients. However Gly allele frequency was similar between CAN(+) and CAN(-) patients (Table2).There was significantly association between TLR4 geneT399Ipolymorphism and CAN. T399Ipolymorphism may be thought as a protective factor for CAN. TLR2 which was found significantly higher in recipients may be associated with aggressive adaptive immun response as a beginning of inflammation goes to subacute rejection. 1530 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 33 COD. PP 34 RELATIONSHIP OF CYCLOSPORINE A BLOOD LEVELS TO Bilateral giant renal angiomyolipoma in a patient with Tuberous RENAL FUNCTIONS IN NEPHROTIC SYNDROME Sclerosis A Soylu, B Kasap, Z Türky›lmaz, M Türkmen, S Kavukçu H J Hong,(presenting & corresponding author) Y H Sun, K H Cho, E Ryoo, H Tchah. , CamliCay Mah. 5182 Sk. No:112/A Urla , 35315 Izmir , Turkey department of Pediatrics, Gil medical center, Gachon medical school , department of Pediatrics, Gachon Medical School,1198 Guwerl-Dong, Namdong-gu, Incheon,Korea , 405- We aimed to evaluate the relation of blood cyclosporine A (CsA) levels to renal functions 760 Incheon , South Korea and proteinuria in nephrotic children. Tuberculosis sclerosis complex is characterised by seizures, mental retardation, cutaneous Eleven nephrotic children were evaluated retrospectively for clinical diagnoses, renal lesions and visceral harmatoma. Renal involvement begins at infancy, and the most functions, proteinuria, CsA dose and blood CsA levels. Relation of CsA levels to clinical common lesion is angiomyolipoma. We present 1 case of giant bilateral renal response, serum creatinine and proteinuria were analyzed. aggiomyolipoma in a patient with a tuberous sclerosis. A female patient, 10 years old, who had beared tuberous sclerosis was admitted to our Mean age of the children (7 boys) was 59±64 months. Clinical diagnoses were frequently hospital due to severe abdominal pain. She had experienced convulsive crises since she was relapsing (4), SDNS (4) and SRNS (3). Mean treatment duration was 20±16 months and a infant. Physical examination had revealed bilateral massive abdominal masses with mean CsA dose was 3.9±1.5 mg/kg/day. Mean C0 and C2 levels were 74±56 and 484±303 tenderness. Computed tomography had confirmed the presence of bilateral giant abdominal ng/mL, respectively. Serum creatinine was normal in all patients (0.65±0.17 mg/dL). Serum renal masses with the typical appearance of angiomyolipoma. albumin was 2.7±1.1 at the onset and 3.9±1.0 g/dL during the treatment. All patients After arterial embolisation, both radical nephrectomy was performed. The pathological achieved complete (9) or partial (2) remission and only one patient continued to have diagnosis was angiomyolipoma. The patient has been started on hemodialysis, and renal nephrotic proteinuria. There were four relapses in two patients when CsA was stopped and transplantation is planned. four relapses in two patients during CsA treatment. Blood CsA levels were 15, 39, 59 and 65 ng/mL in these relapses. Only C0 was correlated to serum creatinine (r=0.466, p=0.0001). When C0 level was grouped ase 50 or >50 ng/mL, serum creatinine was higher in the later group (0.56±0.10 vs 0.68±0.13, p=0.002). Proteinuria and serum albumin were similar among these groups.

In conclusion, C0 levels < 50 ng/mL are sufficient to achieve complete or partial remission in SDNS and SRNS. However, since breaktrhough relapses developed with C0 levels around 50 ng/mL, we recommend that C0 levels should be kept above 50 ng/mL.

COD. PP 35 COD. PP 36 PEDIATRIC DIALYTIC PATIENT AS AN ARCHETYPE OF THE INFLUENCE OF HEIGHT AND BODY MASS INDEX ON CHRONICALLY ILL CHILD: MEDICAL, ETHICAL AND SOCIAL LEFT RENAL VENOUS FLOW VELOCITY IN CHILDREN WITH PROBLEMS HEMATURIA T Jarmoliñski, B Jachimiak, D Runowski JI Shin, JM Park, JS Lee, MJ Kim Department of Pediatrics, Yeoncheon County Hospital, Dept. of Nephrology and Dialysis, District Children`s Hospital , Úw. Wojciecha 7 , 70-410 Kyunggi, Korea Department of Pediatrics, Diagnostic Radiology, and the Institute of Szczecin , Poland Kidney Disease, Yonsei University College of Medicine, Seoul, Korea Yeoncheon County Hospital , Department of Pediatrics, Jeon Gok-Eup, Eundae-Ri, 577- The aim of the study was to present medical, ethical and social problems in 35 patients (pts) 36 , 486-902 Yeoncheon-Goon , Kyunggi-Do South Korea treated with renal replacement therapy (RRT) at our centre between 2000 and 2006. Epidemiological data, patients’ psychical state, qualification to transplantation, social and Background: To determine the influence of anthropometric parameters on left renal venous economic conditions of the families and outcome were analysed. The main medical flow velocity in children with hematuria. problems were: difficulties with qualification to transplantation in 16 pts, psychical Methods: During the past 3 years, we performed a renal Doppler ultrasound in 216 children disturbances in 18, lack of vascular access in 3 and numerous severe complications of long- with macro- (n=40) or microhematuria (n=176). Peak velocity (PV) was measured in the lasting RRT in 1. Ethical dilemmas were referred to: RRT in mentally disabled children transverse plane at two points in the left renal vein (LRV), one at the hilar portion of the with myelomeningocele and insufficient family supervision, continuing RRT in terminally LRV, and the other at the aortomesenteric portion. Anthropometric measurement of height, ill children, the choice of proper mode of RRT for children with limited socio-economic weight, body surface area (BSA), and body mass index (BMI) were made at the time of conditions and demands of family to stop RRT. Only 8 families were „normal”. ultrasound. Unemployment was proved in 25 families, in 16 cases the child was looked after by at last Results: They were divided into two groups according to the PV ratios of the LRV: one parent, in 14 families there were no enough money even to buy all medicines, at 7 nutcracker group (PV ratio > 4.0, n=72) and non-nutcracker group (PV ratio < 4.0, n=144). homes the person who drunk too much lived together with the child, in 5 – close relative There were no differences in the mean age, gender, the incidence of gross hematuria and was mentally disabled and in 3 – criminal. Parents of 18 pts didn’t collaborate with doctors flank pain between the two groups. There were no differences between the two groups in or even harm the child. Despite all these problems 20 pts were successfully transplanted. regard to weight and BSA. However, height was significantly higher in nutcracker group Six children died (4 with no chances for transplantation). Conclussion: chronic renal failure than non-nutcracker group (p=0.031), and BMI was significantly lower in nutcracker group in children is a disease of a body, soul and social environment, which face doctors, the than in non-nutcracker group (p=0.006). Furthermore, the PV ratios of the LRV in 216 family and social support system with numerous medical, ethical and organising challenges. children with hematuria inversely correlated with BMI (PV ratio = 6.936 – 0.17 X BMI, r = -0.188, p=0.006). Conclusions: These results suggest that patients with nutcracker syndrome were leaner than those without nutcracker syndrome, and height and BMI may influence on left renal venous flow velocity in patients with hematuria. Pediatr Nephrol (2006) 21:1493–1635 1531

COD. PP 37 COD. PP 38 THE CLINICAL SIGNIFICANCE AND EVALUATION OF GROSS CYCLOSPORINE A (CyA) VERSUS MP PULSES (MP) IN THE OR MICROSCOPIC HEMATURIA IN CHILDREN TREATMENT OF SEVERE HENOCH-SCHÖNLEIN NEPHRITIS JI Shin, JM Park, JS Lee, MJ Kim Department of Pediatrics, Yeoncheon County Hospital, (HSN) Kyunggi, Korea Department of Pediatrics, Diagnostic Radiology, and the Institute of J Ronkainen 1), M Ala-Houhala 2), M Antikainen 3), T Jahnukainen 4), O Koskimies 3), J Kidney Disease, Yonsei Universit y College of Medicine, Seoul, Korea Merenmies 3), T Örmälä 6), Juha Turtinen 1), Matti Nuutinen 1) 1)Department of Pediatrics Yeoncheon County Hospital , Department of Pediatrics, Jeon Gok-Eup, Eundae-Ri, 577- and Adolescence, Oulu University Hospital 2)Department of Pediatrics, Tampere 36 , 486-902 Yeoncheon-Goon , Kyunggi-Do South Korea University Hospital 3)Hospital of Children and Adolescents, University of Helsinki 4) Department of Pediatrics, Turku University Hospital 6)Department of Pediatrics, Hospital Background: The aim of this study was to determine the role of the laboratory and of Hyvinkää radiologic evaluation of hematuria in children, and to evaluate the prevalence of nutcracker , Department of Pediatrics and Adolescence, Oulu University Hospital, PO Box 23 , 90029 syndrome in children with unexpalined hematuria. Oulu , Finland Methods: We retrospectively evaluated 216 children presented with gross (n=40) o r microscopic hematuria (n=176) from the years 2002 to 2004. The diagnostic studies Efficacy of CyA and MP treatment was evaluated in a prospective study consisting 19 included a personal and family history, complete blood cell count, electrolytes, HSN-patients (6 girls, 13 boys; mean age 9.2 years) with nephrotic range proteinuria or biochemistry, coagulation profile, serology for hepatitis B, ANA, ASO titer, complemen t ISKDC-grade III – VI. Ten patients received CyA (5 mg/kg) for 1 year and 9 patients MP- C3 and C4, urine culture, urinary calcium/creatinine, 2-D ultrasonography and excretory pulses (30 mg/kg i.v. x 3) with additional prednisone (30 mg/m2 p.o.) for 4 months. Both urography. groups received ACE-inhibitor (2.5 – 15 mg/day). Mean follow-up time was 2.9 years (1.1 Results: Complete blood count, electrolytes, biochemistry, and the coagulation profile were – 5.6). normal in all patients. Positive ANA was detected in 13 patients, but repeat testing and anti- At start the treatment groups did not differ, and the mean proteinuria was 161 mg/m2/h (13 ds DNA showed no evidence of autoimmune diseases. Serum C3 concentrations were low – 510). Remission was defined as U-protein/U-creatinine ratio <200 or dU-protein < 40 in 4 patients. Hypercalciuria was found in 26 patients (12%). Ninety five percent of the 2-D mg/m2/h. ultrasonography and 97% of the excretory urography showed no abnormal findings. A Ten CyA patients (100%) compared with 5 (56%) MP patients achieved remission within 3 positive family history of hematuria was reported in 11% of patients. Nutcracker syndrome months (÷2 test p=0.03). At latest control 10 patients (7 CyA, 3 MP) had no renal was present in 60 of the 149 children (40%) in whom no other explanation for hematuria symptoms, 7 had symptoms but normal renal function (3 CyA, 4 MP) and 2 (MP) had a was ascertained. decreased GFR (23 and 62 ml/min/1.73 m2). In four (44%) MP patients an additional Conclusions: We suggest that urinary calcium/creatinine ratio and renal Doppler ultrasound immunosupressive treatment had to be started (CyA, MMF) after mean 1.6 years (0.2 – 2.7) should be included in the initial routine evaluation of children with hematuria because from the MP - pulses. All CyA patients achieved remission and they had been free from idiopathic hypercalciuria and nutcracker syndrome were found to be two most common CyA treatment for mean 1.5 years (0.2 – 3.7) at the end of follow-up. At latest control mean causes of hematuria during childhood. U-protein and mean S-creatinine were 310 mg/l and 51 ìmol/l in CyA group and 846 mg/l and 78 ìmol/l in MP group, respectively.

CyA seems to be more effective than MP in treatment of severe HSN.

COD. PP 39 COD. PP 40 What is the best method for quantification of nephrotic range Levamisole in steroid-sensitive nephrotic syndrome (SSNS): an proteinuria in children? international multicenter double-blind randomized trial: the last news. J Dusek, K Vondrak, M Hladikova, T Seeman, E Simkova, J Kreisinger, P Dvorak, J Janda, MP Gruppen*, MP Merkus,** JC Davin* *Paediatric Nephrology and **Centre for J Vavrinec Paediatric Clinical Epidemiology, Emma Children’s Hospital/Academic Medical Centre, Pediatric Dept. Univ. Hospital Motol , V Uvalu 84 , 150 06 Prague 5 , Czech Republic Amsterdam, The Netherlands. Emma Children`s Hospital/AMC , EKZ/AMC; Pediatric nephrology department, Proteinuria is the most important prognostic indicator in kidney diseases. The estimation of Meibergdreef 9 , 1105 AZ Amsterdam Z-O , North Holland The Netherlands 24h proteinuria is often incorrect particularly in children. Only spot urine is required fo r calculation of urinary protein/creatinine and protein/osmolality ratios. The confirmation of a favourable effect of levamisole to prevent relapses of SSNS in an The aim of our study was to find out the most reliable test for quantification of nephrotic adequately powered, double blind, placebo-controlled, randomized, multi-centre clinical range proteinuria in children. trial will promote consensus on its therapeutic place in childhood. Such a trial has been The urinary protein excretion was examined in 24h specimens. Altogether 565 urine designed and funded by the Dutch Kidney Foundation. One hundred patients have to be samples in 106 pts with proteinuria 40-2318mg/m2/h (median 106) have been evaluated. In enrolled to allow subgroup analyses for different grades of steroid dependency. Patient with the same urine specimen we determined creatinine (UCr), protein concentration (UP) and no relapse during the first year of follow-up will pursue the study for one more year to osmolality (UOsm) for calculation of protein excretion, UP/UCr and UP/UOsm ratios. evaluate long term efficacy and side effects. The demonstration of a beneficial effect of the Urine samples of children with urine output <1ml/kg/h and glycosuria were excluded. drug will allow its official registration in this indication. Up was measured by the quantitative turbidimetric method, UCr by enzymatic (mmol/l) and The study will be performed in collaboration with ACE Pharmaceuticals, a Dutch company, UOsm by freezing point depression method. The standard evaluation of 24h proteinuria which is willing to commercialized levamisole again. The request of ACE to EMEA that (mg/24h and mg/m2/h) was correlated with UP/UCr and UP/UOsm ratios. The statistical levamisole should obtain the denomination of orphan drug has been accepted in August significance of correlation coefficient differences was tested by SISA software. 2005. EMEA has positively reacted on the study protocol (February 2006). However, Results: The best correlation was found between proteinuria in mg/m2/h and UP/UOsm bridging experiments have to be done to show that ACE levamisole tablets (5,10, 25 and 50 ratio (r=0.85). The correlation between proteinuria (mg/m2/h) and UP/UCr ratio was less mg) should have the same solubility proprieties as Ergamisol (past Jansen-Cilag significant (r=0.84). The difference between these two correlations (0.85 vs. 0.84) was not Levamisole) for which a pre-clinical dossier is already approved. This will delay the start of significant (p=0.2). patients enrolment to October 2006. Interest to participate might be signalled to Dr MP Conclusion: UP/UOSM ratio and UP/UCr are equal for estimation of nephrotic range Gruppen (study coordinator:[email protected]) or to JC Davin (principal investigator: proteinuria in children. However examination of UOsm is cheaper than UCr (in our [email protected]) conditions 2.5 fold cheaper).

The nephrotic range proteinuria >40mg/m2/h corresponds with UP/UOsm ratio >2.6 and UP/UCr ratio >185. 1532 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 41 COD. PP 42 Solitary kidney volume ultrasound biometry among patients with Percutaneous renal biopsy in children: revisiting 30 years of experience agenesia and after nephrectomy aged 3-6, 7-11, 12-17 years H G Pinto 1 Presenting author R Sousa 1 C Afonso 1 S Sampaio 2 C Valbuena 2 H Jardim MD Saed Alkhatib, MD O V Levicheva, MD, I V Nahodkina, MD, phD, prof. N D 1 1 Departamento de Pediatria, Hospital de S. João, Porto 2 Serviço de Anatomia Savenkova Patológica, Hospital de S. João, Porto saint-petersburg state pediatric medical academy , Lytovskaya St 2 194100 Saint- , Hospital de S. João- Departamento de Pediatria Alameda Prof Hernani Monteiro , 4200- Petersburg, Russia , 194100 Saint-Petersburg , Russia Russia 319 Porto Porto , Portugal

Objective: the main purpose of the investigation was in the volume comparison of solitary In the last decades, pediatric percutaneous renal biopsy has progressively increased due to kidney due to agenesia (52) and nephrectomy caused by hydronephrosis (55) in patients technical improvements and clinical benefit from diagnosis/prognosis establishment and aged 3-6, 7-11 and 12-17 years old with the volume of one of two kidneys in practically therapeutical options. healthy children (75). The authors revised the percutaneous renal biopsies performed in their paediatric Methods: the size and the volume of kidneys were estimated by ultrasound biometry. department from April 1977 to February 2006, in order to evaluate both epidemiological Length of kidney – the greatest size received by longitudinal scanning, width – least and clinical features of the cases and procedure’s safety. transversal, thickness – least forward – back size received by transversal scanning at the One hundred ninety seven biopsies from native kidneys were performed in 186 patients, level of hiluses renalis. with a male preponderance of 1.2:1. Children’s age spanned from under 3 months to 18 The formula of the truncated ellipse was used to account the volume of the solitary kidney. years old, with a median of 8.6 years. The most common indications for biopsy were Volume of the kidney (sm3) = length x width x thickness (sm3) x 0.53. hematuria (48%); nephrotic syndrome (35%); nephritic syndrome (5.6%); acute renal Results: in 52 patients with solitary kidney due to agenesia the volume of kidney was failure (3.5%) and chronic renal failure (2.0%). Biopsies were performed under sedation 77.1±9.4 sm3 (3-6 years old), 118.6±16.3 sm3 (7-11 years old), 191.5±11.6 sm3 (12-17 and kidneys identified by fluoroscopy till 1984, and afterwards by ultrasound examination. years old). Adequate renal tissue was obtained in 93.9% of cases. The complication rate was 4%: gross In 55 patients with solitary kidney due to nephrectomy caused by hydronephrosis the hematuria occurred in 6 cases and perirenal haematoma in 2 cases. The most frequent volume of kidney was 103.1±12.1 sm3 (3-6 years old), 126.9±10.2 sm3 (7-11 years old), diagnosis were: minimal-change disease (16.8%); IgA nephropathy (14.2%); Henoch- 189.3±12.4 sm3 (12-17 years old). Schoenlein purpura (8.6%); focal sclerosis (8.1%); membranoproliferative In 75 practically health children the volume of right kidney was 43.0±2.6 sm3 (3-6 years glomerulonephritis (8.1%); idiopathic (benign familial) hematuria (6.6%); systemic lupus old), 70.2±6.6 sm3 (7-12 years old), 98.9±6.0 sm3 (12-17 years old). erythematosus (6.0%); Alport syndrome (3.6%); acute poststreptococcal glomerulonephritis Conclusion: the larger volume of the solitary kidney due to agenesia and nephroctomy in (3.6%); membranous glomerulopathy (2.2%); hemolytic-uremic syndrome (1.5%); children 3-17 years old is the result of the compensatory renal hypertrophy. hypertensive nephropathy (1.5%); acute tubular necrosis (1.5%); congenital nephrotic The range of compensatory renal hypertrophy of the solitary kidney caused by agenesia in syndrome (1.0%); other (16.2%). children aged 3-6, 7-11, 12-17 years old was 179.49%, 169.89%, 193,67% agreeably. Due We conclude that percutaneous renal biopsy is a safe procedure, with a considerable to nephrectomy caused by hydronephrosis was 239,99%, 180,7%, 191,67% agreeably importance in distinguishing clinical entities which have identical symptoms and different comparing with the volume of kidney in groups of practically healthy children. prognosis and treatment responsiveness.

COD. PP 43 COD. PP 44 Pharmacokinetics and therapeutic efficacy of cyclosporine in children The prevalence of nephropathies and uropathies in children and with frequently relapsing idiopathic nephrotic syndrome teenagers in Russia Masashi Morooka, Satoru Kisohara, Kayoko Umemura, Yasuto Yamamoto, Nihoko Ito, Natalya Perepyolkina, Albina Vyalkova, Igor Zorin Yoshizo Asano , Matrosskij pereulok, 22, kv.4 , 460000 Orenburg , Russia Fujita Health University School of Medicine , Department of Pediatrics, , 4701192 Toyoake , Aichi Japan We studied dynamics of prevalence of nephro- and uropathies in children and teenagers in Russia for the period 1997-2001 years by the official statistic data, which were presented in Background: Cyclosporine (CsA) has been used in frequently relapsing (FR) idiopathic report "Health of the population of Russia and activity of public health departments", which nephrotic syndrome (NS). But the relationship between the concentration and the efficacy in was made by Department of statistics and computer science of Ministry of public health of children with NS is still unclear. We studied the relationship between pharmacokinetics Russian Federation. (PK) and therapeutic efficacy of CsA. We established that there was a negative tendency in growth of prevalence of nephro- and Material and methods: Sixteen patients (mean age 9.6, M:F 9:7) with steroid dependent and uropathies in children and teenagers in Russia. Nephro- and uropathies increased on 9,3 %î FRNS were entered into this study. They all took microemulsion formulation of CsA in children and teenagers in Russia for last five years, especially in teenagers. The (2.3~5.9mg/kg/day) devised twice a day before the meal. We assayed concentrations of prevalence of nephro- and uropathies in children and teenagers increased on 16,3 %î for the CsA and estimated the PK parameters using concentration time profiles by moment period from 1997-2001 years. analysis. We devised these patients into two groups with estimated Cmax over than Glomerulopathies, tubulopathies prevailed in the structure of nephropathies (more than 42 600ng/ml (group A) or less than 500ng/ml (group B), and compared the number of %) in children. The same diseases in teenagers were about 30 %. But uropathies were in relapsing and the amount of prednisolone (PSL) between before and after starting CsA in 2,3-3,5 times more in teenagers, than in children. There was no increase of patients with each groups. CRF for last 5 years in Russia. But prevalence of CRF was higher in teenagers, than in Results: The mean values of estimated Cmax were as follows, group A(n=8); 882.2 ng/ml, children. There was no increase of patients with urolithiasis from 1997 till 2001 years in group B(n=8); 298.8 ng/ml. Only group A showed statistically significant reductions in both Russia. the number of relapse (pre; 2.4/year, post; 0.6/year) and the amount of PSL (pre; 0.66mg/kg/day, post; 0.22mg/kg/day). Group B also showed these reductions, but they were not statistically significant. Discussion and Conclusion: From our data, higher Cmax of CsA showed better therapeutic effectiveness in children with FRNS, so we should set Cmax over than 600ng/ml. Furthermore, we need to conduct further investigations because of small sample size and add the analysis of side effects such as tubular interstitial damages due to high concentration of CsA. Pediatr Nephrol (2006) 21:1493–1635 1533

COD. PP 45 COD. PP 46 Diagnosis of urolithiasis in children Interleukin-18 in serum and urine of children with idiopathic nephrotic V Pichault, J F Sabot, M Jouvenet, I Canterino, J Harambat, A Liutkus, X Martin, H Dodat, syndrome L Dubourg, P Cochat Département de pédiatrie, Hôpital Edouard- Herriot & Université K Kiliú-Pstrusiñska, D Zwoliñska, A Medyñska, A Wawro Claude-Bernard, Lyon, France , Dpt. of Pediatric Nephrology, Wrocùaw Medical University , 50-369 Wrocùaw , Poland , Hôpital Edouard-Herriot & Université Claude-Bernard, Département de pédiatrie et INSERM U499 , 69437 (CEDEX 03 LYON , France Interleukin-18 (IL-18) is one of immunoregulatory cytokines that could be involved in the pathogenesis of idiopathic nephrotic syndrome (INS) in children. It is a product of activated Background : It is an important issue to define the cause of urinary calculi disease in macrophages, induces INF-gamma and TNF alpha in T-cells and NK, and IL-8 in children in order to prevent recurrence and possible impairment of renal function. The eosinophils, stimulates the proliferation of activated T cells and regulates of Th1 cytokines etiological approach comes from both biological and clinical arguments. including IL-2, GM-CSF and INF-alpha. Patients and methods : This is a retrospective study over a 11 year-period in one pediatric The aim was to evaluate IL-18 concentrations in serum and urine of children with INS and center including only children who underwent physical renal stone analysis (including both determine the possible role of this cytokine in the course of disease. morphological microscopy examination and infrared spectroscopy) ; individual clinical and 67 children with INS, aged 3 to 16 years (mean 9 +/- 4) and 15 age-matched normal biological (plasma and urine) data were also collected. The aim of the study was i) to bring controls were included in the study. The patients were divided into 2 groups according to information about the prevalence of each type of urolithiasis in the population, and ii) to activity of the disease: I (n=37) -INS in relapse, II (n=30)-INS in remission. Serum and identify the role of biological investigations, clinical data and physical analysis of stones in urinary IL-18 were determined by ELISA and normalised in urine to the urinary creatinine determining the primary disease. (cr) concentration. In children with INS serum biochemical parameters, clearance of Results : A total of 84 patients were included. The sex ratio was 2.1 and the median age was endogene creatinine and 24hour proteinuria were measured. 6.4 years [range 0.5-17.9]. The main components of calculi were: carbapatite 40.5%, Urinary IL-18 concentration (213.51 +/- 162.15 pg/mg cr) was significantly higher whewellite 16.6%, weddellite 13.3%, purine 6.0%, cystine 4.7%, struvite 3.6%. Further (p<0.001) in group I compared with group II (64.74 +/- 10.95 pg/mg cr) and normal biological investigations lead to a diagnosis of urinary tract infection in 46.4%, controls (37.03 +/- 4.1pg/mg cr). Serum IL-18 concentration was significantly higher in hypercalciuria in 21.4%, hyperoxaluria in 10.7% and cystinuria in 4.7%. In 29.8% of the group I than normal controls (14.64 +/- 3.02 pg/ml and 11.3+/- 1.0 pg/ml, respectively; patients, urinary tract malformation was associated. In 22.6 % of the cases, urolithiasis was p<0.001). The differences between group II and controls were not significant. Urinary IL-18 considered as idiopathic. correlated positively with serum IL-18 (r=0.503 p<0.001) and with urinary protein excretion Conclusions : The combination of direct (physical) and indirect (biochemistry) methods (r=0.58, p<0.05), but no correlations were found with other laboratory data. leads to reliable diagnostic approach to urolithiasis in children. Such a strategy is able to Elevated serum and urinary IL-18 levels in children with relapse of nephrotic syndrome optimize specific management of the underlying disease. suggest the role of IL-18 in the pathophysiology of INS. IL-18 in serum and urine may reflect the disease activity of INS.

COD. PP 47 COD. PP 48 TUBEROUS SCLEROSIS AND POLYCYSTIC KIDNEY DISEASE IN CYSTATIN C: AN EARLIER MARKER OF RENAL FUNCTION A 2 YEAR - OLD - GIRL LOSS IN CHILDREN S Petrovic – Tepic(Presenting author), S Milanovic,S Keleman, A Serdar, J Samardzic – A Pota, ML Sirico, A Pota, A Fella, C Pecoraro Department of NephrUrology, Santobono Predojevic,V Novakovic,O Ljuboja Children`s Hospital, Naples, Italy , Clinic for Children’s Diseases, Dept. of Pediatric Nephrology, Ul. 12 beba bb, 78000 Santobono Children`s Hospital , Department of NephroUrology, via Mario Fiore n° 6 , Banjaluka, Bosnia and Herzegovina , 51000 Banja Luka , Republika Srpska Bosnia 80129 Naples , Italy Herzegovina Cystatin C (Cys-C) serum level is proposed as GFR marker. We verified Cys-C value to We present a patient with early manifestation of autosomal dominant polycystic kidney estimate GFR in 483 children (M/F 274/209; age 8.67±4.86 years). Creatinine, Body disease (ADPKD) and was found to have tuberous sclerosis (TSC). Weight and Height were evaluated. We made 1441 determinations: from 1 to 18 per patient. Tuberous sclerosis is an autosomal dominantly inherited multisistemic disease. It is We included subjects with different GFR values (CrC, Schwartz Formula) divided in five characterized by the development of hamartomas, predominantly in brain and kidneys. The groups according to primary nephropathy (1-Hypo-dysplastic, 2-heredo-familial, 3- second most frequent renal manifestation is cysts, predominantly singl cysts, but Tubulointerstitial, 4-Vascular, 5-Glomerular) and compared with controls (group 0). Linea r presentation of polycystic kidneys diseases during early childhood has been reported. Renal regression, covariated for age , gender and Body Surface Area, was calculated. GLM for cysts may be the initial manifestation of the disease and occure in about one - third of repeated measures was performed to evaluate the followup. A significant correlation patients with TSC. The TSC2 gene for tuberous sclerosis is localised on chromosome between CrC and Cys-C for each group was found (Tab.) 16p13. 3 imediately adjacent to PKD1, the gene for ADPKD. Group N M/F R p A two year–old –girl was admitted to hospital for investigation because of recurent 0 146 75/71 -0.39 0.0001 infections of urinary tract and elevated blood pressure. At the age of six months she had one 1 111 76/35 -0.87 0.0001 epileptic seizure and after that she had received anticonvulsive therapy without any new 2 60 30/30 -0.89 0.0001 atacks. 3 121 63/58 -0.75 0.0001 Abdominal ultrasonography demonastrated bilaterally enlarged kidney with multiple cysts 4 21 14/7 -0.84 0.0001 resembling those seen in ADPKD. Brain magnetic resonance showed tipical signs of TSC. 5 24 16/8 -0.88 0.0001 Renal function was still normal. There was no consanguinity between parents and the TOT 483 274/209 -0.86 0.0001 family history of renal disease or TSC were negative. The two methods were compared by multiple determinations during follow-up (up to 7 in These findings are highly suspicious of TSC2 - PKD contaguous gene syndrome wich can 36 months). 51 subjects of the group-1 with at T0 normal renal function were divided in two be confirme by genetical analysis. subgroups: GROUP A: 23pts, 18M, with at T0 CrC and Cys-C normal values (113±15 an d 0.8±0.06, respectively), kept at T36 months CrC normal values (106±7) and Cys-C increased values (0.98, p<0.05) ; GROUP B: 28 pts, 18M, with at T0 CrC normal values (108±7) and Cys-C high levels (1.08±0.17), had, at T36 months, a decrease of CrC (69±15, p<0.05) and a further increase of Cys-C serum levels (1.61±0.51, p<0.005). Our results indicate that Cys-C is equal to CrC as GFR marker. The independence of Cys-C from muscular mass is an advantage in children. The Cys-C in the group of Hypo-dysplastic nephropathies is an earlier marker of GFR loss. 1534 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 49 COD. PP 50 PREVALENCEAND RISK FACTORS FOR MALNUTRITION An Evaluation of Quality of Life of Mothers of Children with Enuresis DURING CHRONIC RENAL INSUFFICIENCY, DIALYSIS AND Nocturna RENAL TRANSPLANTATION ACCORDING TO THE A Egemen1, I Akil2, E Canda2, B Cengiz Ozyurt3, E Eser3 Ege University, School of ANTHROPOMETRY-BIOIMPEDANCE ANALYSIS NUTRITION Medicine, Department of Pediatrics1, Celal Bayar University, School of Medicine, SCORE (ABN SCORE) Departments of Pediatrics2, and Public Health3 Celal Bayar University, School of Medicine, Department of Pediatrics , Celal Bayar A Edefonti, F Paglialonga, M Picca, S Loi, G Marra, G Ardissino, MR Grassi, S Salera, D Universitesi, Tip Fakultesi, Pediatri Anabilim Dali , 45020 Manisa , Turkey Savo, L Ghio Nephrology and Dialysis Unit, Clinica Pediatrica De Marchi, Milano Universisty of Milan, Clinica Pediatrica De Marchi , Nephrology and Dialysis Unit, Via The aim of this study is to evaluate the role of enuresis nocturna on quality of life of the Commenda 9 , 20122 Milan , Italy mothers. The data were collected at the out-patient clinic of the Celal Bayar University Hospital. The prevalence and causes of protein-calorie malnutrition in children and young adults with Mothers who have a child with enuresis (n=28) and mothers who have a child with minor chronic renal insufficiency (CRF), treated conservatively, or ESRD, treated with peritoneal health problems (n=24) were selected. Groups were in balance for the background dialysis (PD), hemodialysis (HD), or renal transplantation (Tx), are poorly known. variables. We assessed the nutritional status of 262 patients, mean age 13.1 ± 6.7 years (79 CRF, 65 Short Form Health Survey (SF-36) Questionnaire, The Beck Depression Inventory (BDI) PD, 25 HD, 93 Tx) with the ABN score, an objective score system based on 9 parameters and Spielberg`s State-Trait Anxiety Inventory (STAI) were applied to all mothers. The derived from anthropometry and bioimpedance analysis. Patients’ demographic, clinical, Turkish version of SF-36 includes eight multi-item scales (physical function, role physical, dietary and laboratory data were also collected. bodily pain, general health, vitality, social functional, role emotional, and mental health). Malnutrition (ABN score < 10.33) was diagnosed in 17.1% of CRF, 43.1% of PD, 40% of All items are summed and transformed to form a scale from 0 to 100. HD and 15.1% of Tx patients. Prevalence of malnutrition was significantly higher in The quality of life pattern of the mothers who have a child with enuresis was quite similar patients < 18 years than in older patients in every group. from those mothers in control group. Only, the mothers of children with enuresis had Comparison between patients with ABN score < 10.33 and those with ABN score > 10.33 significantly lower quality of life scores in the SF-36 for the bodily pain subscales indicated as significant risk factors for malnutrition a lower chronological age (p<0.005), a (p=0.017). We observed significant difference between groups according to BDI; mean longer dialysis duration (p<0.05) and a reduced residual urine output (p<0.005) in patients score was higher in mothers who have a child with enuresis nocturna (p=0.002). There was on dialysis, a high proteinuria in CRF and Tx patients (p<0.05). Serum albumin, total no significant difference between groups according to the STAI. protein and hemoglobin strongly correlated with the ABN score in every patient group, Although we observed no significant change in quality of life of mothers who have children serum transferrin in CRF and Tx patients only. with enuresis nocturna, a significant difference according to BDI and bodily pain subscale In conclusion, malnutrition is common in patients with chronic renal failure, particularly in of SF-36 shows that the mothers were negatively affected for having a child with enuresis those on dialysis. An unexpected prevalence is found also in transplanted patients. nocturna. Identification of risk factors and an early diagnosis of malnutrition could allow for a better nutritional treatment.

COD. PP 51 COD. PP 52 MAY CYTOKINES DIFFERANTIA TE STEROID SENSITIVE AND Audit of Chlorambucil use in Paediatric Patients with Nephrotic STEROID RESISTANT NEPHROTIC SYNDROME ? Syndrome(NS) F. Mutlubas (presenthing author) S. Mir A. Berdeli B. S. Yeniay MI McCulloch, L Savage, P Gajjar, P Sinclair, D Maytham, G Van Dugteren, J Ege University Faculty of Medicine Pediatric Nephrology , Ege University Faculty of Wiggelinkhuizen Department of Paediatric Nephrology, Red Cross Children`s Hospital, Medicine Pediatric Nephrology Bornova , 35100 Izmir , Turkey University of Cape Town Red Cross Children`s Hospital , Renal Unit Ward E2 , 7700 Cape Town , South Africa Nephrotic syndrome is identified according to response to treatment as steroid sensitive (SSNS) and steroid resistant nephrotic syndrome SRNS). Either SSNS or SRNS are Introduction considered immune-mediated diseases as T cell diseases. Cytokines of T-helper1 (Th1) and Children with complicated nephrotic syndrome (NS) may require aggressive T-helper2 (Th2) are known to play different roles in different clinical types of NS. Different immunosuppressant therapy. Many agents have been used and in our experience polymorphic changes affects gene expression of cytokines. To investigate distrubition of Chlorambucil has been an effective agent. gene polymorphisms of cytokines in Th1-Th2 accesses and to clarify assosication of them Aim with different types of NS were aimed and IL1B-3953C/T, IL4-590T/C, IL2-330T/G, IL1B- To document the use of Chlorambucil 35C/T, IFNã-874T/A, IL1-RN1, IL1-RN2, IL1-RN3, IL1-RN4, IL1-RN5 polymorphisms Methods were investigated. Retrospective review of 23 patients. (mean age 6 years 9 m) with NS treated with Chlorambucil (2001-2006) including: 32 SSNS and 30 SRNS patients were included with control groups of same age and ethnic •Histological type of NS groups. All cytokin genotypes where analysed by AS-PCR method. Statistisc for allelic •Duration of NS frequencies were performed by Fischer’s Exact test. •Indication for Chlorambucil treatment •Dose and duration of therapy T allele of IL1B-3953C/T was significantly higher in SRNS group than controls although •Complications of therapy similiar within SSNS group. There were no differences in groups for IL4-590T/C, IL1B- •Remission rate and duration of remission 35C/T and IFNã-874T/A . IL2-G allele had found to be associated with both patient groups Dosage regime: Chlorambucil 0.2mg /kg orally for 8 weeks with steroids. with controls without relation in themselves(Table1). White cell count (WCC) checked 2 weekly. Results The polymorhic IL1 RN2 was extremely high in each NS groups contraversion to controls. • Diagnosis: IL1RN1 was the dominant gene in controls. There was no significant relation for NS in Minimal change NS (13), Mesangioproliferative NS (9) FSGS (1) themselves for all genotypes of IL1-ra(Table2). • Duration of NS prior to treatment: mean 2 years 9 months • Indication for treatment: Ýt is obvious that a high allele frequency of IL1RN2 in both two NS groups could point out Steroid sensitive, Frequent relapses(7), Steroid dependence(13) the susceptibility to NS. However there had been no any allele results for distinguishing NS, Steroid resistance(3) SSNS or SRNS. • Complications: Total no. of patients (10) Low WCC <4 (2), Skin infections (3), Viral myositis + skin It is obvious that a high allele frequency of IL1RN2 in both two NS groups could point out infection(1), TB + skin infection (1), Diarrhoea (1),Peritonitis(1) the susceptibility to NS. However there had been no any allele results for distinguishing NS, • Remission rate: SSNS or SRNS. No remission 2 Remission for a limited period <3 months 2(poor compliance) 3-6 months 2 6-12 months 1 12-24 months 3 Ongoing remission 11 (range 5 months-4.5 years) Current treatment 1 Lost to follow-up 1 Conclusion Chlorambucil is an effective agent in maintaining remission in NS. Our incidence of serious side-effects was low, despite many patients coming from an impoverished background with a high incidence of TB. Skin infections were a common complication. Pediatr Nephrol (2006) 21:1493–1635 1535

COD. PP 53 COD. PP 54 INTERFERON GAMMA LEVELS IN PATIENTS WITH FAMILIAL Intravenous Pulsed vs Oral Cyclophophamide Therapy in Steroid MEDITERRANEAN FEVER Dependant Nephrotic Syndrome E Baskin1*, , S Ozen2 , N Besbas2 , R Topaloglu2, A Bakkaloglu2 Depts of Pediatric 1. AS Abeyagunawardena 2. RS Trompeter 1.Department of Paediatrics, University of Nephrology and Rheumathology , Baskent1 and Hacettepe University2 , Ankara, TURKEY Peradeniya, Sri Lanka 2.Nephrology Unit, Great Ormond Street Children’s Hospital, Baskent University hospital , Dept of Ped Nephrology 6.cadde 72/3 , 06490 Ankara , London, UK Turkey , 155, George E de Silva Mawatha , A155 Kandy , Sri Lanka

Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by Childhood nephrotic syndrome is characterised by a relapsing course resulting in significant recurrent episodes of fever, polyserositis, and arthritis. Endogenous interferon(IFN)-gamma corticosteroid burden, or prescription of cytotoxic immunosupressive therapy. There is no is a Th1 type proinflammatory cytokine that plays a key regulatory role in the immune consensus regarding the dosage and route of administration of cyclophosphamide (CYC) in response. IFN-gamma also directly and rapidly induced MEFV expression in neutrophils, steroid-dependant nephrotic syndrome (SDNS). This randomised controlled study carried monocytes and fibroblast. We aimed to evaluate the levels of endogenous interferon-gamma out between 2002 and 2005 at a single centre in Sri Lanka to compare the outcome between in patients with familial Mediterranean fever (FMF). children with SDNS treated with intravenous or oral CYC. We studied 61 patients with FMF (32 asymptomatic, 17 during an attack, and 11 with amyloidosis) and 12 age matched controls. IFN-gamma levels were also compared among Thirty six sequential children with SDNS with evidence of steroid toxicity were randomly colchicine treated and untreated groups. Commercially ELISA kits were used in the allocated to receive either oral or intravenous CYC. Fifteen via intravenous route (500 measurement of IFN- gamma levels. mg/m2 monthly for 6 months - total dosage 132mg/kg), and 21 via the oral route (3 mg/kg Median plasma IFN-gamma levels in patients with acute attack were significantly higher per day for 8 weeks - total dosage 168mg/kg). Both groups received an identical tapering than asymptomatic FMF patients and age matched controls (P < 0.05). FMF patients with regimen of oral prednisolone for 6 months. Full blood counts were performed weekly secondary amyloidosis had also significantly higher IFN-gamma levels than asypmptomatic during oral therapy and monthly during intra venous therapy. The progress of these children patients and controls (p<0.05). was assessed regularly for one year. IFN- gamma may contribute to the inflammatory cascade of FMF. Increasing of this cytokine during acute FMF attacks may be considered as compensatory responses. In the oral CYC group, 2 patients developed bone marrow suppression, 3 had serious infections and 11 had significant alopecia. These side effects were not observed in the intravenous group. At one year of follow up there were no significant difference in the relapse rate in the 2 groups ( oral - 9/21 vs intravenous - 6/15. p >0.05 comparison of 2 proportions using Standard Error).

In SDNS, intravenous CYC therapy has the same efficacy of oral CYC in inducing sustained remission with fewer side effects and lower total dosage.

COD. PP 55 COD. PP 56 The early and late response of pneumococcal vaccination in nephrotic Two cases of cystinuria with prenatal brigth colon. A prenatal feature o f children cystinuria. H Alpay, N Biyikli, T Akkoc, I Gokce, N Ozdemir, N Yildiz F Broux1, D Eurin2, B Hecketsweiller3, V Brossard4, G Landthaler1 1 Unité de , Moda Yenifikir sokak, No: 12-14/7, Fatma erkoc apt , 81300 Istanbul , Turkey Néphrologie, Département de Pédiatrie Médicale, 2Service de Radiologie Pédiatrique, 3Laboratoire de Biochimie et 4Service de Pédiatrie Néonatale. Hôpital Charles Nicolle, Children with nephrotic syndrome (NS) are susceptible to serious pneumococcal disease CHU de Rouen. like peritonitis, cellulitis, pneumoniae and sepsis. Pneumococcal polysaccharide vaccine Unité de Néphrologie, Département de Pédiatrie Médicale , 1, rue de Germont , 76031 (PPV) is recommended for nephrotic children older than 2 years of age. The aim of our Rouen , France study is to assess the clinical and laboratory efficiacy and side effects of PPV in NS patients. 27 children with steroid responsive NS and 20 controls were enrolled in the study. Case 1: in a 33 years old woman G1P1, a routine ultrasound at 33 weeks, revealed A 23 valent PPV was used for vaccination. Blood samples were obtained before and 4 hyperechogenicity of whole colonic content (bright colon). No other digestive anomaly was weeks and 3 years after vaccination. ELISA test was used to quantitate serum total detected. Amniotic fluid volume, fetal morphology and MRI were normal. At 39 weeks o f antipneumococcal capsule polysaccharide immunoglobulin G antibodies. Antibody levels gestation she delivered a normal male newborn without digestive symptom. At 14 months before vaccination, 4 weeks and 3 years after vaccination were compared. The mean age of of age, he developed an acute pyelonephritis which revealed lithiasis in the right collecting the nephrotic children and controls were 7.8 ± 3.1 years and 8.6 ± 2.6 years, respectively. system . Metabolic analysis were performed and amino acid chromatography revealed Baseline antibody titers and antibody titers following 4 weeks and 3 years of vaccination for cystinuria. nephrotic children and controls were 33.3 ± 18 mg/L, 100.9 ± 22.2 mg/L, 135.5 ± 114.2 Case 2: In a 28 years old woman G2P1 at 33 weeks gestation, ultrasound examination mg/L and 32.8 ± 13 mg/L, 101.6 ± 41.1 mg/L, 144.3 ± 64 mg/L, respectively (table 1). The diagnosed bright colon as in the firth case. There was no other ultrasound abnormality. At increase in pneumococcal antibody levels in the 4th week (p: 0.000) and the persistence of 39 weeks of gestation, she delivered a normal female newborn, without digestive symptom. antibodies in the 3 year (p: 0.000) were statistically significant in respect to baseline levels Taking account of the firth case, the diagnosis of cystinuria was considered. Urinary amino and similar to the increases observed in the control group. None of the children showed side acid chromatography confirmed cystinuria. A high concentration of cystine in meconium effects after vaccination and none of the patients experienced any pneumococcal infection was also detected. during the study period. We conclude that PPV is a well tolerated and immunogenic vaccine in nephrotic children. The association of bright colon and cystinuria is not fortuitous. The pathophysiologic hypothesis is that in a foetus with cystinuria , the dibasic amino acids are excessively excreted in urine, so in the amniotic fluid, which is swallowed by the foetus. In the colon, absorption of water induces therefore concentration of dibasic amino acids which could explain the hyperechogenicity. Moreover, a defect of the intestinal absorption of dibasic amino acids in cystinuria, increases concentration of cystine in the colon. Although this association must be confirmed in a larger population, a prenatal bright colon could lead to search cystinuria. 1536 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 57 COD. PP 58 Early onset amyloidosis in two siblings with Phenotype-II FMF Chemokine receptor 2 and chemokine receptor 5 polymorphisms in K Bek1, B Can2, O Özkaya1, F Karagöz2 1 Ondokuz May›s University Faculty of nephrotic patients Medicine, Department of Pediatric Nephrology, Samsun, TURKEY 2 Ondokuz May ›s N Biyikli, H Alpay, N Bozkurt, I Gokce, N Ozdemir, T Ispir N Biyikli (Marmara University University Faculty of Medicine, Department of Pathology, Samsun, TURKEY Medical Faculty, Department of Pediatric Nephrology) H Alpay(Marmara University Ondokuz May›s University Faculty of Medicine , Pediatric Nephrology , 55139 Samsun , Medical Faculty, Department of Pediatric Nephrology) N Bozkurt (Istanbul University Turkey Medical Faculty, Department of Molecular Medicine) I Gokce (Marmara University Medical Faculty, Department of Pediatric Nephrology) N Ozdemir(Marmara University The term “Phenotype II” in Familial Mediterranean Fever (FMF) patients is defined as the Medical Faculty, Department of Pediatric Nephrology) T Ispir (Istanbul University Medical patients who present first with the clinical findings of renal amyloidosis without any Faculty, Department of Molecular Medicine) previous typical FMF attacks. Its incidence among all FMF patients is reported to range , Kozyatagi, Sinan Ercan Cad, Oztor sitesi C Blok 38/38 , 34736 Istanbul , Turkey from 7 % to 25 % in various series from Turkey. Here we present two siblings diagnosed as phenotype II FMF both at the age of 6 years with two years apart. They were two of four Chemokines have been implicated in the pathogenesis of renal diseases. Recent studies siblings in a nonconsanguinous family. There were no family history of FMF. The boy was focus on the relationship between genetic variants of CC-chemokine receptors. Genetic brought to our institution first with the complaints of edema and nephrotic range proteinuria variation in CC-chemokine receptor 2 (CCR2) and CC- chemokine receptor 5 (CCR5) at the age of 6 years. His renal biopsy revealed amyloidosis. In genetic analysis acting through inflammatory responses may affect atherosclerosis and glomerulosclerosis. homozygous M694V mutation of MEFV gene was detected. Colchicine was started. The aim of our study is to investigate whether genetic variants of CC-chemokine receptor 2 Screening of other siblings was planned and family was informed. But parents brought the (CCR2) 641 and CC- chemokine receptor 5 (CCR5) delta 32 are associated with focal sister two years later with swelling of the legs, palpebra and abdomen without any history segmental glomerulosclerosis (FSGS) and its clinical course. 25 chilren with biopsy proven of recurrent abdominal pain. She was six years old and had nephrotic syndrome. Her renal FSGS and 30 healty controls were included in the study. FSGS patients were grouped biopsy also revealed amyloidosis and MEFV gene mutation was M694V/M694V just as her according to the severity of the disease. Genotypes of the CCR2 641 and CCR5 delta 32 brother. This is the most commonly reported MEFV gene mutation from our country. were studied by polymerase chain reaction followed by digestion with appropriate Therefore its presence together with renal amyloidosis should alert the clinican for the restriction endonucleases. Distribution of GG, GA, AA genotypes of CCR2 641 in patients screening of other family members and even initiating colchicine treatment without waiting with FSGS and controls were 92% (GG), 8% (GA), 0% (AA) and 72.5% (GG), 25% (GA), the results of genetic tests. This seems even more crucial when the phenotype II patients are 2.5% (AA), respectively. There was no statistically significant difference in respect to concerned. genotype distribution. To evaluate the correlation between chemokine receptor genetic variants and the course of FSGS, we compared the distribution of the genotypes in patients with declining renal function with that in children who had preserved renal function. Patients with declining renal function displayed higher frequency of GG genotype (100%) than in patients with preserved renal function (88%). None of the patients and controls were positive for CCR5 delta 32 mutation. These results suggest that polymorphisms of CCR2 gene and CCR5 gene are not related with the development of FSGS, but genetic polymorphism of CCR2 may be associated with the clinical course of FSG

COD. PP 59 COD. PP 60 PROGNOSTIC EVALUATION OF THE MULTICYSTIC Abnormal thyroid function test in nephrotic syndrome DYSPLASTIC KIDNEY WITH CONSERVATIVE TREATMENT IN S KIm, M Sung, S Sohn PAEDIATRIC POPULATION Pusan National University, College of Medicine , Department of Pediatrics, Ami-dong, R Chimenz, G Conti, L Silipigni, R Gallizzi, C Fede Paediatric Nephrology and Dialysis Suh-ku , 602-739 Busan , South Korea Unit, University of Messina, Italy University of Messina , Paediatric Nephrology and Dialysis Unit, via Consolare Valeria , Background: Most of the studies in nephrotic syndrome showed normal TFT including FT4 98100 Messina , Italy Italy and TSH levels although total T4 and TBG levels were low. But in congenital nephrotic syndrome, a state of biochemical hypothyroidism is commonly seen and bilateral Aim of this work was to investigate the prognostic evolution of the multicystic dysplastic nephrectomy reverse hypothyroidism. So we wanted to verify the state of serum thyroid kidney (MCDK) with conservative treatment and the compensatory growth of the contra hormone levels in nephrotic syndrome(not congenital) in children. lateral kidney. Patient and method: We studied TFT in 23 nephrotic children(5.3 ± 4.4 yrs of age) in both From 1997 to 2004 (follow-up median: 42 months), we followed periodically 17 children disease state and remission state. with MCDK (age: from 12 months to 13 years; 8 boys and 9 girls). Five children (29%) had Results: associated uropathy malformations (UM). All patients underwent 6-month follow-up Nephrotic Remission P-value examinations with ultrasonography until two years-old and annual follow-up for the S.Alb(g/dL) 1.4 ± 0.6 2.5 ± 1.6 0.0006 successive years to control the possible involution of the multicystic kidney and the contra T3 (ìg/dL) 54.9 ± 30.9 128.4 ± 35.7 0.0122 lateral kidney growth [percentile measure of the longitudinal diameter (LD)]. T4 (ìg/dL) 3.2 ± 2.2 8.3 ± 2.1 0.0061 We did not see malignancy evolution. We have documented a complete involution of the FT4 (ìg/dL) 0.3 ± 0.2 1.5 ± 0.5 0.0012 multicystic kidney in 65% of the patients and partial in 23%. Twenty percentage of children TSH (ìIU/mL) 12.2 ± 14.6 3.2 ± 2.3 0.1431 MCDK with associated UM presented a complete involution, while the complete resolution TBG (ìg/mL) 8.5 ± 4.6 20.4 ± 7.3 0.0143 was in the 83% of the children without associated UM (p<0.05). The compensatory kidney hypertrophy (LD: >95°percentile) was seen in the 20% of the children MCDK without Conclusion: In childhood nephrotic syndrome there might be transient hypothyroid state associated UM (p<0.01). The blood pressure and renal function were always normal. contrary to euthyroid state so far known. More studies including metabolic rate In conclusion, our data confirm that the conservative treatment is the best management measurement are needed to confirm these transient state of hypothyroidism before use of versus surgery therapy in MCDK. The concomitant presence of associated UM decreases any therapeutic intervention in young chidren with nephtotic syndrome and transient the probability of the contra lateral kidney compensatory hypertrophy. hypothyroidism Pediatr Nephrol (2006) 21:1493–1635 1537

COD. PP 61 COD. PP 62 Iga GN in Epidermolysis Bollosa:case report SPECTRUM OF SENSITIZATION TO ALLERGENS IN CHILDREN R Calabrese , F Tammaro,L Lospalluti , G Aceto , R Penza Dip.Biomedicina Dell`Età WITH Evolutiva -Università di Bari NADEZHDA SAVENKOVA, IRINA BATRAKOVA, INGATUR Department of Biomedicine Evolutive Age- , University of Bari-P.zza G.Cesare , 70124 Department of Pediatric Nephrology, St.Petersburg Pediatric Medical Academy, BARI , ITALY Italy St.Petersburg, Russian Federation , Department of Pediatric Nephrology, St.Petersburg Pediatric Medical Academy, St.Petersburg, Russian Federation , 194100 st-petersburg , Recesssive dystrophic Epidermolilysis Bollosa (RDEB) was diagnosed at birth in a 14-year- lytovskaya str-2 Russia old male ;he presented firstly with microhematuria which subsequently evolved into intrafections macrohematuria; renal biopsiy was performed and light microscopy revealed a . diffuse increased extracellular matrix and mesangial cells and a focal segmental The spectrum of sensitization to allergens in Children with Minimal Chang Nephrotic glomerulosclerosis with severe chronic tubulointwerstitial damage. Immunofluorescence Syndrome (MCNS) was studied. showed IgA mesangium deposits. In view of the absence of active histological lesions he Among 120 patients with MCNS 100% had initial corticosteroid sensitiveness. Steroid started ACE inhibitors therapy. Five years later ,due to progressive worsening,of the renal dependence and frequent relapsing in 120 children with MCNS were associated with atopic function(serum urea 172 mg/dl , creatinine 14,2 mg/dl) he started haemodialisis by CVC 3 in 78 (65%): dermatitis and urticaria (38,5%); rhinitis (20,5%), conjunctivitis (14,1%), times a week:He is currently in therapy with albumin , erytropoietin ,calcitriol.To our bronchial astma (3,85%). knowledge, this is the first report of renal biopsy performed in a patient affected by EB. 78 patients had increasing in blood specific Ig E to allergens: alimentary allergens (88,5%), household allergens (61,5%), inhaled allergens of grasses and tress (30,8%). Among 69 patients with MCNS increased level of alimentary allergens specific IgE was detected: milk 66,7%, egg protein 49,3%, citrus 42%, hen protein 37,7%, pork meat 18,8%, beef meat 21,7%, buckwheat croup 21,7%, oat croup 13%. Among 48 patients with MCNS increased level of household allergens specific IgE was detected: home and library dust and D.farinae 85,4%, dog and cat wool 50%, sheep wool 14,6%. Among 25 MCNS patients with spectrum of sensitization to inhaled allergens of grasses and tress: 18 (75%) of them had respiratory tract allergy, 12 (48%) of them had season relapses of MCNS annually. Conclusion: our data reveal the wide spectrum of sensitization to allergens in children with MCNS. We revealed the association of frequent relapses and increased level of specific IgE in blood. There are allergen-induced variants of MCNS in children.

COD. PP 63 COD. PP 64 MCP1 and EGF in the evaluation of renale damage in children with Hemopoietic cell transplantation in children and its consequences for Hipodisplasia and VUR renal function R Calabrese, F Tammaro ,C.Franco , G.Aceto,G Francioso ,R Penza Dip.Biomedicina L Kovács, J Horáková, I Boïová, S Šufliarska, J Lukáè dell`Età Evolutiva -Universitry of Bari -Italy University Children´s Hospital , Department of Pediatrics , 83340 Bratislava , Slovak Dip.Biomedicina Età Evolutiva , Università di Bari Pzza G.Cesare , 70124 BARI , ITALY Republic Italy The aim of this study was to investigate the effect of hemopoietic cell transplantation (HCT) Reflux nephropathy and renal hypodisplasia are recognised as a major causes of end stage on renal function in children. In a 10 year period, 117 children received HCT at the Bone renal failure in children. Epidermal growth factor (EGF) produced by tubular cells plays a Marrow Transplantation Unit of the Department of Pediatrics. The study was performed pivotal role in the modulation of tubular cell growth, while Monocyte chemotactic peptide 1 retrospectively using the serial measurements of serum creatinine and estimated glomerular (MCP1) is a specific activating factor for pathogenesis of tubular damage. We have studied filtration rate. Patients characteristics (sex, age, diagnosis) conditioning regimen, type of the urinary excretion of MCP1 and EGF in 49 children: 11 with monolateral renal HCT, major complications (sepsis, veno-occlusive disease and graft-versus-host disease) hypoplasia without VUR, 15 with VUR without hypoplasia, and 8 with hypoplasia and and the use of nephrotoxic medication were listed. The mean age of the patients was 10.5 VUR, 15 patients have been enroled as case control. Aim of our study has been the years (2-19 years), the follow-up period was 2 months to 10 years (mean 23 months) Within evaluation of MCP1 and EGF as useful parameters for monitoring the progressive renal the first months after HCT, 13 (11%) patients died, 11 from transplant related complications damage.The parameters were evaluated with T-Test Student.Our data showed that urinary other than renal failure and two from relapse of the disease. Thirty five (29,8%) children excretion of EGF and MCP1 are significantly higher in reflux nephropathy and renal had a period with acute renal failure (defined as doubling of serum creatinine). Fifty percent hypodisplasia versus normal kidneys, so that we can suggest that these cytokines are of them had it during the early period, but none of them developed acute renal insufficiency involved in the pathogenesis of tubulointerstitial damage. after the initial 60 days. During the entire post-transplant follow-up period a total of 41 CONTROLL IP RVU (35%) patients died, 12 (10.2 %) from transplant related complications other than renal MCP-1u failure and 29 (24.7%) from relapse of the disease. None of the children in this retrospective (pg/ml) 247,42±222 * study developed chronic renal insufficiency or needed dialysis. It is concluded, that acute 746,95±757 ** renal insufficiency is a frequent sequela in children following HCT and likely results from 573,1±638*** drug toxicity.

EGFu (pg/ml) 51003,37±42403° 96515,93±74967°° 144224,68±141343°°°

* vs ** p=0,046 * vs *** p=0,02 ° vs °° p=0,02 ° vs °°° ns 1538 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 65 COD. PP 66 Calcification inhibitors in children with renal diseases Nephrotic Syndrome In Children With Genetic Syndrome H Ziolkowska, J Wojnar, M Pa ñczyk-Tomaszewska, M Roszkowska-Blaim Department of O V Shatochina, I M Osmanov, M S Ignatova, L S Prikhodina, V V Nestrujeva, O V Pediatrics and Nephrology Medical University of Warsaw Katysheva, T A Nikishina, O J Turpitko Department of Pediatrics and Nephrology Medical University of Warsaw , Marszalkowsk a Institute of Pediatrics & Children Surgery, Moscow; Russia , Pediatrics & Children 24 , 00-576 Warsaw , Poland Surgery, Moscow; Russia , 127412 Moscow , Taldomskaja Street, 2 Russia

The aim of the study was to estimate the serum concentrations of calcification inhibitors: The aim of this study to determine clinical features and outcome of children with genetic fetuin-A and osteoprotegerin (OPG) in children with renal diseases. syndrome and nephrotic syndrome. Fifty three children aged 13.33.9 years:18 with idiopathic nephrotic syndrome (NS) and We examined 20 children with genetic syndrome and nephrotic syndrome (mean age 35 with chronic renal failure (CRF) were examined. The control group (C) consist of 22 8,7±8,1 years). We performed renal biopsy (n=10/20) and cytogenetic study (n=15/20). healthy children, aged 10.83.3 years. The serum concentration of fetuin A, calcium (sCa), Steroid-resistant nephrotic syndrome has 18/20 children. phosphorus (sP), protein (P), albumin (A), total cholesterol (TC) and triglycerides (TG) Mean age of onset of nephrotic syndrome has age of 2,3 years (0-9 years). 15/20 patients were measured. The daily protein excretion (DPE) in children with proteinuria (mg/kg/day), have reached the endstage renal disease at the age of 9,8 years. 35 % patients have never serum parathormone (PTH) and osteocalcine (OC) in children with CRF were analyzed. hadn’t oedema. Genetic syndromes includet: Denys-Drash syndrome (n=4); Frasier Results:(table1)Fetuin A was the lowest in group NS. In this group significant correlations syndrome (n=2); Femily nephrotic syndrome autosomal-dominant (n=2); Turner syndrome were found between fetuin A and sCa (r=0.62, p=0.008), P (r=0.59, p=0.01) and A (r=0.64, (n=2); Cockayne`s syndrome (n=1); Klinefelter syndrome (n=1); Galloway-Mowat p=0.005) and negative correlations with TC (r = - 0.68, p = 0.002) and DPE (r = -0.79, p = syndrome (n=1); Galactosialidosis (n=1); Alport`s syndrome (n=2); Lowe`s syndrome 0.0001). OPG was the highest in group CRF. In these children the PTH level was 147142 (n=1); Spondyloepiphyseal dysplasia (n=1); Familial Mediterranean Fever (n=1); pg/ml and OC level was 414378 ng/ml. OPG in children CRF correlates with PTH (r=0.3, Chromosome 13q- syndrome (n=1). Renal biopsy revealed: diffuse mesangial sclerosis in 2 p<0.05) and OC (r=0.38, p<0.002). patients with Denys-Drash syndrome; focal and segmental glomerulosclerosis in 2 patients Conclusions: Low concentration of fetuin A in children with nephrotic syndrome may be with Frasier syndrome; mesangial proliferative glomerulonephritis in patient with Femily the additional agent to promote the atherogenic lesions. The elevated levels of OPG in nephrotic syndrome autosomal-dominant; hypoplastic dysplasia of kidney in 2 patients with children with ESRD may reflect the higher bone turnover in these patients. Femily nephrotic syndrome autosomal-dominant and Chromosome 13q- syndrome; amyloidosis in patient with Familial Mediterranean Fever. Patients with Alport`s syndrome had a pathology of glomerular basal membranes at a electron microscopy. Three of fou r patients with Denys-Drash syndrome and two patients with Frasier syndrome had a hermaphroditism. Cytogenetic study shown different abnormal karyotype in 9/15 children. In conclusion, the majority of children with genetic syndrome have steroid-resistant nephrotic syndrome with characterised by early age of onset and progressed to endstage renal disease.

COD. PP 67 COD. PP 68 Spectrum of renal disease in Malaria ACE inhibition can improve orthostatic proteinuria associated with G R Soleimani nutcracker syndrome pediatric department_ZDMU_Zahedan_IRAN , Ali -ebne Abitalib hospital_ T-S Ha, E-J Lee Zahedan_IRAN , ------Zahedan , Sistan & Bloochestan Iran Chungbuk National University Hospital , Department of Pediatrics , 361-240 Cheongju , Chungbuk South Korea Background: Malaria , a common health problem in certain parts of the world , has a considerable morbidity and mortality. Clinically significant renal and renal-related disorders Orthostatic or postural proteinuria is a benign condition characterized by the presence of commonly occur in infection with Plasmodium falciparum and P. malariae. Falciparum protein in urine samples collected in the upright position during the day and its absence in malaria causes fluid and electrolyte disorders, transient and mild glomerulonephritis, and the supine position. Recently, nutcracker phenomenon has been documented as the source acute renal failure (ARF). It appears that ARF is mediated by a complex interaction of of postural proteinuria. mechanical, immunologic, cytokine, humoral, acute phase response, nonspecific factors, The nutcracker phenomenon refers to compression of the left renal vein between the aorta and hemodynamic factors. Parasitized erythrocytes play a central role in all aforementioned and superior mesenteric artery, resulting in elevation of pressure in the left renal vein, pathogenic factors of ARF.Other complications of Malaria are cerebral malaria, anemia, leading to congestion of the left kidney and occasionally to collateral veins formation. hypoglycemia, pulmonary edema, hemoglubinuria, septicemia, shock, acid-base imbalance. Entrapment of the left renal vein is a cause of left-sided gross hematuria, ureteral and Method: In this study 25 cases of malaria in children between 6 months to 13 years old were peripelvic varices, unexplained left flank pain and variable degrees of orthostatic admitted in our hospital at Zahedan , IRAN and renal complications of these patients were proteinuria. studied. We report the case of a 14-year-old girl with orthostatic proteinuria, diagnosed as having Results: Of These 25 cases two cases had hemoglubinuria and one case had volume nutcracker syndrome by doppler sonography and MR angiography. Because daily protein depletion and all these three cases had malaria due to falciparum. excretion was more than 1.5 grams over 3 years of follow up, we decided to perform a renal Conclusion: Antimalarial drugs are still the cornerstone of treatment of falciparum biopsy which revealed moderate mesangial cell proliferation in all glomeruli. Her overt infection. Because of the hypercatabolic state of falciparum malaria-induced ARF, orthostatic proteinuria disappeared after a treatment of ACE inhibition. hemodialysis as well as peritoneal dialysis should be immediately performed when there is In conclusion, nutcracker syndrome remains a rare but important cause of elevated protein a rapid increase of creatinine concentration. excretion, which could induce mesangial changes and be improved by ACE inhibition. Keywords: Renal, Malaria, Hemoglubinuria Pediatr Nephrol (2006) 21:1493–1635 1539

COD. PP 69 COD. PP 70 Congenital Nephrotic Syndrome: is pre-emptive nephrectomy really COMBINED CYCLOSPORINE A AND MYCOPHENOLATE always necessary? MOFETIL THERAPY IN CHILDREN WITH NEPHROTIC IM Ratsch, R Tobaldi, F Staffolani, GV Coppa Service of Paediatric Nephrology and SYNDROME Dialysis - Dep. of Paediatrics United Hospitals Umberto I-G.M. Lancisi-G. Salesi - Ancona; J Kwinta-Rybicka, A Moczulska, I Ogarek, A Pelkowska, E Slowiaczek, Z Stec, K Politechnic University of Marche, Italy. Wilkosz, K Sancewicz-Pach, J A Pietrzyk Department of Pediatric Nephrology, University , Service of Paediatric Nephrology and Dialysis - Dep. of Paediatrics United Hospitals Pres. Children’s Hospital, Jagiellonian University, Kraków, Poland. G. Salesi - Ancona; Via Corridoni 11 , 60123 Ancona , Ital y Dpt. of Pediatric Nephrology , University Childrens` Hospital, Jagiellonian University , 30663 Kraków , Kraków Poland Congenital Nephrotic Syndrome of the Finnish-type(CNF) is a rare autosomal recessive disorder of podocytes caused by a mutation of the NPHS1 gene on Chromosom 19q13. The management of steroid-resistant (SR) and steroid-dependent (SD) nephrotic syndrome Variability of genotype and phenotype may influence genetic counselling and hence (NS) in children remains a clinical challenge for pediatric nephrologists. Prolonged treatment options offered to parents who may prefer “withdrawing from any treatment” to exposure to steroids, cyclosporine A (CsA) and alkylating agents increases the risk o f invasive management with “bilateral pre-emptive nephrectomy” and peritoneal dialysis serious side-effects. Nephrotoxicity is a well-known dose-dependent adverse effect of CsA (CCPD)until transplantation. We describe 3 preterm neonates suffering from CNF, who treatment leading to deterioration of renal function. In many patients, the reduction of CsA after complicated delivery and intensive treatment with albumin infusion during the first dose results in relapses and further intensification of treatment is needed. Mycophenolate months of life were managed only with intensive nutritional treatment (intermittent mofetil (MMF), used mainly in transplantation, was recently successfully used in NS normoproteic hypercaloric nasogastric-tube-feeding) until end-stage renal disease, CCPD patients. This study aimed to assess the safety and function of the kidney in children with and transplantation. In all cases, hypoalbuminemia (0.6-0.8 g/l) and heavy proteinuria SR and SD NS treated with CsA after introduction of MMF. The study included 9 children remained significant during the period of renal hyperfiltration, unless the use of ACE- with NS (2 girls, 7 boys) aged 7-19.5 years (a mean of 15.7) treated with CsA and steroids. inhibitors. Oral and intraperitoneal aminoacid solutions were helpful in maintaining Remission was not obtained with previous treatment regimens, and severe adverse reactions adequate growth. Psychological and neurological development was normal. Intensive with deterioration of renal function were observed. CsA was combined with MMF management with albumin infusion was necessary at least 1-2 times /year during viral administered twice daily in a dose of 180-600mg/m2 body surface/dose. Follow-up ranged infection or surgery; strict follow-up and weekly/bimonthly clinical surveillance was from 5 to 16 months (a mean of 8.7). After introduction of MMF therapy, CsA dose could maintained during the first years of life. Catch up growth during peritoneal dialysis and be reduced from 4.3 to 2.9 mg/kg/24 h (p=0.008) and improvement of renal function was after transplantation was according the genetic target.In conclusion, management of CNS observed: cystatin C level decreased significantly (p=0,01). One patient presented with with intensive nutritional support (nocturnal gastric tube feeding), Ace inhibitor and cytomegalovirus infection, no other side-effects were observed.Conclusion: Introduction of aminoacid supplementation (oral and intraperitoneal) offered a treatment option without MMF allows a reduction of CsA dose with improvement of renal function estimated by nephrectomy, reducing also the need for albumin infusions and hospitalisation after the first cystatin C. A combined CsA and MMF therapy can be safely used in children. 6 months of life. Growth was preserved and transplantation could be delayed until 4 years of age and ESRD even after puberty.

COD. PP 71 COD. PP 72 Diuresis and functional bladder capacity, compared in school-age URODYNAMIC DYSFUNCTIONS AND RENAL DAMAGE IN THE children with and without nocturnal enuresis PATIENTS WITH DIURNAL ENURESIS K Van Hoeck 1, A Bael 1, H Lax 2, H Hirche 2, E Van Dessel 1, D Van Renthergem 1, J D O Tolunay*,N Buyan**,O Tan***, S Bakkaloglu**, O Soylemezoglu** * Gazi University, van Gool 1 [1] Department of Pediatrics, University Hospital Antwerp, Antwerp, Belgium Dept. of Pediatrics ** Gazi University, Dept of Pediatric Nephrology *** Gazi University, [2] Institute of Medical Informatics, Biometry and Epidemiology, Essen University, Essen, Dept of Urolo gy Presenting Author: N Buyan Germany GAZI UNIVERSITY , SCHOOL OF MEDICINE , DEPT. OF PEDIATRIC Dept Pediatrics Univ Hosp Antwerp , wilrijkstraat 10 , 2650 Edegem , Belgium NEPHROLOGY, BESEVLER , 06500 ANKARA , Turke y

Aim:‘Nocturnal functional bladder capacity’ and ‘nocturnal urine output’ are considere d The organic pathologies specifically urodynamic abnormalities are more common in the pivotal in the pathophysiology of Monosymptomatic Nocturnal Enuresis (MNE). The patients with diurnal enuresis than monosymptomatic nocturnal enuresis. relation of bladder volume and the preceding diuresis at spontaneous daytime voiding, the first void in the morning and bedwetting voidings was never studied. We compared it in 76 Objective of study: To evaluate the urodynamic abnormalities and the renal parenchymal prepubertal children with MNE to 50 controls. scarring in the pediatric patients with diurnal enuresis. Methods: For 48 h every voided volume was collected. The first voiding after a dry night was defined early morning volume (EMV), bedwetting volume (BWV) was measured using Method and material: Thirty patients ( 24 girls; mean age 7.85± 1.85 yrs, 6 boys; mean age alarm and diaper plus residual voiding. Any other voiding was defined voided volume 7± 1.04 yrs) diagnosed with diurnal enuresis were enrolled this study. The video- (VV). Creatinine clearance and plasma creatinine assumed constant, urinary creatinine urodynamic studies and the Tc-99m DMSA scan were performed. concentration was measured as a reciprocal for diuresis. Diuresis was also calculated from volume and time since last voiding. Forced micturition volume (FMV) was the largest Results: The findings were as fallows :unstable bladder: n=10, low volume capacity n=5, voiding following forced diuresis (water load of 20 ml/kg) and holding. low bladder compliance:n=2, both unstable bladder and low bladder capacity:n=6, VUR: Results: The relation of volume voided with preceding diuresis is different only at n=4,and normal video urodynamy findings:n=2. Since the participation in video dynamic bedwetting. At any urine output rate, BWV compare to all other VV rather than EMV; study, was not allowed by the families of three patients, only the uroflowmetric study was being significantly smaller (130ml, 95%CI 88-176) than EMV. In children with MNE, performed on these patients and the results were normal. The DMSA findings of the 30 FMV and EMV are significantly smaller. Urine production returns to baseline diuresis of patients revealed that 12 patients (40%) had normal findings, whereas renal scarring was 0,7 ml/kg/h one hour after bedtime in both populations. observed in one patient (3.33%). Hypoactive areas occurring secondary to previous Conclusion: Independent from diuresis, bedwetting occurs at a small volume -comparable infections were observed in both kidneys of 11 patients and in the left kidneys of six to a daytime voiding. In normal children and in occasional dry nights in children with MNE, patients. In the patients with the abnormal DMSA scan findings, 12 had recurrent urinary increased detrusor inhibition allows postponing voiding and accommodating a larger range tract infections and three had VUR. of urine output as EMV. Conclusion: In our study, since only 40% of the patients had normal DMSA scan findings and 92% had urodynamic abnormalities, it can be concluded that the patients with diurnal enuresis should be evaluated carefully for urodynamic abnormalities and renal parenchymal scarring. 1540 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 73 COD. PP 74 Urodynamic findings in children with nocturnal enuresis THE CONCEPT OF HABITUAL URINARY RETENTION (HUR) - A S Charalambous 1, N Prinza 2,Ch Thamnopoulos 1, F Papachristou 2, K. Tsakas 3,V. PAEDIATRIC UNDERSTANDING OF BLADDER DYSFUNCTION - Rombis 1, E. Ioannides3 1.Urology clinic, Hippokratio Gen. Hospital , Thessaloniki, 25 YEARS LATER Greece 2.1st Pediatric Clinic, Aristoteles University, Thessaloniki 3.Urology clinic, D Anders*, D Bölter Childrens Hospital University of Giessen, Germany Aristoteles University, Thessaloniki , Willaringen 38 , D-79736 Rickenbach , Germany Hippokratio General Hospital , Konstantinoupoleos 49 , 546 42 Thessoloniki , Greece Paediatric urology has changed over decades from operating "stenoses" to urodynamics and Aim: The objective of this study was to investigate the voiding dysfunctions in children recently outlining the "dysfunctional elimination syndrome" (Koff 1998) resembling the with Nocturnal Enuresis by urodynamics studies. concept we first presented 1981 (ESPN Antwerp). Material and methods: 49 children with nocturnal enuresis (31 boys and 18 girls), aged from 6 -14 years, were studied. Children with neurogenic bladder or structural urological Later our sample of 6 amounted to 180 girls with recurrent urinary tract infection (RUTI) abnormalities were excluded from the study. In all children the following parameters were and HUR as defined by 3 major criteria: abnormal uroflow pattern, significant residual, estimated:a) timetable of NE,b) ultrasound of urinary tract , (size of kidneys, bladder positive voiding history, and/or 3 minor criteria: constipation, wetting, reflux. capacity, bladder wall thickness , post voiding residual urine), c) Feeling/volume chart Age range: 2 to 15 years. Reflux:: 77 (43%). Diagnosis of HUR (including maximal bladder (frequency and biggest quantity of urination = functional capacity of bladder), and d) capacity, MBC) depends on examining the child after waiting for the end-diastolic phase at urodynamic parameters (uroflowmetry and water cytometry). Urodynamics findings imperative urge. Long term follow-up data (10 years)were obtained by questionnaire. correlated with findings from the rest control. From 49 children, 9 had mild NE (<3/ times per week), 9 moderate NE (3-6/ per week) and 31 serious NE (each evening). Daily enuresis Age distribution shows a minor peak at 4 and a major at 6-7 years probably reflecting was reported in 14/49 children. kindergarten and school entry. MBC values were amazing: e.g. 530 ml (age 4), 700 ml (age Results: Urodynamic findings were observed in all the children with serious NE and in 7). Masturbation with a full bladder may play a role, confirmed in 14 / 56 cases (25%). those with daily symptoms. These were instability of bladder, and abnormal uroflowmetry chape. Also, the functional bladder capacity in these children was found decreased, findings Therapy: counselling, scheduled voiding, double micturition, improved defaecation, that are also confirmed by the other parameters of control. The children with mild NE behavioral modification, cognitive training, flow-controlled biofeedback, no drugs except (<3/per week) had normal parameters both from Urodynamics and from the rest of the nitrofurantoin. Treatment of new (younger) patients is easier. If bladder function can be investigation. normalized reflux is no problem; surgery was rarely indicated (when bladder retraining Conclusions: The NE includes a spectrum of dysfunction in the nightly production of urine failed). and the functional capacity of urinary bladder, which seems to play an important role in the pathophysiology of NE. Findings from Urodynamic studies in children with serious NE and Conclusion: HUR is the main source of bladder dysfunction with retrograde effects. The those with daily symptoms shows that it has a useful role in NE management. approach described is a nearly perfect instrument to prevent RUTI, renal damage, wetting thereby cutting down expenses for drugs, high tech imaging, operations. HUR is related to avoiding public toilets, sort of a civilization disorder.

COD. PP 75 COD. PP 76 MEGACYSTIS-MICROCOLON-INTESTINAL HYPOPERISTALSIS THE EFFECT OF ANTIBIOTIC PROPHYLAXIS ON THE RATE OF SYNDROME (MMIHS) URINARY TRACT INFECTIONS IN CHILDREN WITH T Šuláková, H Vlèková, A Šuláková, A Bosáková, J Slaný, T Waloschek1, R Škába2 Dpt. DYSFUNCTIONAL VOIDING DISORDERS of Paediatrics University Hospital Ostrava, 1Dpt. of Pathology University Hospital Ostrava, S Tugay, H Usluer, C Caglayan, Z Bircan 2Dpt. of Paediatric Surgery, 2nd Medical School, Charles University in Prague Kocaeli University , Kocaeli University Faculty of Medicine Pediatric Nephrology Dpt.of Paediatrics, University Hospital Ostrava , Tr. 17.listopadu 1790 , 708 52 Ostrava , Department Umuttepe , 41380 Kocaeli , Turkey Czech Republic Dysfunctional voiding disorders cause recurrent urinary tract infections (UTI). The aim of MMIHS is rare disease characterised by urinary bladder distension with non-obstructive this study is to analyze the rate of recurrent UTI, and effectiveness of the three different voiding lesion and microcolon with reduced or absent peristalsis. The syndrome is also prophylactic agents (trimethoprim sulphamethoxazole (TM-SM), nitrofurantoin, associated with small intestine shortening and malrotation. cephadroxil) in children followed with dysfunctional voiding disorders in our clinic from We report one patient with MMHIS. The girl was born 6 weeks premature by caesarean 2002 to 2006, retrospectively. section. Her neonatal period was complicated by respiratory distress and megacystis Ninety-six patients aged 6.19 ± 4.09 years with dysfunctional voiding disorders were (catheterization, epicystostomy, urinary tract infections – UTI). She was repeatedly enrolled in the study. Total follow-up period was 42498 days and total infection numbers admitted into a hospital due to failure to thrive, problems with bowel movements, were 329. The infection rate was calculated as 0.7 in 100 patient days. pyelonephritis and bladder dysfunction during the first year of life. When she was 7 months The infection free mean time passed during TM-SM prophylaxis before the first infection old, sigmoideostomy and enterostomy were made due to ileus. We excluded Hirschsprung was 126.61± 312.69 days with an infection rate of 2.5 in 100 patient days. The infection disease and cystic fibrosis and concluded the patient’s state as suspected MMIHS. We ha d free mean time passed during nitrofurantoin prophylaxis before the first infection was to deal with several crucial problems during her 3 years of lifetime: (1) nutrition intake 95.87±95.42 days with an infection rate of 0.8 in 100 patient days. The infection free mean (home parenterale nutrition), (2) recurring peristalsis failure – 5 surgeries during 18 months, time passed during cephadroxil prophylaxis before the first infection was 141±127.74 days (3) bladder evacuation (finally clean intermittent catheterization) and preservation of renal with an infection rate of 1.3 in 100 patient days. Although infection free mean time passed function, (4) recurring UTI, (5) recurring catheter sepsis and central venous line thrombosis, during prophylaxis before the first infection was not statistically significant between these (6) carrying for stomies, (7) family instruction in taking care of the girl at home. The girl’s three drugs, infection rate under prophylaxis was statistically significantly low with state was failing all the time and she died of the septic shock in connection with multiorgan nitrofurantoin and cephadroxyl. failure at the age of 3 years. It was concluded that although antibiotic prophylaxis is not a way of definite protection in Conclusion: MMIHS is very rare congenital disorder. The aetiology is unclear and dysfunctional voiding disorders, nitrofurantoin and cephadroxil are the most effective ones prognosis is bad. The sick patients die generally at first year of life. in this manner. Pediatr Nephrol (2006) 21:1493–1635 1541

COD. PP 77 COD. PP 78 PREDICTIVE VALUE OF CLINICAL AND LABORATORY URINE CONCENTRATION OF FIBRONECTIN (FN) AND PARAMETERS FOR THE PRESENCE OF VESICOURETERAL TRANSFORMING GROWTH FACTOR – BETA1 (TGF-BETA1) IN REFLUX IN CHILDREN WITH URINARY TRACT INFECTION CHILDREN WITH VESICO-URETERAL REFLUX A Soylu, B Kasap, K Demir, M Turkmen, S Kavukc u A Sabasiñska, W Zoch-Zwierz A Wasilewska , CamliCay Mah. 5182 Sk. No:112/A Urla , 35315 Izmir , Turkey I Department of Pediatrics, Medical University in Biaùystok, Poland , Waszyngtona 17 , 15- 274 Biaùystok , Poland We aimed to determine predictive clinical and laboratory parameters for the presence of vesicoureteral reflux (VUR) in children with urinary tract infection (UTI). Vesico-ureteral reflux (VUR) predisposes to interstitial fibrosis renal scarring. Fibronectin, Data of patients with a history of proved UTI who underwent voiding cystouretrography the protein of intracellular matrix and transforming growth factor beta 1 play very important (VCUG) between 1990 and 2005 were evaluated retrospectively for the clinical and role in this process. laboratory parameters. Children with VUR (Group 1) vs no VUR (Group 2) and children Aim of work was the assessment of urinary concentration of FN and TGF-beta 1 in children with high grade VUR (Group 3) vs low grade or no VUR (Group 4) were compared. with VUR. Material and methods: The examined group consisted of 60 children with VUR, which was There were 147 patients (46 M; mean age 4043 months). Group 1 (n: 91) and Group 2 diagnosed in miction cystography. The children were divided into three subgroups: A – 20 (n:56) were similar except higher UTI number, pyuria (Q 25/hpf) and CRP levels in Group 1. children with II degree, B – 20 children with III and C – 20 children with IV and V degree A CRP level of 23.5 mg/L was the best cut-off value predicting VUR (0.65±0.71; %95 CI of VUR, according to International VUR Study Committee. Control group) consisted of 28 0.514–0.793, p=0.04). Group 3 (n=62) had higher fever and CRP rates than Group 4 (n=85). healthy children at the same age. A CRP level of 50 mg/L was the best cut-off value predicting high grade VUR (0.79±0.70; Urinary concentration of FN and TGF-beta1 was assessed by immunoenzymathic method 95% CI 0.653–0.928, p=0.01; sensitivity 73%, specificity 69%, PPV 42%, NPV 76%, OR (f. Tacara and R&D). 6.0). If VCUG was not performed based on this cut off CRP level, then 27% of the children Results: In children with VUR urinary concentration of FN was 224.1 (15.7 – 3777.5) with high grade VUR would have been missed, but 69% of the children in Group 4 would pg/mg cr. and TGF – beta1 concentration 114.1 (4.64 – 3372.9) pg mg/cr. The values were be free of VCUG. higher than in control group (p<0.01). Urinary concentration of TGF-beta1 increased together with the VUR degree and in all subgroups of ill children was higher than in Recurrent VUR and high CRP levels are predictive for the presence of VUR and high grade controls (p<0.01). However urinary concentration of FN was increased only in subgroup C VUR respectively. These parameters could be helpful in managing children with UTI (p<0.01). A positive correlation between urinary concentration of FN and TGF-beta1 was eliminating the need for invasive procedures like VCUG. found (r=0.416, p<0.05). The urinary concentration of FN and TGF-beta1 was proportional to number of refluxes and frequency of urinary tract infections Conclusion: Urinary concentration of FN increases in children with high VUR degree and correlates with urinary TGF-beta1.

COD. PP 79 COD. PP 80 Is reflux missed on fluoroscopic voiding cysteourethrography and Minimizing Urinary Tract Infection (UTI) investigation - Can renal demonstrated only by contrast-enhanced voiding urosonography scarring be predicted by clinical data? clinically important? Maria do Céu Ribeiro, Susana Pissarra, Ana Oliveira, José Pedro Patricio, Helena Jardim AAnthopoulou(1), F Papadopoulou(1), E Siomou(2), A Fotopoulos(3), J Al Bokhrhli(3), O , Rua António Patricio 104 R/C esq , 4460-204 Sra da Matosinhos , Portugal Katsios(1), S C Efremidis(1) (1): Radiology Department (2): Pediatric Clinic (3): Nuclear Medicine Department Presenting Author: AAntho poulou To date the DMSA scan has been the ‘gold standard’ for the diagnosis of pyelonephritis University Hospital of Ioannina , Solomou 6 , 45221 Ioannina , Greece associated renal scarring. In an attempt to reduce the number of investigations, we studied the relationship between acute phase reactants and DMSA results in a population of 64 Purpose:Contrast-enhanced Voiding-Urosonography(CE-VUS) has been found with highe r children with a first proven acute pyelonephritis. Gender, age, fever, leukocytosis and C- sensitivity compared to Fluoroscopic-Voiding-Cysteourethrography(VCUG).The purpose reactive protein (CRP), renal ultrasound and early and late (6 months) DMSA scanning of our study is to evaluate the clinical importance of reflux missed on VCUG and were analysed. demonstrated only by CE-VUS by assesing its relationship with renal damage on renal Median age was 14 months and forty (63%) were girls. Twenty (31%) were febrile longe r cortical scintigraphy(DMSA). than 2 days before diagnosis. Median CRP was 61 mg/L and 63 (51%) showed leukocytosis. E. coli was identified in 50 (78%), other agents in 7 (11%) and in the Materials and Methods:A total of 152 refluxing children on either VCUG or VUS(65 males, remainder (7) no agent was found. Acute DMSA showed defects in 43 (67%) which had 87 females, median age: 1.16 years)were also studied with DMSA 6 months after the first resolved in 12 (28%) by 6 months. There was a predominance of females with acute DMSA proven UTI.Ninety-nine of them had VUR on both examinations(controls) while the defects (p= 0.008) with a positive correlation with age (p=0.03). There was no gender remaining 53 ones only on VUS(study group).VUS was performed with harmonic imaging difference in late DMSA evaluations. Age, leukocytosis, CRP were not related to the and a 2nd generation US contast-agent.Children with kidney abnormalities associated with severity of renal damage in either assessment. VUR were excluded from the study. Statistical analysis included McNemar’s, chi-square, t- In our study, girls were found to have a higher risk of acute DMSA defects after a first Student’s and Fisher’s tests. Results were analyzed according to age (<2yrs, >2yrs). documented pyelonephritis, but the late imaging showed no difference. Long standing fever and acute phase reactants were not associated with early or late changes in DMSA results. Results: Renal damage was found in 15/53 children(28%) in the study group (15/66 In conclusion, the DMSA remains superior to clinical and biological data in identifying refluxing KUU) and in 37/99 children(37%) in controls (38/144 refluxing KUU), [p=0.7]. patients at risk of transitory or permanent renal damage after acute pyelonephritis. No significant relationship was found between renal damage and severity of VUR in both groups, although renal damage was more common in higher grades of reflux. The incidence of scar formation was more common in children <2yrs(37/98, 38% vs 15/54, 28%, p=0.3).

Conclusion: 1)Reflux missed on VCUG and demonstrated only on CE-VUS is associated with similar incidence of renal damage compared to ordinary reflux shown by VCUG. 2) Renal damage is found more often in higher grades of VUR and tends to be more common in younger age children(<2yrs). 1542 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 81 COD. PP 82 The Effect of Probiotic Prophylaxis for Preventing Recurrent Urinary The Clinical Characteristics of Infantile Primary Vesicoureteral Reflux Tract Infection in Children with Persistant Primary Vesicoureteral and Its Spontaneous Resolution Rate Reflux YH Shim, YS Chae, JH Kim, SJ Lee Department of Pediatrics, College of Medicine, Ewha Lee SJ*, Kim HJ, Shim YH, Lee JW Womans University Ewha Womans University Hospital , Dept of Pediatrics, #911-9 Mokdong, Yangcheonku , Department of Pediatrics, Ewha Womans University Hospital , Dept. of Pediatrics, Ewha 150-710 Seoul , South Korea Womans University Mokdong Hospital, #911-1, MokDong, YangCheon-Kum, Seoul, Korea , 158-710 Seoul , South Korea Purpose : Probiotics, beneficial living microorganisms, have been shown to be effective in preventing infectious gastroenteritis but its effect in preventing urinary tract infection(UTI) Purpose: The primary vesicoureteral reflux (VUR) in childhood is in general, more is not known. Prospective randomized controlled study was done to compare the preventive prevalent among girls, has various degrees of reflux or renal scar, and surgery has been effect of probiotics with antibiotic prophylaxis in children with persistent primary recommended in severe VUR because of its low resolution rate. In contrast, neonatally vesicoureteral reflux(VUR) diagnosed primary VUR is more prevalent among boys, tends to have more severe reflux Patients and Method : 75 children with persistent primary VUR after one year’s and renal scarring, but surgery is usually withheld even in severe VUR because of the much trimethoprim-sulfamethoxazole(TMP/SMX)) prophylaxis were randomly allocated into higher resolution rate. The present study examined the characteristics of infantile primary probiotic or antibiotic prophylaxis group during the next year. We observed the incidence o f VUR. recurrent UTI and evaluated the difference of UTI incidence after stratified by the kwown Subjects and Methods: 96 infants with primary VUR, diagnosed after their first UTI at risk factors. Ewha Womans University Hospital (1995-2004) were retrospectively reviewed. Results : The recurrence rate of UTI were 18.9% (7/37) in probiotics group, which was not Radionuclide voiding cystourethrogram was taken annually for 3 years after the diagnosis. different to 21.2%(8/38) of control group. Even after stratification by VUR grade, age, The clinical characterristics including gender difference, the degree of VUR or renal scar gender, phimosis and renal scar, the difference of UTI incidence was not significant and spontaneous resolution rate were evaluated. between two groups. Conclusion : The incidence of recurrent UTI in probiotic prophylaxis Results: Infantile primary VUR was four-fold prevalent in boys compared to girls (79.2% vs group was not different to that of antibiotic prophylaxis group in children with persistent 20.8%). The distribution of VUR grades was not different between boys and girls (P>0.05). primary VUR. The percentage of renal scar was not different between boys and girls, but the percentage of atrophic scarred kidney was significantly higher in boys than in girls (17.2% vs 3.4%) Key words: Persistent primary VUR, Antibiotic prophylaxis, Probiotics , Recurrent UTI (P<0.05). Final resolution rate in 3 years was not different between boys and girls. But the resolution rate of severe VUR in the first year was significantly higher in boys than girls (40% vs 5%)(P<0.05). Conclusion: Infantile primary VUR and atrophic scarred kidney were more prevalent among boys. The spontaneous resolution rate was very high in the first year, even in severe VUR with atrophic scarred kidney.

COD. PP 83 COD. PP 84 Effect of Lactobacillus isolates on the urinary tract pathogens to infants FOLLOW-UP OF HIGH GRADE VESCICO-URETERAL REFLUX in vitro. DIAGNOSED BY COLOUR-DOPPLER CYSTOSONOGRAPHY I.S.Lim, K.W.Yun(presenting author), H.S.Lee, W.Y.Kim Department of Pediatrics, WITH ECHOCONTRAST Chung-Ang University College of Medicine, Seoul 156-756 Korea R Chimenz, G Conti, L Silipigni, R Gallizzi, A Distilo, C Fede Paediatric Nephrology and Department of Pediatrics, Chungang University Yongsan Hospital , Department o f Dialysis Unit, University of Messina Pediatrics, Chungang University Yongsan Hospital, 65-207, Hangangno 3(sam)-ga , 140- University of Messina , Paediatric Nephrology and Dialysis Unit, via Consolare Valeria , 757 Seoul , South Korea 98100 Messina , Italy Italy

Urinary tract infections are common clinical entities occurring in a variety of patient Overall resolution rate of low-moderate grade vescico-ureteral refluxes (VUR) is known. groups, most frequently caused by uropathogenic Escherichia coli. Urinary pathogens For this, we investigated the factors that could influence the prognosis of the high grade almost always infect the host through ascension from the rectum, vagina to the urethra and VUR. bladder. Likewise, the Lactobacillus that predominate in the vagina of healthy women, This study comprised 54 infants (30 boys and 24 girls) with age between 7 days and 7.2 spread from the rectum and perineum and form a barrier in the vagina to bladder entry by years. All patients presented high grade VUR (3°grade as colour-doppler cystosonografy uropathogens. Lactobacilli were isolated from 10 Korean UTI infants’ stools and examined with echo contrast (CSG) =from 4° to 5° grade as voiding cisto-urethograph). Bilateral for their potentially antimicrobial properties against 24 strains of pathogenic bacteria. reflux was seen in 28% of cases. The majority of patients (58%) were diagnosed after Examined supernatants from Lactobacillus broth cultures supernatants demonstrated major recurrent urinary tract infections (UTI), 29% after acute pyelonephritis (APN) and 13% antimicrobial activity against UTI E. coli isolates, E. coli 0157 H7 ATCC 43894, Shigella after ultrasonografy that indicated a mild-severe grade hydronephrosis. Patients were flexneri KCTC 2008 and Bacillus anthracis ATCC 14185. Some isolates, which are in vitro followed with repeated CSG after one year from diagnosis. antagonistic against enteropathogenic bacteria may be considered as potential candidates for In 25 children (46%) VUR spontaneously resolved, while there was not difference of rate in probiotics, especially in controlling urinary tract infection caused by uropathogenic E. coli. the remaining 54% (52% bilateral and 48% unilateral reflux) children with 3°grade VUR. The spontaneous resolution was not influenced by concomitant presence of kidney dysplasia o by gender, while it decreased in children after 3 years-old. There was not correlation between clinical presentation (UTI and APN) and reflux resolution. More of 50% of children with VUR persistence had a mild-severe grade hydronephrosis, but the difference was not statistically significant (OR 1,81 IC 0,611-5,39). In conclusion, our data do not evidence previously factors that influence the resolution of the high grade VUR. Pediatr Nephrol (2006) 21:1493–1635 1543

COD. PP 85 COD. PP 86 A study of impact of delayed treatment on renal injuries in pediatric Children referred to outpatients from primary care with urinary tract urinary tract infections infection: do they all need investigation? *M Sharifian, M Rajabnejad, A Karimi, M Mohkam, R Dalirani. A R Watson, A Lunn Shahid Beheshti University of Medical Sciences , Mofid Children Hospital, Shariati Ave, , Nottingham University Hospitals , Children & Young People`s Kidney Unit, City Hospital 1431943935 Tehran , Tehran Iran Campus, Hucknall Road , NG8 1LB Nottingham , UK

OBJECTIVE: The aim of this Study was to determine whether the delay in treatment of Background and Methods: children with urinary tract infection could predict the risk for renal damage as evaluated by The current dogma is that all children with a proven UTI need investigation but algorithms Dimercaptosuccinic acid (DMSA) Scan performed 6 months after the infection. fail to differentiate between those with lower tract (LT) from upper tract (UT) involvement. PATIENTS and METHODS: The study population included 100 children aged 1 month to We prospectively collected data on 195 consecutive UTI referrals from primary care (GPs) 14 years who admitted with urinary tract infection in Mofid Children`s Hospital from to a single general paediatric clinic. We classified the infection clinically as UT (fever, March 2000 to September 2004. DMSA renal scan was performed in all patients at the abdominal or loin pain, or LT (dysuria, frequency, enuresis, lack of systemic symptoms). beginning of treatment to confirm the diagnosis and evaluate the extension of renal All patients underwent detailed ultrasound of the renal tract (USS). involvement. All patients were treated with third generation cephalosporin (Ceftriaxone). Results: Twenty seven patients proceed to perform DMSA Scan 6 months after treatment for 195 children (41 male) were seen in the clinic with a mean age of 4.8yrs (range 0.1- evaluation of scars. 14.7yrs). 9 children (4.6%) had an abnormality on USS of which only 3 were clinically RESULTS: Of 100 patients studied, 77 were girls and 23 percent were boys. The mean age significant after further investigation. 128 (66%) children were classified as having LT and was 3 years and 3 months (Range 1 month to 14 years). Organisms responsible for UTI only 4 of 128 (3.1%) had an abnormality on USS compared to 5 of 67 (7.5%) classified as were E.coli in 68%, Streptococcus in 14%, Pseudomona in10%, Klebsiella in 6% and having UT. 181 children with a normal USS were discharged after the initial visit. 15 Candida in 2% of cases.The mean time of delay to start treatment was 4.6 days. After 6 (8.3%) returned with UTI symptoms and the majority of these patients have since been months; 51.9 percent of patients who were treated after 2.8 days had normal DMSA Scan discharged. If we restricted investigations to those <2yrs of age or those who had UT and 33.3 percent of patients who were treated after 6 days had renal Scarring as evaluated features or recurrent UTIs or a positive family history then 76/195 children would have by DMSA Scan. been referred for USS and 5 (6.6%) would have been abnormal. All those with clinically CONCLUSION: Efforts to reduce the incidence and severity of renal scarring should be significant abnormalities would have been identified. directed towards rapid diagnosis and effective early management of urinary tract infections Conclusions: in infancy and childhood. There is a low incidence of USS and clinical abnormalities of the urinary tract in children routinely referred to outpatients with UTI from primary care. The study questions our current recommendation of referral for UTI, especially in older children with LT symptoms.

COD. PP 87 COD. PP 88 New nitrofuran derivates in UTI: 5-year pediatric experience. Vesicoureteral reflux in children with prenatal suspicion of urinary V Strazdins I Andersone tract abnormalities University Hospital for Children , Nephrology department , LV-1004 Riga , Latvia G Krzemien, M Roszkowska-Blaim, I Kostro, A Szmigielska, J Wojnar, R Sekowska, A Kaminska INTRODUCTION. Nitrofuran derivates (NFD) are effective in low concentrations and Department of Pediatrics and Nephrology, Medical University of Warsaw , Department o f against resistant bacteria; resistance develops slowly and never reaches high degree; they Pediatrics and Nephrology, Medical University of Warsaw , 00-576 Warsaw , Polan d has wide activity range and are commonly used in treating UTI. “Old” NFD, synthesized 50 years ago, have side-effects: skin irritation and gastrointestinal disturbances, reducing use in Aim: To estimate the frequency of vesicoureteral reflux (VUR) in children with prenatal pediatrics. The new NFD, Furazidinum, synthesized in Latvia in 1986, when 1st tested suspicion of urinary tract (UT) abnormalities. clinically, showed no side effects! It is 5 times less toxic vs. Furadoninum with Material and methods: 93 children (64M/29F) with prenatal suspicion of UT abnormalities bioavailability 5 higher vs. Furaginum. We use it from 2001. OBJECTIVES. Efficacy were diagnosed in our department between 1997-2005. Prenatal ultrasonography (US) was evaluation; frequency of side-effects; resistance against UTI-causing agents. PATIENTS. performed between 18-41 week of gestation (mean 32,65,6). Congenital anomalies of UT 83 patients aged from 0 to 21 years treated with Furazidinum were analyzed retrospectively were suspected when dilatation of renal pelvic diameter (RPD) was 4mm before 33 (01.01.2001-31.12.2005). 51 (61%) has normal renal function, 32 (39%) has chronic renal weeks, 7mm after 33 weeks or other abnormalities in US were observed. Postnatal US failure. There were 10.527 total patient days on Furazidinum. METHODS. Furamag dose: was done between 1-122 days of life (mean 18,221,5), voiding cystourethrography 25 mg single bed-time dose for 0-2 years old (6 patients), and 50 mg single bed-time dose (VCUG) between 1 day to 13 months (mean 2,12,3 months). RPD >5mm in postnatal US for other 75 patients. 7.147 urine cultures (BACTEC) analyzed on 5 antibacterial agents and was regarded as abnormal. 5 bacterial species. RESULTS. Efficacy and safety of the drug were proven: only 3 Results: UT dilatation in prenatal US was detected in 82 (88%) children, other changes of withdrawals due to inefficacy (3,61%), and 1 case of gastrointestinal side-effects (1,20%), UT in 11 (12%). Normal US was observed in 9 (10%) children, abnormal in 84 (90%): no skin reactions. Bacterial sensitivity remained unchanged for 3 species and increased for dilatation of UT in 100 renal units, duplex kidney -12, multicystic dysplastic kidney -7, 2 species (Figure 1). Other antibacterial agents dramatically increased resistance rate. ureterocele -3. VUR was detected in 20 (21,5%) children to 28 kidneys (I-IIIo -18 kidneys, DISCUSSION. We confirm Furamag low side-effect rate and the unchanging resistance and IV-Vo -10). Dilatation of UT in prenatal US was observed in 18 (64,3%) renal units with suggest its use as safe and effective UTI management in pediatric population. VUR, normal US in 10 (35,7%). Abnormal postnatal US was noted in 22 (78,6%) renal units with VUR (dilatation of UT -19, another anomalies -3), normal in 6 (21,4%). Conclusions: VCUG should be considered in all children with prenatal suspicion of UT abnormalities, because of high frequency of VUR in this group. Normal prenatal/postnatal USG does not exclude presence of VUR. 1544 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 89 COD. PP 90 OXIDATIVE STRESS AND ANTIOXIDANT VITAMIN IN THE INCIDENCE OF URINARY INFECTION IN INFANTS WITH PYELONEPHRITIS OR WITHOUT ABNORMAL FETAL ULTRASOUND M ESPINO (1), A GRANADOS (1), B BONET (1,2), M VIANA (2), F CAVA (3), MA S Flajsman-Raspor, M Subat-Dezulovic, G Saina, T Grbac, A Smokvina Presenting Author: MARTINEZ GRANERO(1), C MOLINA (1) (1)FUNDACION HOSPITAL ALCORCON. S Flajsman-Raspor PEDIATRICS AND NEONATOLOGY DEPARTMENT. ALCORCON. MADRID. Clinical Medical Center Rijeka , Children`s Hospital, Dept of Pediatric Nephrology , +385 SPAIN. (2)UNIVERSIDAD SAN PABLO. CEU. MADRID. SPAIN. (3) FUNDACION RIJEKA , Croatia Croatia HOSPITAL ALCROCON. BIOCHEMICAL DEPARMENT. SPAIN. PRESENTING AUTHOR: M ESPINO The aim of this study was to establish if the fetal ultrasonography (FUS) comprehends to FUNDACION HOSPITAL ALCORCON , PEDIATRICS AND NEONATOLOGY , 28922 the diagnosis of urinary tract infection (UTI) or earlier detection of urologic anomalies MADRID , Spain (UA). MATERIALS AND METHODS: We retrospectively analyzed a group of 246 children aged Free radicals generation is a phagocytes response againts infections. Free radical lipid 0-12 months, 116 (47%) girls and 130 (53%) boys who referred for the first investigation of peroxidation is one of the major reasons for tissue damage. Pyelonephritis sometimes leaves the urinary tract in the period of 1997 – 2005. UTI was diagnosed based on the standard permanent tissue damage. Vitamins A and E are antioxidants which prevent free radicals investigation of urine sediment and proven bacteriuria. In all children abdominal ultrasound generation in infections. (US) was done; in children with FUS suspected anomalies on day 3 to 5 and second 3 to 5 AIM weeks postnatally. Vesicoureteral reflux (VUR) was investigated by voiding To study free radicals lipids peroxidation and to determinate vitamin A and E levels in cystourethrography. Based on sonographic findings, other radiologic or radionuclide studies children with pyelonephritis and compare with other infectious diseases. (dynamic MAG3 or static DMSA scintigraphy) were performed. Results were expressed as PATIENTS AND METHODS percents of total and significance was tested by t-Test. RESULSTS: UTI was diagnosed in We include 41 children with fever, with blood and urine sample as sepsis work-up. 29 173 children. The mean age of the first UTI was 3.9 months in the group with pathologic children had pyelonephritis (P) and 12 children other infectious disease (C). We FUS (32/173, 19%) compared to 6.5 months in patients with normal FUS (p 0.0005). UTI determinated vitamin A and E levels in blood sample and tiobarbituric acid reaction with underlying malformation experienced in total 84 children, 26 (31%) of them sustances (TBARS) in urine. Results are presented as mean + standard error (SE); we predominantly boys (22/26) with abnormal FUS average age was 3.78 compared to 5.73 compare mean with t-student test; correlation coefficients with Pearson function. months in the group with no FUS presumed anomalies (p 0.03). RESULTS CONCLUSON: Based on our study we can conclude that children with FUS presumed Mean aged in children with P 9,37 months (SE 1,4), in children with C 11,29 ( SE 2,8). urologic anomalies benefit from earlier detection of UTI and urologic anomalies making Mean vitamin A levels in P 36,82 (SE 2,36); in C 35,89 (SE 3,85). Mean vitamin E in P possible the prevention of further renal damage. 984,02 (SE 45,33) and in C 896,01(SE 58,46). Means pcr in P 51,07 (SE7,14), in C 57 (SE 23) (p<0,001). MADO/creatinine levels in urine sample in P 0,20 (SE 0,12) and in C 0,16 (SE 0,16). Significant positive correlation were found between vitamin A and E. Significant negative correlation between vitamin A and pcr. CONCLUSIONS Plasmatic levels of antioxidant vitamins A and E and oxidative stress parameter, TBARS, are similar between chidren with pyelonephritis and other infectious disease.

COD. PP 91 COD. PP 92 CLINICAL AND GENETIC FACTORS CONTRIBUTING TO Procalcitonin as a marker of renal scarring in young children after RENAL SCARRING IN CHILDREN WITH VESICOURETERIC acute pyelonephritis. REFLUX Orùowska H, Roszkowska-Blaim M, Krzemieñ G. T Baltesova 1, L Podracka 1, J Salagovic 2, D Potocekova 3, Z Kurcinova 4, J Takacs 5, M , Department of Pediatric Nephrology, Warsaw , 00-576 Warszawa , Polan d Verebova 6 1 Department of Paediatrics, 2 Department of Medical Biology, 3 Department of Biostatistics, Safarik University, Kosice, Slovakia, 4 Department of Urology, 5 Institute The aim of this study was to determine the accuracy of serum procalcitonin (PCT) of Nuclear Medicine, 6 Department of Radiology, University Hospital, Kosice, Slovakia measurements to predict the risk of renal scaring in children up to 2 years with acute 1st. Department of Paediatrics, Safarik University , Trieda SNP 1 , 04066 Kosice , Slovak pyelonephritis (APN). Republic The study comprised 54 children aged 6 weeks to 23 months (mean 7,2± 5,34 months) having a first APN as assessed by 99mTc-DMSA scintigraphy (DMSA) performed in the Aim: To evaluate the development of renal functions and scarring in children with primary first 10 days after admission. After 6 months DMSA examination was repeated. Afte r vesicouretric reflux (VUR) in relation to the persistence of VUR, the frequency of acute admission PCT level was measured using an immunoluminometric assay (LUMITEST pyelonephritis (APN), the distribution of angiotensin-converting enzyme (ACE), PCT, Brahms Diagnostica) and it was compared with other inflammatory markers: C- angiotensinogen (ATG) and angiotensin type 1 receptor (AT1R) genotypes. reactive protein (CRP), erythrocyte sedimentation rate (ESR), leukocyte counts (LC) and Patients and methods: 5-year follow-up was performed in 41 children (15 boys) with VUR neutrofile counts (NC). Data are expressed as the medianSx. grade III.-V., mean age 8,7±3,9 year. 25 patients had bilateral VUR, 32 (78%) were treated 49 (90%) of 54 children had renal parenchymal damage (RPD). The mean serum PCT level, surgicaly and 9 were managed conservatively. The change in glomerular filtration rate CRP, ESR and NC were significantly higher in the group with RPD as compared to the calculated according to Schwartz formula (ÄGFR) was expressed as percentage of baseline healthy group, respectively: 1,3± 1,93 vs. 0,99±1,46 (p=0,03); 6,54±5,84 vs. 3,45±3,58 GFR. Renal scars were detected by repeated DMSA scan. I/D polymorphism of the ACE (p=0,004); 53,29±31,15 vs. 34±20,31 (p=0,001); 53,76±14,59 vs 44,91±17,86 (p=0,02). gene, M235T polymorphism of the ATG gene and A1166C polymorphism of the AT1 R There was no significant differences between groups in mean values of LC (19,8±8,03 vs gene were determined by PCR method 17,89±5,63 (p=0,235). Results: The decline of GFR during study period was present in 18 children (44%) with PCT measure can help in diagnosis of renal scarring in young children. mean ÄGFR -12,2%. GFR < 80 ml/min/1,73m2 was noticed in 6 children. Progressive renal scarring was found in 26 (63%) patients and was significantly related to the recurrent APN (> 2 episodes) (p=0,026, OR 3,7; CI 95% 1,14-12). Persistence of VUR had no significant impact on progression of parenchymal lesions. Genotype or allele frequencies of ACE, ATG and AT1R genes were not significantly associated neither with progressive scarring nor with declining character of GFR. Conclusion: Urinary tract infections are more important than genetic factors for the development of negative structural changes of renal parenchyme in children with VUR. Supported by Research Project VEGA 1/8297/01 Pediatr Nephrol (2006) 21:1493–1635 1545

COD. PP 93 COD. PP 94 LONG-TERM EVOLUTION OF RENAL DAMAGE ASSOCIATED Diagnostic of Chlamydia trachomatis in children with infectio tractus WITH UNILATERAL VESICO-URETERIC REFLUX (VUR) urinary. C Grassia, N Valentini, C Polito, C Santoro, L Graziano, E Palma, M Rea, A La Manna, G R Bednorz I Choroszy-Krol D Zwolinska D Polak-Jonkisz Lama Medical University, ul.M.Sklodowskiej 50/52 , Department of Pediatric Nephrology , 50- Dipartimento di Pediatria, Nefrologia Pediatrica, Seconda Università degli Studi di Napoli, , 369 Wroclaw , Poland Via L. De Crecchio, 4 , 80138 Naples , Italia Italy Chlamydia trachomatis ( C.trachomatis) is one of the primary etiologic factors of urinary Symmetrical damage in the function of both kidneys could not be recognized at tract infections in adults. Data to the point chlamydial urinary tract infection in children are dimercaptosuccinic acid (DMSA) scan when both kidneys are affected. Therefore, subjects sparse. The aim of this study was to evaluate the usefulness of the nested-PCR method in with renal damage associated with unilateral VUR represent a good model for studying the the indentification of DNA C.trachomatis in urine samples and qualification of correlation evolution of the damage with time. ferquency the indentification of chlamydial antigens in the swabs of urethra by DIF. The object of the study was group 38 from 195 patients, 24 girls and 14 boys aged since 6 month 71 children with unilateral primary VUR and ipsilateral renal differential uptake (DU) < to 18 years, with positive results of research from swabs of urethra in the direction 45% at DMSA imaging 6 months after the last urinary tract infection (UTI), underwent a C.trachomatis. DNA C.trachomatis was detected in sediment of urine samples of research further DMSA scan 5-24 yrs ( mean 8.6) later. Only 0.06 febrile UTI/yr on average group. Bacteriological tests were taked by direct immunofluorescence method using occurred during the follow-up period. Pathfinder Chlamydia trachomatis Direct Specimen tests by BioRad.Genetic research of urine samples was made by using diagnostic kit PCR-Chlamydia trachomatis by DNA DU of the refluxing kidney averaged 27.1% 1.2 SEM at first and 26.5% 1.3 (p = 0.39) Gdansk, based on amplificantion fragment of gene crp (cystein rich protein) C.trachomatis at last visit. In 14 pts (20%) a gain > 3% ( max 8%) DU of the refluxing kidney was in nested-PCR system. Final product 199bp was loaded in an agarose gel with ethidum recorded. None of the 14 had a DU > 45% at last visit. In 9 (13 %) pts a loss > 3 % DU of bromide. Positive results research by using PCR was determinated DIF tests was the refluxing kidney was recorded, with a loss > 10% in 4. Four out of the 18 pts with DU determinated by 34/38(89.4%)overall, 13/14(94.8%)boys and 21/24(87.5%)girls. 35-45 % at first visit (35, 38, 45 and 45 %, respectively) lost > 3% (4, 5, 13 and 27% Conformity results research in both tests was amount to 65.7%.In some cases we did not respectively) DU of the refluxing kidney. observed the correlation between positive results DIF from swabs of urethra and PCR from urine samples. Nested-PCR technique is expensive and labor-consuming method so PCR The improvement in DU of refluxing kidney is not the rule, is limited in extent and does not has limited employment in practice chlamydial diagnostics. There should be used nested- allow restoration to normal values. A mild reduction of DU (35-45 %) at diagnosis does no t PCR in cases of dificulty. exclude the event of subsequent significant loss, so indicating the need for long-term monitoring.

COD. PP 95 COD. PP 96 Is there a need for antibiotic prophylaxis after single bladder STOPPING PROPHYLACTIC ANTIBIOTICS IN CHILDREN WITH catheterization in otherwise healthy children? VESICOURETERAL REFLUX (VUR) RN Sukhai (presenting author) WJ Robbe WCG Plandsoen RN van der Plas MJA Malessy A La Manna, C Polito, M Rea, M Grimaldi, V Narciso, L Tafuro, N Valentini, C Santoro, R Pediatric Department , Leiden University Medical Center , 2300RC Leiden , The Del Gado Netherlands Dipartimento di Pediatria, Urologia Pediatrica, Seconda Università degli Studi di Napoli , Via L. De Crecchio, 4 , 80138 Naples , Italy Italy Abstract Background: The current standard of care in the management of VUR include prophylactic antibiotics on One hundred and seventy-five out of 200 otherwise healthy infants had an indwelling the belief that it is beneficial in the prevention of recurrent urinary tract infections (UTI) bladder catheter inserted during lengthily surgical reconstruction for obstetrical brachial and renal scarring; surprisingly, however, this belief lacks at present evidence. plexus palsy (OBPP). These children did not receive prophylactic antibiotics. True We reviewed the outcome of stopping prophylactic antibiotics in 119 children (91 females) incidence of urinary tract infection in this population might be very useful to elucidate the with primary persistent VUR without voiding dysfunction, mainly of them (71%) with relevance of prophylactic antibiotics after single bladder catheterisation in otherwise healthy dilated VUR at isotopic cystography. children. Mean followup was 2,6 years (0.5-10.7); overall rate of UTI during follow-up 18.4%. 8 children (7 females) had one febrile UTI (6.7%) whereas 14 (all females – in 3 more then Patients and methods: 1 episode) non febrile UTI (11.7%). Febrile UTI rate was low and strictly associated to We retrospectively studied the records of 175 out of 200 infants consecutively admitted dilated VUR (7/8). Overall rate of UTI was significantly (p= 0.04) higher in females. between January 2000 and July 15th 2004 for obstetrical brachial plexus surgery. All Discontinuing prophylactic antibiotics is a safe practice in management of persistent VUR, (otherwise healthy) children received an indwelling bladder catheter during the entire even in severe VUR. Increased awareness of parents and paediatricians for prompt procedure. diagnosis and therapy of pyelonephritis may prove to be the most important prophylactic measure in children with VUR. Results: There were 54% girls and 45% boys. Data of all patients could be traced (from medical records and microbiological reports). The mean age at the time of surgery was 6.0 ±2.4 months and the average duration for surgery was 6.4 ± 2.3 hours. Post-operatively three patients had a proven urinary tract infection by culture and two had leucocyturia in combination with bacteria or haemoglobin. The incidence of true urinary tract infections was 1.7 % and the incidence of probable infection 2.9 %.

Interpretation: There was a low incidence of urinary tract infections in infants in our study despite the presence of an indwelling bladder catheter for many hours. We conclude that otherwise healthy children do not need antibiotic prophylaxis when single bladder catheterisation is performed. 1546 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 97 COD. PP 98 The combined therapy with clarithromycine and ceftazidime of urinary An unusual case of gross hematuria tract infections caused by Pseudomonas aeuruginosa E Miorin,F Braida,I Robieux,F Colonna E Miorin(presenting author) J Zachwieja, M Zaniew, D Sobczyk, T Krynicki, A Blumczy ñski, A Siwiñska , ASS 6, P.O. S. Vito al Tagliamento, U.O. Pediatria , 33078 San Vito al Tagliamento (PN) , , Department of Pediatric Nephrology, Szpitalna 27/33 street , 60-572 Poznañ , Poland Italy Italy

Urinary tract infection (UTI) is common in pediatric practice and an important cause of A 6-year-old boy from Burkina, emigrated in Italy with his family 1 month earlier, morbidity and mortality in children. Escherichia coli remains the predominant uropathogen presented with gross hematuria and dysuria since 2 weeks. A history of recurrent dysuria (80%) isolated in acute community-acquired uncomplicated infections, followed by started in Africa, during the previous 2 months. The patient’s history disclosed that he used Staphylococcus saprophyticus (10% to 15%) and Pseudomonas aeuruginosa (PA) (9%) The to bathe in a pool of his rural village in Burkina. Physical exam was unremarkable. pathogens traditionally associated with UTI are changing many of their features, Urinalysis demonstrated hematuria (++), leukocyturia (++) and proteinuria (++). According particularly because of antimicrobial resistance. Reinfections and relapses of urinary tract to his past history of frequent baths in a Burkina pool, we examined his urine infections caused by PA are very frequent. The aim of the study was to evaluate the efficacy microscopically for the presence of Schistosoma hematobium eggs and diagnosed him as of combined treatment with clarithromycine and ceftazidime in terms of eradication of PA having urinary schistosomiasis. Ultrasonography revealed some focal areas of thickening of infection. We analyzed 20 out of 264 children with UTI in whom PA infection was the bladder wall, without other abnormalities of urinary tract. The patient was successfully confirmed with urine culture. Those children were treated for at least 14 days with the treated by oral administration of Praziquantel, (single dose 40 mg/Kg), with normalization protocol used for PA infection in patients with mucoviscidosis. Short-term eradication was of urine sediment. Infection with Schistosoma hematobium is common in several areas of achieved in all patients. Long-term study revealed relapse in 25% of infected children, all Africa, where it represents a major cause of urinary tract disease. Parasites released by with serious congenital malformations. 75% of children were treated with success. No side intermediate aquatic snail host in fresh water, enter through the skin in venous system and effects of the therapy were observed. Conclusion: The combination of clarithromycine and reach the peri-ureteral and bladder plexus. Here the adult females deposit eggs in the ceftazidime is appropriate and effective in the treatment of UTI caused by PA in children. mucosa, submucosa and muscular layer of the bladder, where they cause granulomatous This therapy was clinically efficacious, well tolerated, and cost effective, and should reaction and fibrosis, leading to urinary tract obstruction. Chronic renal failure and immune- prevent unnecessary development of antimicrobial resistance. complex-mediated glomerulonephritis may result. Since there is an increasing flux of immigrants towards Europe as well as travellers from endemic areas, it is important for European clinicians to become familiar with this traditional exotic disease.

COD. PP 99 COD. PP 100 Morphological evaluation of the renal parenchyma in children with CLINICAL FEATURES OF 76 PATIENTS WITH vesicoureteral reflux using Tc-99m MAG3 dynamic SPECT VESICOURETERAL REFLUX: STILL A MAJOR PROBLEM Masashi Morooka, Satoru Kisohara, Yasuto Yamamoto, Nihoko Ito, Yoshizo Asano O Sakallioglu, A Duzova, Y Bilginer, F Ozaltin, S Ozen, R Topaloglu, N Besbas, A Fujita Health University School of Medicine , Department of Pediatrics, , 4701192 Bakkaloglu Toyoake , Aichi Japan Hacettepe University Faculty of Medicine , Hacettepe Univ. Faculty of Medicine, Dept. of Pediatrics, Pediatric Nephrology and Rheumatology Unit , 06100 Ankara , Turkey Background: Tc-99m DMSA late static planar imaging or SPECT is being used for the investigation of renal scarring. However, this requires a waiting period of at least one hour Aim: To evaluate clinical features of vesicoureteral reflux (VUR) in a referral center in after injection, acquisition time of no less than 30 min and sedation of the patients. Diuretic Central Anatolia. Tc-99m MAG3 dynamic scintirenography has been applied in the evaluation of kidney Methods: We retrospectively investigated our medical records from 2001 to 2005. During function. 99mTc-MAG3 also provides high resolution parenchymal images some minutes this period a total of 76 patients (31 M, 45 F) were diagnosed as VUR, and are currently after injection. In this study, we investigated the feasibility of a rapid parenchymal SPECT followed in our unit. with Tc-99m MAG3 in the patients with VUR. Results: Age at diagnosis was 30.66 ± 39.34 months (range: 1-180 months); 48.7% of cases Material and methods: Twenty-five patients aged from 0.5 to 14.4 years old with congenital were less than 12-month of age. Interval from the first symptom to diagnosis was 16.04 ± VUR were entered into this study. All patients were performed both Tc-99m DMSA 27.45 months (range: 1-160 months). Chief complaint was recurrent UTI (59.2%), followed SPECT and Tc-99m MAG3 SPECT at the same period. Tc-99m MAG3 SPECT was by febrile UTI (11.8%), abdominal pain (9.2%), congenital anomalies and prenatally performed with a two-detector camera in 30 sec per revolution sequential intervals for a diagnosed pelvicalyceal ectasia (5.2%), neonatal jaundice (3.9%). On admission growth total acquisition time of 2 min, beginning immediately after an intravenous injection of a retardation was present in 7.9%, hypertension in 2.6%, and chronic renal failure in 1.3%. Of graduated dose of 20 mCi of agent. We compared the frequencies of detection for renal the 152 renal units; no reflux was detected in 21.1%, Grade I-II, Grade III and Grade IV-V scarring between these two methods. reflux was present in 36.8%, 25.0% and 17.1% respectively. VUR was bilateral in 57.9% o f Results: The frequencies of detection for renal scarring were nearly equivalent between patients. Bilateral VUR was more frequent in patients younger than 12-month of age (75% these two methods. However, there were some cases showing false-negative in Tc-99m versus 43.6%; p: 0.006). MAG3 SPECT. Most of these cases were under one year old. Complete resolution of VUR was more frequent in patients younger than 12-month of age Conclusion: Tc-99m MAG SPECT is feasible and clinically useful for evaluation of renal (70.4% versus 39.1%; p: 0.030). Renal scar was more common in Grade IV-V compared to cortical damage in the patients with VUR, especially over than one year old. Grade I-III; both on admission (63.6% versus 31.5%; p: 0.044) and during the follow-up (76.9% versus 37.3%; p: 0.009). Teflon injection was performed in 3 (3.9%), and ureteroneocystostomy was done in 9 (11.8%) patients. Two patients, with delayed diagnosis (14 year of age and 17 year of age), end-up with end-stage renal failure. Conclusion: Early diagnosis and proper management of VUR result in favorable outcome. Higher grade, older age at diagnosis and delay in diagnosis are poor prognostic factors. Pediatr Nephrol (2006) 21:1493–1635 1547

COD. PP 101 COD. PP 102 Long Term Prognosis Of Upper Urin ary Tract Infections In Children: PROTHROMBOTIC RISK FACTORS IN PATIENTS WITH A Systematic Review. RECURRENT TROMBOSIS OF THE ARTERIOVENOUS FISTULA A Toffolo1, D Gobber2, A Calderan2, G Zacchello2, G Montini2 1 Pediatric Dertement, B Tavil*, A Bakkaloglu**, and A Gurgey* *Hacettepe University Faculty of Medicine, Ospedale di Oderzo (TV), 2 Pediatric Departement, Padova, Italy Ihsan Dogramac› Children’s Hospital, Pediatric Hematology Unit Ankara-TURKEY Nephrology Dialysis and Transplant Unit , Pediatric Departement , 35128 Padova , Italy **Hacettepe University Faculty of Medicine, Ihsan Dogramac› Children’s Hospital, Pediatric Nephrology Unit Ankara-TURKEY It is commonly reported that upper urinary tract infections (UTI) have a large potential to , Hacettepe University Faculty of Medicine Ihsan dogramac› children`s Hospital Pediatric produce long-term morbidity, especially renal failure, hypertension and pregnancy Hematology Unit 06100-S›hh›ye , 06100 Ankara , Turkey complications. We sistematically reviewed the literature in order to evaluate the long term complications of Atreio-venous (A-V) fistula thrombosis is a common and expensive complication. In this pediatric UTI per se. Articles were obtained from the MEDLINE (1980-2006) and study, we aimed to investigate the role of prothrombotic risk factors in the development of EMBASE (1985-2005) database, using a search strategy to identify cohort studies which recurrent A-V fistula thrombosis. Between January 1998 and June 2005, 11 patients with comprised subjects with a UTI during childhood and which considered the following long recurrent thrombosis of A-V fistula were refered to Hacettepe University Faculty of term outcomes: renal failure, hypertension, growth, pregnancy complications. The titles and Medicine, Pediatric Hematology Units for evaluation of thrombosis. The subject of this abstracts resulting from these searches were used to identify papers definitely or potentially study is the 11 chronic renal failure patients with recurrent A-V fistula thrombosis. The useful, through an in-out form. These articles were reproduced in full to extract data of prothrombotic risk factors were studied for all of the patients. Of these 11 patients, 6 interest using a specific extraction form. The quality of each article was rated by using the patients (mean age,14.8±2.6 years) were children and 5 (mean age, 37.6±16.6 years) were Newcastle-Ottawa quality assessment scale cohort study. adults. All patients had at least two episodes and 31 total episodes of thrombosis in the A-V 24 articles were finally identified for the following outcomes: 1) Deterioration of renal fistula (mean: 2.8±1.3 episodes, range: 2-6 episodes) were observed. Eight of 11 patients function in 0-56% of 15 cohorts (1678 patients); 2) Hypertension in 0-35% of 15 cohorts (72.7%) had at least one prothrombotic risk factors. Two patients (18.2%) had FV G1691A (1466 patients); 3) Pregnancy: 5 cohorts of 282 pregnancies (no relevant problems for the and two (18.2%) had prothrombin G20210A mutations. These mutations are more common fetus); 4) Body growth: 6 cohorts of 665 patients (a modest transitory negative effect was in the patients with recurrent A-V fistula thrombosis than normal Turkish population present in children with UTI and reflux). The quality of the articles is highly variable; there (18.2% versus 7.1% for FV G1691A and 18.2% versus 2.2% for Prothrombin G20210A is a great eterogeneity as far as inclusion criteria of the patients, follow-up and evaluation of mutation) (p<0.05). the outcome. From the data of the literature it is not possible to draw a unique conclusion on In conclusion, recurrent A-V fistula thrombosis should be considered as the other types of the long term consequences of UTI per se. recurrent thrombosis and hereditary prothrombotic risk factors should be investigated to detect the prothrombotic tendency of the patients in countries where these hereditary risk factors are common.

COD. PP 103 COD. PP 104 Procalcitonin serum levels in children undergoing chronic hemodialysis THROMBOLYTIC THERAPY IN HEMODIALYSIS CHILDREN F Lorton, F Veinberg, G Deschênes, A Bensman, T Ulinski WITH VASCULAR ACCESS THROMBOSIS Hôpital Trousseau , Department of Pediatric Nephrology , 75012 Paris , France S V Baiko, A V Soukalo Republican Center for Pediatric Nephrology and Dialysis, Minsk,Belarus Infections account for considerable morbidity and mortality in patients requiring - , Republican Center for Pediatric Nephrology and Dialysis , 220018 Minsk , - Belarus hemodialysis (HD). Procalcitonin (PCT) – a low molecular weight protein of 13 kDa- helps to distinguish viral from bacterial infections and to evaluate the severity of bacterial We had 11 cases of vascular access thrombosis, which occurred in 4 children on infections. We investigated 1/ PCT baseline levels in eight children undergoing chronic HD hemodialysis at the Republican Center for Pediatric Nephrology and Hemodialysis within 2 with high flux membranes, 2/ changes in the serum levels of PCT, CRP and beta2- last years. Thrombosis was caused by hypotension in 5 cases, poor fistula care by patients in microglobulin (a peptide with similar molecular weight as PCT) before and after 4-h 4 cases. The reason was not known in 2 cases. hemodialysis sessions in eight children on chronic HD. PCT was measured in three mid- In all cases the children were admitted to the hospital within the first 6 hours (2.86±1.56 week sessions for each patient. In seven uninfected children serum PCT was increased (0.75 hours, on the average) from fistula blood flows obstruction. Thrombolysis with ± 0.07 ng/ml), whereas CRP levels were normal. PCT post dialysis decreased significantly streptokinase (standard scheme) was performed in all cases. Blood flow restored 4-19.5 by 40% (p<0.001) compared to initial values, whereas CRP levels pre and post HD were not hours (8,73±5.02 hours, on the average) following streptokinase infusion termination in 10 different. Beta2-microglobulin decreased by 70% probably due to its different biochemical cases and 72 hours after the procedure in 1 case. The duration of thrombolysis was 10-24 characteristics. PCT serum levels 15 and 60 minutes after the HD session remained hours (16.09±4.9 hours, on the average). unchanged compared to those at the end of the HD session, suggesting renal failure with Complications of thrombolysis were as follows: nausea, vomiting and weakness in 2 cases; accumulation between HD sessions, rather than HD induced production to be responsible flush and lacrimation in 1 case. Reduced speed of infusion relieved the symptoms. for the increased baseline PCT serum levels. Conclusion: CRP serum levels are not affected Thrombolytic therapy of vascular access thrombosis in hemodialysis children is a highly by HD in our cohort. Moderately elevated baseline PCT serum levels and dialysability of efficient and safe method of treatment with the blood flow restored in 100% of cases in PCT should be taken into consideration. However, increase of serum PCT in patients with early admission to hospital. severe bacterial infections is generally massive (10 to 1000-fold), suggesting a low risk for false negative results in such cases. 1548 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 105 COD. PP 106 Blood Volume Monitoring in Pediatric Hemodialysis: Diagnostic Value? The Response of Asymmetric Dimethylarginine to the Hemodialysis- DK Hothi (presenting author) E Harvey D Geary Associated Hypotension in Patients with End-Stage Renal Disease Hospital for Sick Children , 555 University Avenue , M5G 1X8 Toronto , Ontario Canada E.Sulyok, B. Csiky, J. M. Lobenhoffer, S. M. Bode-Böge r Institute of Health Promotion and Family Care Faculty of Health Sciences , Vörösmarty u. Introduction: Current pediatric data reports a correlation between reduced relative blood 4. , 7621 Pécs , Baranya Hungary volume (RBV) and occurrence of adverse intradialytic events. Objectives: To determine whether the temporal changes in RBV were diagnostic o f Abstract treatment failure; and to determine what characteristics of the RBV curve best correlated with a poor outcome. The present study was undertaken to define the role of asymmetric dimethylarginine Method: Blood Volume Monitoring (BVM) using the Fresenius® module is routinely (ADMA) in the control of blood pressure during hemodialysis (HD) by comparing l- performed in our unit. Sodium and ultrafiltration profiles and mannitol infusions are arginine, ADMA and symmetric dimethylarginine (SDMA) levels in patients with (18 individually prescribed. 74 BVM records from 11 chronic patients were retrospectively patients) or without (13 patients) hypotensive episodes during HD sessions. reviewed to compare RBV with heart rate and blood pressure during successful (n= 26) and The clinical variables, the routine laboratory parameters and the underlying pathologies of failed (n=48) treatments. Treatment failure was defined as hypotension and/or intradialytic end-stage renal disease (ESRD) were comparable in the two groups. Blood pressure was symptoms. serially recorded and plasma l-arginine, ADMA and SDMA levels were measured before Results: The association between the occurrence of intradialytic events and absolute level of and after HD-treatment by using liquid chromatography-mass spectrometry method. RBV or change in systolic and diastolic BP was statistically insignificant. Change in heart It was demonstrated that in patients with ESRD on maintenance HD plasma rate was significantly associated with treatment failure (OR 1.05, p=0.05). dimethylarginines were markedly elevated and they responded to HD with a significant fall Using receiver operator characteristics (ROC) analysis the absolute RBV value was a better by the end of the sessions. ADMA levels in patients having hypotensive episodes during discriminator of outcome than hourly RBV change. Based on published RBV thresholds of HD were significantly higher than in those maintaining their blood pressure at predialysis 92% at the end of the 1st hour, 88% end of 2nd and 84% end of 3rd, we estimated an 80%, levels. 84%, 83% specificity and 52% ,61%, 47% sensitivity for treatment failure respectively. 4th Furthermore, there was a significant inverse relationship of the minimum systolic and hour and final RBV values were poor discriminators of outcome. diastolic blood pressure during HD to the pre-and postdialysis ADMA levels. Conclusion: Levels of RBV were poor predictors of the occurrence of intradialytic events. It is suggested that excessive NO generation is involved in the HD-associated hypotension RBV thresholds have a good specificity but poor sensitivity for discriminating between and induces an increase in plasma ADMA levels to prevent the further fall in bloo d successful and failed treatments. pressure.

COD. PP 107 COD. PP 108 ARE PERMANENT CATHETERS A SA FE VASCULARACCESS IN ULTRASONOGRAPHY PREOPERATIVE MAPPING OF BLOOD CHRONICALLY HEMODIALYZED CHILDREN ? VESSELS BEFORE ARTERIOVENOUS FISTULA K Zachwieja 1, M Miklaszewska 1, D Droýdý 1 , J A Pietrzyk 1, W Król –Jawieñ 2 , A Kral CONSTRUCTION IN PEDIATRIC PATIENTS WITH END-STAGE 3 Dialysis Unit 1, Dept. of Pediatric Cardiology 2, Dept. of Pediatric Cardiac Surgery 3, RENAL DISEASE University Children`s Hospital of Cracow, Poland J Buturoviã, R Rus, and R Ponikvar Dialysis Unit, University Children`s Hospital of Cracow , ul. Wielicka 265 , 30 - 663 , Department of Nephrology, University Medical Center , 1000 Ljubljana , Slovenia Kraków , Poland Background. Ultrasonography preoperative mapping of vessels before arteriovenous (AV) The paper’s aim is to analyze the complications related to permanent catheters used as a fistula conctruction is well established practice in adult end-stage renal disease (ESRD) vascular access in chronically hemodialyzed (HD) children. In 1998 to 2005 34 permanent patients. The aim of retrospective study is to report our experience with this approach in catheters surgically implanted were used as a vascular access for HD in 21 patients in pediatric patients. average age 13,6 yrs (range 5-26 yrs). The catheters were placed mainly into right internal Methods. From 2000-2005 preoperative ultrasonography examinations before AV fistula jugular vein. Average patient’s observation time was 17 (range 3 to 73) months and average construction were performed in 12 children with ESRD, 6 boys and 6 girls, aged 15,8±3,1 catheter’s usage time was 10,6 (range 0,5-40) months. No complications were observed years (11-21). Both arms and forearms were examined, using linear 7 Mhz probe and only in 2 patients with short time of observation (< 6 months). Complication frequency rate ultrasonography monitor Siemens Acuson Sequoia. Optimal position for AV anastomosis was 0,7 episode/observation month (range 0,0-5,0), the thrombotic complications rate was was suggested. If vessels were not optimal, 8-weeks handgrip training was prescribed 0,3 and infectious complications index was 0,2 episode/month. Rare mechanical before the operation. AV fistula was constructed by trained nephrologist, under local o r disfunctions were seen in 2 patients (the catheter rupture and falling out). Serious general anesthesia. thrombotic complications were noted in 2 cases (carotic veins bilateral severe stenosis with Results. Suitable veins on the right forearm were recorded in all but one patient, with marked collateral circulation accompanied and extensive thrombosis of the femoral and internal diameter of (under the compression) 3.2±0.4 mm (3.0-3.5). On the left side suitable iliac veins). Diagnostic and therapeutic angiographic investigation of carotic venous system veins were also found in all but one patient, measuring 3.3±0.3 mm (2.9-3.5). Right radial and catheter placement were performed in 2 patients. Among 34 analyzed catheters – internal diameter was 1.8±0.3 mm (1.4-2.1), left 1.8±0.25 mm (1,2-2,1), right radial artery function of 11 (32%) was normal, 13 (38%) were exchanged, 5 (15%) were surgically peak systolic velocity was 25±4 cm/s (23-30), and left 24±5 cm/s (17-32), respectively. In replaced, in 6 cases catheters were removed with of the vascular access or dialysis method. all but one patient AV fistula was successfully constructed and developed for use. The Conclusions: Use of permanent catheter as chronically vascular access for HD in children is patient with unsuccessful AV fistula construction was receiving steroids and had suboptimal associated with high complications rate. This type of vascular access should be considered vessels. in the last resort when creation of the other vascular access is unlikely. Conclusion. Ultrasonography can successfully assess arteries and veins of arms and forearms in pediatric ESRD patients, suggest the optimal position for AV anastomosis and the need for preoperative handgrip training, thus enabling good AV fistula function in the majority of patients. Pediatr Nephrol (2006) 21:1493–1635 1549

COD. PP 109 COD. PP 110 SEVERE BILATERAL JUGULAR VEINS STENOSIS BEING A OXALATE KINETICS IN AN INFANT WITH SYSTEMIC RESULT OF PERMANENT CATHETERIZATION IN OXALOSIS ON CHRONIC HEMODIALYSIS CHRONICALLY HEMODI ALYZED PATIENT – CASE REPORT E Mancini1, M Petrarulo2, S Picca1(presenting author). 1Dept. of Nephrology and Urology, K Zachwieja 1, D Droýdý 1, M Miklaszewska 1, J A Pietrzyk 1, W Król – Jawie ñ 2, A Kral Dialysis Unit, “Bambino Gesù” Children’s Research Hospital, Rome. Italy. 2Nephrology 3, P Weryñski 3. 1 Dialysis Unit1, 2 Dept. of Pediatric Cardiology, 3 Dept. of Pediatric Unit, Renal Stone Laboratory, “Mauriziano Umberto I” Hospital, Turin.Italy. Cardiac Surgery University Children`s Hospital of Cracow, Poland , Dept. of Nephrology. P.zza S. Onofrio, 4 , 00165 Rome , Italy Dialysis Unit, University Children`s Hospital of Cracow , ul. Wielicka 265 , 30 - 663 Kraków , Poland No form of dialysis is generally considered able to remove sufficient amounts of oxalate (Ox) in patients with systemic oxalosis (SO) awaiting for liver-kidney transplantation (LK- Permanent venous catheters are considered as efficient vascular access in chronically Tx). We report on an infant with SO treated with chronic hemodialysis (HD) from four to hemodialyzed children. The aim of the paper is to present some complications related to six eighteen months of age. year period of permanent catheterization. In 14 year old boy having been hemodialyzed A 4.5 kg, four-month-old girl presented with primary hyperoxaluria type 1 and SO, since 1995 - permanent catheter had been surgically implanted into right internal jugular nephrocalcinosis, anuria, one fine radiodense line in the growth plate of long bones, initial vein. In 2001 due to recurrent bacteriemias catheter was removed and new one was inserted flecked retinopathy. She was treated with daily hemodialysis (5-7 hours per session) with a into left internal jugular vein. Repeated catheter malfunction episodes have been observed CRRT monitor until the age 10 months and afterward with an hemodialysis monitor until despite fibrynolytic therapy. In 2004 dilatation of superficial jugular veins was noted. The the present age of 18 months. PreHD plasma Ox ranged 162-211 mmol/l, indicating Doppler ultrasound and angiographic examination of carotic vessels revealed bilateral turbulent Ox generation (GOx). GOx was calculated from linear increase over interdialytic severe stenosis of the internal and common carotic veins and right subclavian vein with time (Marangella, 1992) and Ox mass removal (MROx) from Ox concentration in the marked collateral circulation accompanied. Balloon dilatation of right jugular angle was dialysate. Both with CRRT and with hemodialysis monitor, Ox balance (BOx) was always carried out. The catheter tip was surgically relocated. In 2005 the catheter dysfunction was slightly negative (GOx=540-855, MROx= 612-1048 mmol/day; BOx –19/–75mmol/day). noted again. In subsequent angiographic investigation - suspicion of catheter in-growth into Growth (presently, 25°centile for height and 30° for weight) and neuromotor development vascular wall was raised. The patient was switched to peritoneal dialysis after inefficient were normal. Ocular findings remained unaltered. With growth, radiodense line moved as a creations of the arterio-venous fistulas (three efforts). The permanent catheter was safely radiolucent band in the metaphyses of all long bones and remained isolated. Patient is removed. As a definitive therapy - patient received living donor kidney transplantation presently in a waiting list for LK-Tx. however the carotic collateral circulation is still present without any clinical symptoms. Conclusions: 1) differently from older patients, negative Ox balance is possible with Conclusions: 1. Jugular veins monitoring with Doppler ultrasound should be recommended intensive hemodialysis in infants with SO and high GOx. 2) this is probably due to infants’ method in patients chronically dialyzed with permanent catheters 2. Angiographic small volume. 3) in our patient, the favorable clinical course seems to confirm calculated examination is a safe and efficient method in diagnosing catheter’s dysfunction. 3. Ox kinetics. Cooperation with the cardiologic team who perform angiographic study may improve outcome of dialyzed children.

COD. PP 111 COD. PP 112 HEMOPERFUSION IN POISONINGS: EXPERIENCE IN 26 USEFULNESS OF PERMANENT CATHETERS IN PEDIATRIC CHILDREN DIALYSIS – ONE CENTRE EXPERIENCE B Mutlu1, K Bek2, O Özkaya2, A Da ðdemir3, K Baysal4 1 Ondokuz May›s University, T Zimoñ, T Jarmoliñski, S Paradowski* Department of Nephrology and Dialysis and Department of Pediatrics, Samsun, TURKEY 2 Ondokuz May›s University, Department of Department of Pediatric Surgery, District Children`s Hospital, Szczecin, Poland, e-mail: Pediatric Nephrology, Samsun, TURKEY 3 Ondokuz May ›s University, Department of [email protected] Pediatric Oncology, Samsun, TURKEY 4 Ondokuz May ›s University, Department of Dept. of Nephrology and Dialysis, District Children`s Hospital , Úw. Wojciecha 7 , 70-410 Pediatric Cardiology, Samsun, TURKEY Szczecin , Poland Ondokuz May›s University Faculty of Medicine , Pediatric Nephrology , 55139 Samsun , Turkey The aim of our study was to present own experience with using permanent central venous catheters (PC) as vascular access in pediatric hemodialysis. Indications to PC placement, Accidental or intentional drug overdose is a frequent cause of hospital admission in time of dialysis with PC and complications were analyzed. Between 2001 and 2005 eight children. In severe cases hemoperfusion(HP) may be required for drug removal. Here we PC were implanted into subclavian veins of 7 children. The procedure was performed under report our HP experience in 26 intoxication cases followed between january 2000 and may general anesthesia and guided by rentgenoscopy. Two kinds of catheters: GamCath 2005 in our institution. Male to female ratio was 6/20 with an age range of 1,5-16 years (Gambro) and Hemo-Cath (Medcomp) were placed and the PC diameter was 8-12F. PC (Mean: 5,7). Sixteen cases were secondary to accidental ingestion and 10 to suicidal served as long-term vascular access in children with no conditions to create arterio-venous attempts. The interval between ingesting the drug and applying to emergency service ranged shunt in 5 cases and as temporal access during preparation to living related donor kidney between 2 to 24 hours. In 21 of the patients ingested drugs were amytriptyline (16), valproic transplantation (2) or during maturation of natural shunt (1). PCs were heparinized every acid (1), haloperidol (1), mesoridazine mesylate (1) and multiple drugs (2) with mainly 24-48hr with the solution of 1000-5000U/ml of unfractionated heparin. After dialysis all neurologic actions. Others were organic phosphorus in 3, carbon monoxide in 1 and children were sent home. Mean time of PC using was 4,2+2,4 mo (1,5-8,0mo). Four mushroom poisoning in 1 patient. Active charcoal and gastric lawage had been applied to catheters were removed electively, 2 were damaged by patients, 1 patient died with all cases. Neurologic and cardiac findings were the main indications for HP. After HP functioning PC and 1 PC is still working. In all children blood flow adequate for effective dramatic resolution in neurologic and cardiac findings was achieved in all patients. Only dialysis was achieved. Beside mechanical PC destruction, performed at home by two one patient developed neurological sequela due to prolonged hypoxia. All patients were children deprived sufficient parent’s supervision, no complications were observed. discharged after a mean hospital stay of 7 days (range:1-67 days). Conclussion: PC provides comfortable, safe and long-lasting vascular access in In conclusion HP seems a very effective life saving treatment modality in children with hemodialysed children without arterio-venous shunt. severe poisonings. Prompt and systematic clinical evaluation of such children is of paramount importance. In the case of failure or inefficiency of conventional supportive interventions HP may be considered as the last choice for the specific drug or the substance even if controversial. 1550 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 113 COD. PP 114 VASCULARACCESS IN PEDIATRIC CHRONIC HEMODIALYSIS Circulating Endothelial Cells as a Marker of Vascular Endothelium PATIENTS – SLOVENIAN EXPERIENCE Status in Children Under Regular Hemodialysis Therapy R Rus J Buturovic Ponikvar (Presenting Author) R Ponikvar M S Faheem, H M Afifi*, S S El-Sayed, A H Hamed Departments of Pediatrics and University Clinical Centre Ljulbjana, Division of Pediatrics, Department of Nephrology , Clinical Pathology*, Faculty of Medicine, Ain Shams University, Cairo, Egypt Stare pravde 4 , 1000 Ljubljana , Slovenia Faculty of Medicine, Ain Shams University , 16 Mahmoud Elbadri, 8th Area, Nasr City , 11471 Cairo , Egypt Background. The aim of our report was to present our experience with vascular access in chronic pediatric hemodialysis patients. Accelerated atherosclerosis is a major cause of morbidity and mortality in patients under regular hemodialysis (HD). Our aim was to measure circulating endothelial cells (CECs)as Patients and methods. 32 children, 12 males and 20 females, aged 13.8±3.4 years (6.3 to a marker of vascular endothelium status in children under regular HD. 19.7), with end-stage renal failure started hemodialysis from 1979 to 2005 at University This study was conducted on 30 children on regular HD as group I with mean of age Medical Center Ljubljana, as their first form of renal replacement therapy. 15±2.3y and of HD 4 ± 2.7y. Group II of 30 age and sex matched healthy children was also included . Results. Native arteriovenous fistulas (AVF) were used at the start of hemodialysis in 9/32 All children were evaluated clinically and laboratory by CBC and profiles for renal (28.1%) and central venous catheters in 23/32 children (71,8%). AVF were later used in function, calcium-phosphorus homeostasis, lipids and iron-ferritin status. High-sensitivity 75% of children on hemodialysis. If construction of AVF was not successful or possible, CRP by ELISA and CECs by flowcytometry using anti-CD146 were also tested. CECs was central venous hemodialysis catheter was used in single-needle dialysis mode. If estimated pre-dialysis and post-dialysis in group I. malfunction occured, the catheter was replaced using guide-wire. All together 44 AVF We found significantly higher pre-dialysis and post-dialysis counts of CECs as compared to operations (constructions or reconstructions) were performed in 32 children, 27/44 (61.4%) controls. The post-dialysis count was significantly higher than the pre-dialysis one. Serum of operations were on left forearm, 14/44 (31.8%) on right forearm and the rest in cubital high-sensitivity CRP was significantly higher in group I than group II. fossa. The primary failure rate was 20.5% (9/44). 18/32 (56.3%) patients received cadaveric Both of the age of the patient and the duration of illness had significantly positive or living related kidney graft after 3.8±4.5 years (3 months to 18.5 years), 4 started correlation with CECs count. TG, serum cholesterol, HDL-c, LDL-c and risk ratio (HDL- peritoneal dialysis after 5 to 15 years, 2 reached partial remission after 8 months, 8 patients c/LDL-c) collectively had a significant direct positive effect on CECs. Similar finding was are still on hemodialysis (from 1 to 14 years) and one girl died after being unsuccessfully found on addition of SBP and DBP to these factors. A similar effect was obtained when S. transplanted and returned to hemodialysis. Ca2+, S. phosphorus, CaxP and iPTH were add together. We could conclude that number of CECs might reflect the state of vascular endothelium and Conclusion. Native forearm arteriovenous fistula was the most frequent vascular access considered a surrogate biological marker for vascular and cumulative cardiovascular risk in used in our pediatric chronic hemodialysis patients. The alternative vascular access was children on HD therapy. hemodialysis catheter. The majority of patients later received cadaveric or living related kidney graft.

COD. PP 115 COD. PP 116 Continuous Renal Replacement Therapy-First Experiences Five years experience with extracorporeal techniques in paediatric N Stajic, J Putnik, A Licanski, R Bogdanovic Institute for Mother and Child Health Care, intensive care (PICU) Belgrade I Shaheen B Harvey A Mayer D Thomas A Watson Institute for Mother and Child Health Care , Radoja Dakica 6 , 11070 Belgrade , Serbia Nottingham University Hospitals , Children & Young People`s Kidney Unit, City Hospital Serbia & Montenegro Campus , NG5 1PB Nottingham , UK

Continuous renal replacement therapy (CRRT) is used for the treatment of the acutely ill Background and Methods patients. Continuous veno-venous haemofiltration (CVVH) and plasmafiltration (PF) are employed We describe 12 patients treated in the Intensive care unit during the first year after the in PICUs but the indications have not been clearly defined and the techniques require method had been established. Prisma Hospal CRRT machine and polyacrylonitrile expertise and training. We reviewed the use of CVVH and PF in 2 regional PICUs (~900 hemofilters AN 69 were used. The pre-filter replacement fluid and dyalisate were annual admissions) between January 2000 and December 2004. bicarbonate buffered. A femoral vein dual-lumen hemodialysis catheter was the preferred method of access in patients whose weight was above 10 kg and two one - lumen (jugular Results and femoral vein) catheters in others. Anticoagulation was performed in all patients by 90 children (48 male) were treated with a median age of 36 months (range 1 day – 17yrs) heparin infusion. Circuits were primed with albumin in all circulatory unstable patients and and median weight of 15kg (range 1.8-80kg). This represents approximately 2% of the total others whose weight was under 5 kg. admissions to the 2 PICUs over the 5 year period. 36 patients (40%) were <2 years, 17 Seven of 12 patients were male and five female.The average age was 49 months (range 0,5- patients (19%) 2-5 years, 37 (41%) >5 years of age. 74 patients (82%) received CVVH 141 months) and their weight ranged from 3,2 to 88 kilograms. Indications for the CRRT alone while 13 (14%) received PF and CVVH; 3 PF alone. Sepsis was the indication in 54 were congenital metabolic disorder in two patients, intoxication in one, hemolytic uremic patients (60%) with acute renal failure in 18 patients (20%), metabolic conditions in 7 syndrome in two, congenital nephrotic syndrome in one patient, congenital bilateral stenosis patients (8%). PF prior to CVVH was used in 9/28 patients with meningococcal sepsis and of pyeloureteric junction in one, multiple organ dysfunction syndrome (MODS) in four and 4/12 renal patients. Overall survival was 53/90 patients (59%) with survival rates of 33% v acute glomerulonephritis in one patient. Minimal CRRT time was 13 hours, maximal 912 71% in oncology patients and meningococcal sepsis respectively (p=0.008). Survival in hours. In 7 patients CVVHDF was performed, in three CVVHD and CVVH in one patient. primary renal patients was 92%. There was no difference in survival in those ventilated or Nine patients survived to leave the ICU. Three patients died, two with MODS and the third receiving inotropic support. with congenital nephrotic syndrome who died from sepsis. Continous renal replacement therapy is very useful method for the treatment of acute renal Conclusions insufficiency, multiorgan failure, intoxication and congenital metabolic disorders. This study confirms the relatively low usage of CVVH and PF in 2 general PICUs not treating cardiac or liver failure patients. The age and weight range of the patients pose particular technical difficulties and the intermittent demand requires constant updating of staff expertise. Objective clinical markers for commencing CVVH alone or in combination with PF remain to be defined, especially in high risk groups. Pediatr Nephrol (2006) 21:1493–1635 1551

COD. PP 117 COD. PP 118 Hemolytic Uremic Syndrome and Verocytotoxin (VT)-producing E.coli Acute glomerulonephritis and subacute infective endocarditis in (VTEC) infection in Italy children A Caprioli, M Brigotti, M Ciofi, T De Palo, A Edefonti, F Emma, AVS Ferretti, M Gaido, J Exantus1, M Cean, P Raymond, D Azor, R.Duret3, R. Pilie4 1, 2. Pediatric Emergency, A Gianviti, G Pavone, I Ratsch, M Salata, G Scavia, A E Tozzi, E Verrina and C Pecoraro Hôpital de l’Université d’Etat d’Ha¿ti (HUEH); 3. Echography Unit, Centre Medical du Registry of Hemolytic Uremic Syndrome of the Italian Society of Pediatric Nephrology Champ de Mars; 4. Echocardiography Unit, Polyclinique De l’avenue Lamartiniere Santobono Children`s Hospital , Department of NephroUrology, via Mario Fiore n°6 , , Centre Medical, 21-27 Chemin des Dalles , HT6110 Port-au-Prince , Haiti 80129 Naples , Italy Acute glomerulonephritis is a rare complication of acute or sub acute infective endocarditis Verocytotoxin (VT)-producing E.coli (VTEC) infection represents the main cause o f in children, owing to deposit of immune complex into renal parenchyma. Hemolytic Uremic Syndrome (HUS) in children. A nationwide surveillance system of HUS We report the case of a male adolescent of 14 years old admitted for subacute infective was introduced in Italy in May 1988 to follow the trend of VTEC infections. endocarditis and cardiac insufficiency. The transthoracic echocardiography showed aortic For each patient, epidemiological and clinical information was collected by a standardized and mitral insufficiency and no vegetations, valvulopathy of probably rhumastimal origin. questionnaire. Laboratory diagnosis of VTEC infection was based on the detection of He was on PNC crystalline, amino glycoside and diuretic for ankle edema. On day six, he VTEC and free VT in stools and of antibodies to the lipopolysaccharide (LPS) of presented anuria without hypovolemia, no diastolic pressure. Plasma creatinine was 4.5 serogroups, O26, O103, O111, O145, and O157 in the sera. The immuno-detection of VT mg/dL then 9 mg/dL; On urinalysis, we found hematuria, renal cells and proteinuria. The on circulating neutrophils was also performed on some patients. renal ultra sonogram detected nephritis, increased vascular resistance and loss of diastolic As of December 2005, 481 cases have been notified, accounting for a mean annual flux. Dopamine and fluid restriction were added at the medication; antibiotics were given at incidence of 0.31 x100,000 in the 0-14 age group with a significant difference among the renal failure regimen. He had a progressive recovery of the renal function without regions (from 0.15 to 1.1); median age of patients: 23 months, 53% males. Most cases hemodialysis. Now he has 0.7 mg/dL of creatinine and he is waiting for cardiac valve (53%) occured in summer from june to september. Seventy-nine per cent of the cases had surgery. prodromal symptoms such as bloody diarrhea (26%) and non-bloody diarrhea (51%). Five patients (1.0%) died from the disease. Stools and/or sera were collected from 380 cases. Evidence of VTEC infection was observed in 255 cases (67%). The VTEC serogroups most commonly detected were O157 (37% of the VTEC-positive patients), followed by O26, O145, O111 and O103. The number of cases associated with non-O157 infections increase d over time: from 1997 the O26-associated cases are the most frequent. During the surveillance-period 4 epidemic clusters have been registered: 1992-Lombardia, 1995- Veneto, 1997 and 2005 Campania.

COD. PP 119 COD. PP 120 Comparison between serum cystatin C and creatinine in the immediate Childhood acute renal failure: 22 years experience in a university follow-up of pediatric renal transplant recipients hospital in Southern Thailand W F Tromp, M Kool, G Offner, N Özden, A Bökenkamp P Vachvanichsanong, P Dissaneewate, A Lim, E McNeil VU medical center , de Boelelaan 1117 , 1081 HV Amsterdam , The Netherlands Department of Pediatrics, Faculty of Medicine , Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, Hat Yai, 90110, THAILAND , 90110 Hat Yai , Background: Serum cystatin C (Cys) has been shown to be superior to creatinine (Crea) for Songkhla Thailand the detection of mild renal dysfunction in many cross-sectional studies. Recent data in adults suggest that Cys detects incipient renal failure one day earlier than Crea. BACKGROUND: Acute renal failure (ARF) is not common in general clinical practice but Aim: To compare Cys and Crea in the early follow-up after pediatric renal transplantation. is not an uncommon cause of morbidity and mortality in tertiary referral centers. Patients and Methods: Retrospective chart review of the early post-transplant period in 22 OBJECTIVES: The objectives of this study were to review the prevalence, etiology, patients (13m/9f; age 10.7±5.1 years) in whom 33.5±8.2 simultaneous daily measurements morbidity and mortality of ARF in a large tertiary institution in southern Thailand, to of Crea (enzymatic assay) and Cys (immunoturbidimetric assay) had been documented. examine any differences in ARF cases diagnosed over a 22-year period, and to determine Daily assessment for a critical rise in marker concentration defined as an increase by more the risk factors indicating mortality. than 2SD of the three preceding measurements. Comparison of the kinetics of Cys and Crea PATIENTS AND METHODS: The case records of children aged from one month to 17 during prolonged episodes of transplant dysfunction by calculating the time until analyte years diagnosed with ARF from February 1982 to December 2004 in the Department of concentration increased by +2SD, +4SD, +8SD and +16SD above baseline. Pediatrics, Songklanagarind Hospital, southern Thailand were reviewed. Results: On average, a critical rise in Cys was observed on 5.36±2.6 days compared to RESULTS: A total of 311 children with 318 episodes of ARF were included, 177 boys 5.91±3.13 with Crea (ns). In total, 33 episodes of prolonged transplant dysfunction were (55.7%) and 141 girls (44.3%), aged 1 month-16.7 years (mean 7.6 + 5.1 years, median 7.8 observed in 12 children. The +2SD criterion was met after 1.32±0.89 (Cys) vs. 1.43±0.81 years). The etiologies of ARF in each age group were significantly different (p < 0.001). days (Crea), +4SD after 1.94±1.7 vs. 2.0±1.22, +8SD 2.54±2.44 vs. 2.5±1.4, +16SD Overall, sepsis was the major cause of ARF, accounting for 68 episodes (21.4%), followed 3.25±1.9 vs. 4.75±5.5 (all not significant). There was a high degree of agreement between by hypovolemia, post-streptococcal glomerulonephritis (PSAGN), systemic lupus Cys and Crea in the detection of transplant dysfunction (kappa for the +2SD criterion erythematosus (SLE) and infectious diseases (ID). Renal replacement therapy (RRT) was 0.80±0.11, +4SD 0.69±0.12, +8SD 0.69±0.13, +16SD 0.84±0.11). performed in 55 cases (17.3%). The overall mortality was 41.5%. Logistic regression Conclusion: In this pediatric population, Cys and Crea performed comparably in the analysis showed disease groups and creatinine levels were significant independent detection of early renal transplant dysfunction. predictors for outcome. CONCLUSION: The incidence of ARF in Songklanagarind Hospital was 0.5-9.9/ 1,000 pediatric patients with a mortality rate of 41.5%. Sepsis was a major cause of ARF and mortality. Etiologies of ARF and serum creatinine level were significant independent predictors of mortality. 1552 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 121 COD. PP 122 PROGNOSTIC FACTORS IN AC UTE RENAL FAILURE IN Atypical/Recurrent Haemolytic Uraemic Syndrome: Patients without ASPHYXIATED NEWBORN the Factor H related protein 1 (FHR1) V Vusurovic J Mitrovic N Antonijevic-Jeftenic F. Prüfer1, S. Martini2, J. Scheiring1, V. Mair1, M. Griebel2, S. Fründ3 , M. Bulla3,T. University children`s hospital , Tirsova 10, Neonatal unit , 11000 Belgrade , Serbia Serbia Knüppel4, B. Tönshoff4 , J. Drube5 , G. Offner5 , M. Kirschfink6 , S. Heinen7, P. Zipfel7, & Montenegro R Würzner8, L.B. Zimmerhackl1 1Department of Pediatric University Innsbruck, 2Department of Pediatric University München Schwabing, 3Department of Pediatric Introduction: The most common causes of acute renal failure (ARF) in perinatal University Münster, 4Department of Pediatric University Heidelberg, 5Department of asphyxiated newborns (PAN) is systemic hypotension (prerenal ARF), cortico, tubular and Pediatric University Hannover, 6UK Heidelberg, 7HKI Jena, 8Department of Hygiene, medullary necrosis (renal ARF). It may bee oliguric and nonoliguric. Microbiology and Social Medicine Innsbruck Aim: This study was conducted to evaluate importance of renal indices in prognosis and Univ.-Klinik für Kinder- und Jugendheilkunde , Anichstraße 35 , 6020 Innsbruck , Austria differentiation prerenal from renal ARF in PAN. Method: ARF was defined as serum creatinine >132 ìM/L in presence of normal maternal Atypical/recurrent HUS is a heterogeneous group of disorders. The pathogenesis of a/rec creatinine. Oliguric ARF is urine outpute 1 ml/kg/h. We analyzed Apgar score (< 7), stage HUS is not fully understood. The patients have a bad outcome with a high risk of end stage of HIE and parameters of renal functions: blood Urea, blood Creatinine, urinary Na in renal failure. Disorders with activation of the alternative complement pathway play an mM/L, Creatinine clearance (CrCl) in ml/min/1,73m2, Excreted fraction of filtered sodium, important role regarding outcome and survival. In a small group we found defects in FHR1, (FENa %), Renal failure index (RFI). which is loced at the Chromosom I. FHR1 shoes a high similarety to factor H. Results: During the four year period we admitted 46 term newborns with PAN and different Since the year 2001 we have been evaluated 45 patients with atypical/ recurrent HUS in a stages of HIE. In 16 (35%) we found ARF (5 newborns had renal and 11 had prerenal). multicentre study including Austria, Czechia, Germany, Hungary and Switzerland. Out o f Average recovery time was 4,3±1,5 days in prerenal ARF group and 7,6 days in renal ARF 45 patients 7 (15,5%) children had no FHR1. Age at onset of these 7 children was in median group. One newborn died, with heavy PAN and ARF. There is statistically significant 6.8 years compared to all with the median age of 4.9 years. All patients were demonstraed difference in renal function tests between prerenal and renal ARF (p<0,05). clinical symptoms one month before diagnosis. From these 7 patients 5 had no diarrhoea. Conclusion: Renal indices are good predictors of severity and outcome and differentiating 50% patients developed respiratory infection. During the first episode in 85,7 % dialysis prerenal from renal ARF in asphyxiated newborns. was necessary. In 71,4 % patients were treated with plasmapheresis and 50% reseved furosemid. In 85,7% packed RBC were necessary. Five patients had a recurrent form of HUS. One patient was four times transplanted, only the last transplantation was fortunately successful. The therapy of patients with D--HUS is empiric with plasma substitution during active disease and for prophylaxis. However, many patients progress to ESRD despite continuous plasma therapy. If patients with FHR1 disorder differ from other anderlying deseases can not be presently. To improve outcome and survival of these patients it is necessary to encourage new therapeutic studies based on the ESPN HUS registry (http://espn.uwcm.ac.uk).

Supported by ESPN, APN and Medical University Innsbruck

COD. PP 123 COD. PP 124 Impact of Oxidative Stress on Renal Tubular Abnormalities In FANCONI SYNDROME IN AN EPILEPTIC CHILD ON VALPROIC Egyptian Thalassemic Patients ACID TREATMENT M Zahrane*, N O. Moustafa*, G A. Refaat**, F S El-Din** * Pediatrics Department, Cairo A Bettinelli°, C Zucca*, L Radice*, S Stucchi° °Department of Pediatrics, Mandic Hospital, University. ** Clinical and Chemical Pathology Department, Research Institute of Merate and *Scientific Institute E.Medea, Bosisio Parini (Lecco), Italy Ophthalmology. presenting author: M0na zahrane Department of Pediatrics, Mandic Hospital , Mandic Hospital , 23807 Merate , Lecco Italy , 8 tolombat street, Garden- City, Cairo- Egypt , 564 Cairo- Egypt , Egypt Fanconi syndrome represents a rare side effect of valproic acid treatment (VPA). Usually . Thalassemia major is the commonest form of haemoglobinopathies in Egypt. tissue urinalysis and proteinuria are not requested examinations in the follow-up of children deposition of excess iron are major factors responsible abnormalities found in various renal treated with VPA. tissues. This study is designed to define renal functional abnormalities and provide evidence Case report. The boy had been affected by epilepsy and tetraparesis since 5 months of age that increased oxidative stress is one of the main factors responsible for this damage. Sixty and West syndrome was diagnosed. He had started treatment with VPA since the time o f . Thalassemic children with mean age 9.6 5.1 years, are studied. Patients were divide d diagnosis (median dose, 45 mg/kg/day) always maintaining the serum levels in the into three groups: Group A: including 26 patients with severe disease where Hct < 25% on therapeutic range (40-100 mcg/ml). Clobazam (15 mg/day) had been contemporary regular transfusion, without desferrioxamine therapy. Group B: including 19 patients with administered. After 9 years of continous VPA treatment, urinalysis was performed for feve r severe disease under desferrioxamine therapy: Group C: including 15 patients with and proteinuria (2.09 g/day) and glucosuria (7.1 g/day) were detected. Thereafter moderate disease severity where Hct > 25% ,The result was compared to 22 children served generalized hyperaminoaciduria, increased urinary alpha-1-microglobulin (132 mg/l), as controls. Thalassemic patients showed significantly higher urinary malondialdehyde (p < hypophosphatemia (0.79 mmol/l) and reduced renal tubular re-absorption of phosphates 0.001), and significantly lower urine osmolarity (p < 0.001) as compared to controls. The (24%) were also demonstrated. Glucose tolerance test was normal and Fanconi syndrome three studied groups showed significantly higher levels of urinary proteinuria (p < 0.001), was diagnosed. Among other biochemical results there was an increased alkaline especially LMW fraction: Alpha 1 microglobulin (p < 0.001) compared to controls but only phosphatase (368 U.I/l) with normal serum total calcium (2.32 mmol/l), parathyroid patients with severe disease had significantly higher Beta 2 microglobulin (p < 0.001) hormone (20 pg/ml) and 25 hydroxy vitamin D (30 pg/ml) levels. Liver function was compared to controls. Severity of the disease correlates positively with both levels of normal such as glomerular filtration rate. X-ray examinations revealed osteoporosis and urinary malondialdehyde and urinary LMW proteins, correlate negatively with urine numerous bone fractures with multiple localizations. VPA was discontinued and substitute d osmolarity. Our data confirmed the high frequency of renal tubular dysfunction in . by vigabatrin (50 mg/kg/day), while clobazam was continued. Thalassemia major. Increased oxidative lipid peroxidation mediated by iron overload, We observed a complete remission of Fanconi syndrome, including hypophosphatemia, malondialdehyde which plays a major role necessitating proper follow up of the chelation within 5 months of VPA withdrawal. No further bone fractures were also detected. therapy in thalassemic patients. In conclusion, urinalysis and proteinuria need to be assessed in the follow-up of severely disabled children with epilepsy, receiving a long-term VPA treatment. Pediatr Nephrol (2006) 21:1493–1635 1553

COD. PP 125 COD. PP 126 MANIFESTATION OF ANTENATAL BARTTER SYNDROME TYPE SERUM CONCENTRATION OF CYSTATIN C IN CHILDREN IV WITHOUT SIGNIFICANT POLYURIA WITH URINARY STONES J Höfele* S Hiedl N Jeck M R Benz J Glöckner O Genzel-Boroviczeny L T Weber W M Zoch-Zwierz, L Hackiewicz, T Porowski, A Wasilewska, K Zwierz Dr. von Haunersches Kinderspital , Lindwurmstrasse 4 , 80337 Munich , Germany I Department of Pediatrics, Medical University in Biaùystok, Poland , Waszyngtona 17 , 15- 274 Biaùystok , Poland Bartter syndrome is a group of autosomal recessive salt-losing nephropathies characterized by polyuria with renal salt-losing, hyponatremia, hypokalemia, hypochloremic metabolic Stone formation precedes long period, when the crystals are accumulated in basement alkalosis combined with increased urinary prostaglandins, elevated plasma renin activity, membranes of renal tubules and intestinal tissue. Accumulated, inside of renal tubules and hyperaldosteronism. crystals and stones in urinary tract cause urinary tract obstruction, what may lead to impairment of renal function. Cystatin C level has been used to detect subtle and subclinical We report on a female patient of consanguineous parents: Uterine contractions because of glomerular filtration impairment. Its serum concentration increases earlier than serum polyhydramnios at 25 weeks of gestation. Cesarean section at 31+5 weeks of gestation creatinine concentration. despite of tocolysis and withdrawal of amniotic fluid. 20% weight loss during the first hours The aim of work was the assessment of serum cystatin C concentration in children with of life. Laboratory examination revealed hyponatremia, hypokalemia, and hypochloremic renal stones in comparison to serum creatinine concentration and GFR according to metabolic alkalosis. Diuresis was 4-6ml/kgBWxh and the serum creatinine increased. Schwartz and urinary calcium and oxalate excretion. Assuming an antenatal Bartter syndrome the absence of polyuria was possible due to Material: Examined group (B) consisted of 30 children aged 13.08+4.14 years with urinary dehydration. Indeed, after high fluid intake the patient developed polyuria. Evidence of stones. Control group (C) consisted of 26 healthy children at the same age. increased plasma renin activity, hyperaldosteronism, and increased urinary prostaglandin E2 Methods: Nephelometric method was used to determine serum cystatin C level. and M secretion. With evidence of a homozygous nuc1A1T mutation with loss of the start Results: Serum cystatin C in children from group B was higher than in control group codon in the BSND gene treatment with indomethacin was started after initial symptomatic (p<0.05), with no statistical differences in serum creatinine concentration and GFR therapy. (p>0.05). Particular analysis of the results showed that renal stones of 1 – 1.6 cm diamete r endanger with renal insufficiency, because in 16% of children serum cystatin C exceeded Polyuria can be absent in neonatal Bartter syndrome because of massive dehydration in the 95c values of healthy children. In this group of children GFR was decreased in 13% and first hours of life. increased serum concentration was found only in 3% of children. Values of examine d parameters were normal in children with small renal stones in kidney of diameter 0.35-0.8 cm. Conclusion: Serum cystatin C increases with increased degrees of urolithiasis assessed by stone size and their number in kidney.

COD. PP 127 COD. PP 128 Acute rhabdomyolysis in patients with hypokalemic salt-losing CYSTATIN C: AN EARLIER MARKER OF RENAL FUNCTION tubulopathies LOSS IN CHILDREN R O von Vigier 1, G P Ramelli 2, G D Simonetti 1, M Konrad 1, M G Bianchetti 2 1 A Pota, ML Sirico, A Pota, A Fella, C Pecoraro University Children’s Hospital, Pediatric Nephrology, Inselspital, Berne, Switzerland 2 Santobono Children`s Hospital , Department of NephroUrology, via M. Fiore n° 6 , 80129 Department of Pediatrics, Ospedale San Giovanni, Bellinzona, Switzerland Naples , Italy University Children`s Hospital; Pediatric Nephrology , Inselspital, Freiburgstrasse 10 , 3010 Berne , Switzerland Serum level of Cystatin C (Cys-C), a 13359 Da polypeptide, has been proposed as a marker of glomerular filtration rate (GFR). The aim of this study is to verify the utility of Cys-C Background: measurements to estimate GFR in a paediatric population. In 483 children (M/F 274/209; Rhabdomyolysis is rare in children and mostly results from traumatic, infectious, metabolic, age 8.67±4.86 years) we have measured serum levels of Cys-C (mg/l with nephelometry- ischemic, inflammatory or toxic causes. Hypokalemia represents an infrequent cause of BNIIN-DadeBerihng) and Creatinine, Body weight and height. We have made 1441 rhabdomyolysis, and until recently, only few reports document the association with renal determinations: from 1 to 18 per patient. We included subjects with different values of GF R hypokalemia. Two cases of rhabdomyolysis complicating hypokalemic salt-losing (CrC, Schwartz Formula) divided in five different groups, according to primary tubulopathies are reported. nephropathy (1-Hypo-dysplastic, 2-hereditary-familial, 3-Tubulointerstitial, 4-Vascular, 5- Reports: Glomerular) and compared with healthy subjects (group 0). We excluded patients in renal I. A 4-year old girl, known for antenatal Bartter’s syndrome, presented with severe replacement therapy. Statistical analysis was performed with linear regression; we dehydration and muscle weakness after acute gastroenteritis with repetitive vomiting. Very covariated for age , gender and Body Surface Area. GLM for repeated measures was severe hypokalemia (potassium < 1.5 mmol/l) and increased creatine kinase (2,757 IU/l; performed to evaluate the follow-up. We found that there was a significantly correlation normal: < 154) were noted. The diagnosis of hypokalemic rhabdomyolysis was made and between CrC and serum levels of Cys-C for each group. intravenous fluid and potassium substitution initiated. Very large amounts of potassium We compared the two estimation of renal function methods with multiple determinations chloride (18 mmol/kg daily) were used to rise plasma potassium above the limit of detection during the follow-up (up to 7 in 36 months). 51 subjects of the group-1 with normal renal (1.5 mmol/l). Symptoms resolved within days; no signs of acute renal failure occurred. function at the first observation (T0) were divided in two subgroups: GROUP A: 23pts, II. An 18-year-old boy with a two-day history of diarrhea presented with mild dehydration 18M, with normal CrC and normal levels of Cys-C at T0 (113±15 and 0.8±0.06, and generalized muscle tenderness. Creatine kinase was increased (20,850 IU/l), creatinine respectively), kept normal values of CrC (106±7) and increased values of Cys-C (0.98, and potassium normal. One week later he felt well. Creatine kinase was normal but p<0.05) at the end of the follow up; GROUP B: 28 pts, 18M, with normal values of CrC potassium reduced (3.1 mmol/l). A detailed history revealed frequent musculoskeletal (108±7) and high levels of Cys-C (1.08±0.17) at T0, had a decrease of CrC (69±15, p<0.05) symptoms. The provisional diagnosis of Gitelman’s syndrome was corroborated by at the end of 36 months follow up and a greater increase of serum levels of Cys-C demonstrating normal blood pressure (105/65 mm Hg), alkalosis (bicarbonate 35 mmol/l), (1.61±0.51, p<0.005)). hypomagnesemia (0.54 mmol/l), inappropriate chloriduria, and hypocalciuria. Conclusions: 1. Physicians should be aware of the possibility of rhabdomyolysis in hypokalemic salt- losing tubulopathies. 2. In hypokalemic tubulopathies, rhabdomyolysis can complicate acute intestinal diseases. 3. Rhabdomyolysis may occur before diagnosis of the tubulopathy. 1554 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 129 COD. PP 130 TUBULAR AND GLOMERULAR FUNCTION IN MAJOR EPIDEMIOLOGICAL CHARACTERISTICS AND CLINICAL THALASSEMIA PRESENTATION OF GITELMAN SYNDROME IN SPANISH SIMIN SADEGHI BOJD CHILDREN ZAHEDAN MEDICAL SCIENCES , PEDIATRIC /ALI EBNE ABITALEB HOSPITAL , JD Herrero-Morín, J Rodríguez, F Santos, and Collaborative Spanish Study Group on 9816743111 ZAHEDAN , SISTAN&BALOOCHESTAN Iran Gitelman Syndrome in Children. Hospital Universitario Central de Asturias. Universidad de Oviedo , Pediatria. Facultad de Medicina. Julian Claveria 6 , 33429 Oviedo , Asturias Spain Introductin Thalassemia is a heterogenous groups of disease and are the most common genetic disorder BACKGROUND. Gitelman syndrome is a primary tubular disorder caused by inactivating on a worldwide basis.The selective pressure that have the thalassemia so common are not mutations in the SLC12A3 gene that encode the thiazide-sensitive sodium-chloride known but are assumed to relate to the geographic distribution of malaria. Children with cotransporter. It is characterized by hipokalemic metabolic alkalosis, hypomagnesemia, and thalassemia have a shorter red cell life , fetal hemoglobin in their red cell until an older age hypocalciuria associated with renal magnesium and potassium leakage. In this preliminary than normal and red cell that are sensitive to oxidation stress.Shortened red cell life span report we describe the clinical and epidemiological characteristics of Gitelman syndrome in and excess iron cause functional and physiological abnormalities in various organ systems Spanish pediatric population. in thalassemic patients. The severity correlated with the degree of anemia , hyper PATIENTS AND METHODS. A questionnaire requesting information on children transfusion and iron chelating therapy diagnosed as Gitelman’s syndrome was sent to all Pediatric Nephrology units of Spain. Based on the responses, 45 Spanish children (25 females) from 15 of those units were This study is designed to define renal tubular and glumerolar abnormalities with beta included in the study. Quantitative data are expressed as mean (SD). thalassemia and to correlate the renal finding with clinical parameters. RESULTS. Age at diagnosis was 8.5 (3.9) years (range 0.6-18.8). Muscular cramps were Methods: the presenting manifestation most often found (18 cases). Eleven patients (24%) were diagnosed by familiar study of the syndrome and in 9 cases (20%) the diagnosis resulted One hundred sixty six patients (mean age 13.34) , mean weight (31.78) were studied .The from a casual finding. Weight (n=43) and height (n=42) Z-scores at diagnosis were -0.6 patients were 96 male (57.8%) and 70 female (42.8%) .24 hours urine secretion was (1.2) and 0.6 (1.3), respectively. Plasma potassium and magnesium concentrations were 2.8 collected and was examed for level of Na , K , Creatinin , Mg , Uric acid , Beta 2 (0.6) mEq/l and 1.4 (0.3) mg/dl. Fractional excretions (%) of potassium (n=36) and Microglobulin , Protein , Ca and Phospharose. magnesium (n=31) were 23.6 (17.4) and 7.8 (11.2), respectively. Urine calcium/creatinine Result: ratio was 0.04 (0.05) mg/mg (n=37). 78.3% of patients had normal GFR and 21.7% had abnormal GFR. The mean of tubular CONCLUSIONS. This series contains the greatest number of pediatric cases of Gitelman´s parameters such as protein , phospharose , Uric acid , Na , Beta 2 Microglobulin , were syndrome ever reported and provides useful information on clinical and biochemical higher than normal level .Significantly higher levels of Uric acid , P , Na , Beta 2 MG , presenting manifestations of the disease in children. Studies to further characterize the were found compared with normal level. phenotype and genotype of Gitelman syndrome in this population are ongoing. Discusson:

Correlation was not found between serum ferritin and urine parameters.(p<0.01). We do not know that the degree of renal dysfunction correlated to response to therapy (Iron chelation) , frequent transfusion and/or splenectomy , or not? Further study in particular long term follow up in thalassemic patients after efficient iron chelation and hypertransfusion is needed to clarify our observation.

COD. PP 131 COD. PP 132 Nephrogenic syndrome of inappropriate antidiuresis (NSIA) Isolated massive proteinuria following Acid Valproic therapy G Blanchard1, D Morin2, J F Delobbe1, G Geelen3, A Charrie4, E Javouhey5, J M André1, C Pietrement J Motte B Roussel Hôpital Américain-CHU de Reims-France P Cochat1, B Ranchin1 1. Département de Pédiatrie, 3. Laboratoire d`Exploration Hôpital Américain-CHU de Reims , Pediatrie A 47 rue Co gnacq-Jay , 51092 Reims , France Fonctionnelle Endocrinienne et Métabolique, 5. Service de Réanimation Pédiatrique, Hôpital Edouard-Herriot - Lyon, 4. Service de Radioanalyse, Centre Hospitalier Lyon-Sud, A 6-year-old girl presented with a massive proteinuria (6g/l) discovered on routine 2. Département de Pédiatrie, Hôpital Arnaud de Villeneuve, Montpellier - France urinalysis. Since four years old, she had been treated for partial frontal epilepsy. Her Département de Pédiatrie, Pavillon S , Hôpital Edouard Herriot , 69437 Lyon , France medications included Valproic Acid and gabapentin begun two years earlier with good control on epilepsy. Examination revealed a child in good condition, with no development Mutations of the arginine vasopressin (AVP) V2 receptor (V2R) gene responsible fo r delay. The laboratory results showed an isolated tubular proteinuria. The serum constitutive activation of V2R and NSIA has been recently reported in two patients. We concentration of proteine was 70g/l, albumine 40g/l, creatinine 35 mmol/l, urea 5,4 mmol/l, report on a boy who presented with two severe episodes of hyponatremia at 10 and 34 sodium 136 mmol/l, potassium 4.5 mmol/l, chloride 104 mmol/l, bicarbonate 27 mmol/l, months of age, which both occurred during seasonal heat wave. The first attack consisted of phosphore 1,36 mmol/l. In urine reabsorption of phosphate was 89%, b2 microglobuline status epilepticus and the second of atypical absence. Laboratory investigations revealed 0.13mg/l, calcium/creatinine 0.1 mmol/mmol. There were no hematuria, no severe hyponatremia (nadir 123 mmol/L), low plasma osmolality (nadir 253 mosmol/kg), hyperaminoaciduria, no glycosuria. The urinary protein electrophoresis confirmed the normal urine sodium fractional excretion and inappropriately elevated urine osmolality tubular aspect of the proteinuria (6g/l). Valproic Acid adverse effect was suspected, it was (nadir 420 mosmol/kg), consistent with a syndrome of inappropriate antidiuretic hormone discontinuated and replaced by oxcarbazepine and topiramate because of gabapentin secretion (SIADH). However plasma AVP was undetectable at the time of the secon d inefficiency. Six months after Acid Valproic discontinuation, the proteinuria had episode, therefore suggesting a constitutive V2R activation. A missense R137C mutation o f disappeared. After 3 years follow up, the tubular function is normal. Acid Valproic is V2R gene (already published) was identified both in the patient, his asymptomatic 9 year- known to give reversible Fanconi syndrome, some minor tubular dysfunction have been old brother (hemizygous), and their mother (heterozygous). Neurological acute symptoms also described. When done, biopsy reveals giant mitochondria in proximal tubular cells, or and hyponatremia recovered without sequelae in our patient after fluid restriction. A cousin tubulointerstitial nephritis. Incidence, delay of apparition, individual susceptibility, of the mother was known to suffer from chronic encephalopathy with repeated seizures due physiopathology of this Acid Valproic adverse effect, unique to children have not been to hyponatremia; sequencing of the V2R gene showed the same R137C mutation both in elucidated yet. Our observation is remarkable by the intensity of the isolated tubular this child and his mother. Such a pedigree focuses on a new cause of severe hyponatremia proteinuria in a not disabled child. to be investigated in the presence of a condition consistent with SIADH but with low plasma AVP concentration. Further studies are mandatory in order to set up the effects o f such a gain in V2R function and to explain the different phenotypes. Pediatr Nephrol (2006) 21:1493–1635 1555

COD. PP 133 COD. PP 134 Acute renal tubular necrosis in hepatitis A Mitochondrial DNA duplication / deletion presenting as a Fanconi MK Lee (presenting author)1, JH Lee1, YM Cho2, YS Park1 (1)Department of Pediatrics, syndrome with myopathy and pigmentary retinitis Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Korea (2) 1 F Cachat, 2 F Farron, 3 F Munier, 4 C Hinard, 4 MA Morris, 5 S Jacquemont Department of Pathology, Asan Medical Center, University of Ulsan, College of Medicine, 1Department of Pediatrics, Division of Pediatric Nephrology, University Hospital, Seoul, Korea Lausanne, Department of Pediatrics, 2Regional Hospital, Delemont, 3Hôpital Jules Gonin, Asan Medical Center , Department of Pediatrics, Asan Medical Center Pungnap 2(i)-dong University Eye Hospital, Lausanne, 4Service of Medical Genetics, University Hospital, Songpa-gu , 138-736 Seoul , South Korea Geneva, 5Department of Medical Genetics, University Hospital, Lausanne, all in Switzerland Introduction: Clinical courses of hepatitis A infection is usually mild and improves without Department of Pediatrics, University Hospital , Rue du Bugnon , 1011 Lausanne , Vaud complication. Acute renal failure after hepatitis A infection is very rare. We report a patient Switzerland with acute renal tubular necrosis after hepatitis A infection. Case: A previously healthy thirteen-year old girl was admitted due to anorexia and vomiting Background / aim of the study after school camp. She had not experienced oliguria nor weight gain. Blood pressure was Mitochondrial DNA (mtDNA) deletions have been described in patients with Fanconi 149/80 mmHg. She was not icteric. Neither liver nor was spleen palpable. No edema was syndrome and respiratory chain disorders (complexes I, III, IV and V), but the role of noticed. On laboratory examination BUN/Cr was 78/6.5 mg/dL, AST/ALT 1104/ >1375 mitochondrial duplication is less understood. No concomitant duplication/deletion of IU/L, total and direct bilirubin 2.9/1.4 mg/dL. On urinalysis albumin was negative, RBC mitochondrial DNA has been described in patients with Fanconi syndrome, except in cases 3~5/HPF, WBC 0~2/HPF and amorphous urate positive. HAV IgG/IgM was of Kearns-Sayre syndrome. negative/positive, HBs Ag negative, HCV Ab negative. Both renal cortical echogenecity was increased on renal ultrasound. Renal biopsy revealed focal tubular epithelial Case presentation degeneration and trivial interstitial mononuclear cell infiltration which was compatible with The patient presented at seven years of age with acute severe muscle cramps. Laboratory acute tubular necrosis. Blood pressure was controlled after administration of amlodipine. and biochemical analysis are : Nine days after admission, BUN/Cr decreased to 12/1.1 mg/dL, and AST/AlT 36/78 IU/L. Conclusion: We report a case of acute renal tubular necrosis accompanied with hepatitis A Plasma (in mmol/l): Na 139, K 2.8, Ca 2.17, PO4 0.85, Mg 0.3, CK 496, lactate 3.1, infection which subsided spontaneously without complication. creatinine (micromol/l)61.

Urine (mmol/l): Na 127, K 42, Ca 3.1, PO4 4.4, Mg 5.3

Full blood count with differentiation was normal. Glycosuria and generalized aminoaciduria were present on urinalysis. Pyruvate dehydrogenase and citrate synthase activities were normal. Ophthalmic examination revealed retinitis pigmentosa. Liver biopsy was normal; muscle biopsy showed rare ragged red fibers.

Genetic analysis of mtDNA of the patient revealed heteroplasmic deletion and deletion/duplication mutations, in increasing proportions in fibroblasts, muscle and liver. Genetic analysis of the mother is underway. More than a year later, the patient’s glomerula r and tubular functions are stable, but her vision and muscle strength are slowly deteriorating.

Discussion To our knowledge, this is the first case of a Fanconi syndrome with mtDNA duplication and deletion. As it has been hypothesized (Poulton J et al. Hum Mol Genet 1993;2:23-30), we suggest that the large-scale mtDNA duplication that the patient has might have predisposed her to mtDNA deletions and the appearance of Fanconi syndrome.

COD. PP 135 COD. PP 136 Amiloride reduces Kaliuria in Nephropathic Cystinosis (NC) Renal tubular acidosis (RTA), nephro calcinosis, and diabetes insipidus M D Sinha (Presenting author), G B Haycock, S P A Rigden Affiliation: Evelina Children`s (DI) in asymptomatic teenage girl with primary Sjogren syndrome Hospital, Guy`s & St Thomas`s NHS Foundation Trust (pSS) Evelina Children`s Hospital, Guy`s & St Thomas`s NHS Foundation Trust , Department of R Bogdanovic, J Putnik, N Stajic, B Nikolic-Bonaci, J Markovic-Lipkovski, G Basta- Paediatric Nephrology, Room 64, Sky Level, ECH, St Thomas`s Hospital, Lambeth Palace Jovanovic, A Af gan Road , SE1 7EH London , UK Institute of Mother and Child Health Care of Serbia , 8 R. Dakica St , 11070 Belgrade , Serbia Serbia & Montenegro Kaliuria as part of Fanconi syndrome in NC is universal but varies in severity. Renal losses of potassium are often severe and clinicians struggle to achieve sustained normal plasma Renal involvement is common in adults with SS, but in children has been described only potassium levels despite active replacement. Administration of potassium salts is rarely. complicated by the large volumes required, poor palatability of compounds and risks of Among 135 pediatric SS cases reported to date, RTA has been recognized in only 12; DI gastrointestinal complications. Objectives: The use of amiloride as a therapeutic was the most frequent renal comorbidity whilst interstitial nephritis was the predominant intervention to reduce kaliuresis. Methods: Prospective analysis of two patients with long histopathological finding. We present the teenage asymptomatic girl with pSS in whom standing NC started on amiloride. Results: Potassium supplementation before amiloride diffuse “tubulopathy” from interstitial nephritis was found. treatment was 4mmol/kg/day in Patient 1 and 12.9mmol/kg/day in Patient 2; pre-treatment In 13-yr old asymptomatic girl bilateral nephrocalcinosis was incidentally found. History kaliuria was 3.3mmol/kg/day in Patient 1 and 9.5mmol/kg/day in Patient 2. Treatment with revealed polyuria and polydipsia of uncertain duration. Clinical and laboratory examination 0.23 mg/kg/day of amiloride in Patient 1 resulted in an increase in plasma potassium of 0.6 disclosed: DI, distal RTA (NH4Cl loading: UpH 6.84, TA and NH4+, 19 and 15.4 mmol/l by day 7 despite reducing potassium supplements by 1.0 mmol/kg/day, equivalent µmol /min/1.73m2, respectively; NaHCO3 loading: FEHCO3- 1.8%; U-B pCO2 after oral to 40ml per day. After 1.4 years therapy, when taking 0.33 mg/kg/day of amiloride, plasma NaHCO3 load: 3.5 mmHg), hypercalciuria (8.8 mg/kg), tubular proteinuria 540 mg/24hr, potassium was 0.5 mmol/l higher than pre-treatment values with a reduction of 1.6 increased B2-microglobulin), and mild hyperaminoaciduria; ESR was 35 mm, RF>200 mmol/kg/day, or 60ml per day in potassium supplements. Patient 2 received 0.40 mg/kg/day IU/mL, IgG >30 g/L; ANA, anti-SS-A (203.4 IU/mL), and anti-SS-B were positive; of amiloride and by day 7 of treatment had an increase of 0.2 mmol/l in plasma potassium negative were: anti-dsDNA, anti-Sm, anti-RNP, ANCA, HBsAg, anti-HCV, and HIV. on a reduced dose of potassium supplements (64 ml/day less, equivalent to 2.6 Diagnosis of pSS was substantiated by positive parotid glands scintiscan, by elevation of mmol/kg/day). Potassium supplementation was reduced in Patient 1 by 40% after 1.4 years serum amylases and by interstitial nephritis with lymphocytic infiltrates found on biopsy. therapy and by 20% in Patient 2 by 7 days. No adverse effects were observed. Conclusion: Bicytra treatment led to correction of acidosis, hypercalciuria, and hypokalemia. Prednison Amiloride may have a therapeutic role in patients with NC with severe kaliuria. was introduced for interstitial nephritis. SS should be considered in the older child, particularly female, with otherwise unexplained RTA. Careful search for other tubular dysfunctions is necessary whilst renal biopsy may help to assess the extent of renal damage and the need for immunomodulatory therapy. In our pt, impaired tubular H+ handling seems to point out to a secretory defect. 1556 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 137 COD. PP 138 RENAL FUNCTION IN PEDIATRIC PATIENTS WITH BETA Tenofovir-related nephrotoxicity : re port of two cases and urine Beta2- THALASSEMIA MAJOR microglobuline analysis in a series of 34 HIV infected children receiving M Mazaheri, pediatric nephrologist, Ass.professor of semnan medical university(main this treatment. author) MR Rezvani,hematologist,Ass professor of semnan medical university SH Musavi , R Salomon, M Dechaux, A Papaleo, S Blanche Pediatric Department Hôpital Necker pediatrician Enfants Malades, Paris, France Presenting author: R Salomon amir hospital , imam hosein sq.amir hospital pediatric ward , 1453773141 semnan , semnan Université René Descartes , Hôpital Necker 149, rue de Sèvres , 75015 Paris , France Iran Tenofovir, a nucleotide analog , has recently be introduced as a component of active Introduction antiretroviral therapy (ART). This study reports on 2 cases of tubulopathy revealed by In patients with thalassemia major. the most important cause of morbidity & mortality is polyuro-polydipsia and hypophosphatemia in 2 HIV infected children receiving tenofovir. organ failure due to iron deposits, desferioxamine toxicity & anemia. This study was Serum concentrations of tenofovir were in the normal range. Data obtained before (M0) and designed to define renal abnormalities associated with thalassemia & to find early marker 3 and 7 months after tenofovir had been interrupted are indicated below. (markers) of renal dysfunction. In both cases GFR was normal; signs of proximal tubulopathy were present in patient A but Patients & Method not in patient B. Hypophosphatemia regressed after discontinuation of tenofovir in both 39 thlassemic children (18 female & 21 male) with mean age of 11.8 yr. 2.3 yr. were patients, as well as polyuria. Urine beta2-microglobuline remained elevated. Moreover, we studied. All of them were received desforioxamine. 22 age & sex matched healthy children found on a series of 34 HIV infected children who received tenofovir, an elevation of urine were involved in the study. Blood & timed urine sample were obtained for hematologic & beta2-microglobuline in 9, while it was elevated in only one among 42 HIV infected biochemical tests. The results were compared between case & control group. children who received other antiretroviral medications. These data call for a careful supervision of clinical symptoms of tubulopathy in patients receiving ART with tenofovir. Results Mean value of BUN, Serum Creatinine, Creatinine Clearance, Serum electrolytes, Urine osmolality, fractional excretion of sodium & potassium were not statistically different between two groups. Level of urinary NAG (N - acetyle - beta - d - glycosaminidase) was significantly higher in patients than in controls. (P : 0.000) There was a positive relation between urinary NAG & duration of disease. (P: 0.04). The was no statistically significant relation between urinary NAG & Serum ferritin. Tubular function was not altered by hypertransfusion.

Conclusion Proximal tubular dysfunction is found in thalassemic patients. Measuring urinary NAG Can guide the physician to find the early tubular abnormality in patients without frank renal dysfunction. Severity of the abnormalities is correlated with the duration of disease.

COD. PP 139 COD. PP 140 Complete Deletion of CLCNKB Gene Asociated with Bilateral Renal NEONATAL BARTTER SYNDROME WITH Cysts Lesion in Bartter Syndrome NEPHROCALCINOSIS; New Mutation on SLC12A1 Gene E Demirkaya1 (Presenting Author) N Jeck2 F Gok3 1Hacettepe University Faculty of 1F Gok (Presenting Author) 2N Jeck 3E Demirkaya 1Gülhane Military Medical Academy, Medicine, Department of Pediatrics, Pediatric Nephrology and Rheumatology Unit, Ankara, Department of Pediatric Nephrology, Ankara, Turkey 2University Children Hospital, Turkey 2University Children Hospital, Department of Pediatrics, Philipps University of Department of Pediatrics, Philipps University of Marburg, Marburg, Germany 3Hacettepe Marburg, Marburg, Germany 3Gülhane Military Medical Academy, Department of University Faculty of Medicine, Department of Pediatrics, Pediatric Nephrology and Pediatric Nephrology, Ankara, Turkey Rheumatology Unit, Ankara, Turkey Hacettepe University Faculty of Medicine, Department of Pediatrics, Pediatric Nephrology Hacettepe University Faculty of Medicine, Department of Pediatrics, Pediatric Nephrology and Rheumatology Unit, Ankara, Turkey , Hacettepe University Faculty of Medicine, and Rheumatology Unit, Ankara, Turkey , Hacettepe University Faculty of Medicine, Department of Pediatrics, Pediatric Nephrology and Rheumatology Unit, 06100-S›hiye Department of Pediatrics, Pediatric Nephrology and Rheumatology Unit, 06100- Ankara, Turkey , 06100 Ankara , Turkey S›hiyeAnkara, Turkey , 06100 Ankara , Turkey

Bartter syndrome is characterized clinically by normotensive hyperreninism, Neonatal Bartter syndrome is observed in newborn infants and characterized by hyperaldosteronism, and hypokalemic, hypochloremic, metabolic alkalosis. Chronic polyhydroamniosis, premature delivery, life-threatening episodes of fever and dehydration hypokalemia can induce renal structural and functional abnormalities including a during the early weeks of life, growth retardation, hypercalciuria, and early-onset of concentrating defect, interstitial fibrosis and/or chronic inflammation, and renal cyst nephrocalcinosis. formation. Herein we describe a patient with Bartter syndrome who exhibited renal cysts A 3-year-old girl was born preterm (in 32 weeks of gestation) from unconcogious parents. along with complete deletion of the CLCNKB gene. During prenatal period, the presence of polyhydroamniosis was noticed. She presented the A 16-year-old girl was referred to our hospital because of growth failure, vomiting, symptoms of vomiting, polyuria, failure to thrive, and fever when she was 2 months old. On constipation and polyuria when she was six month old . The patient was born at 38 weeks of physical examination she had cousmaul respiration with no signs of cyanosis. She also has gestation, and her birth weight was 3.1 kg. The prenatal course was unremarkable with growth retardation (height and weight < 3%). Laboratory studies revealed metabolic polyhydramnios. Physical examination revealed a height of 150 cm (3-10 %) and weight of alkalosis, hypokalemia, hypochloremia, an elevated plasma renin activity, and 37 kg (< 3 %). Her blood pressure was 100/60 mmHg. Laboratory studies revealed hypercalciuria. On USG it is noticed that she had nephrocalcinosis. Molecular analysis of metabolic alkalosis, hypokalemia, hypochloremia. She was diagnosed with Bartter the SLC12A1 gene (encoding the Furosemide-sensitive Na-K-2Cl co-transporter of the loop syndrome. At regular follow-up she developed bilateral renal multiple cystic lesions of Henle) identified a homozygous H676Y (tyrosine for histidine) exchange. Treating the detected by renal computed tomography (CT) and renal ultrasound when she was 14 years patient with indomethacin and potassium supplementation resulted in the normalization of old. The moleculer analysis of the patient has indicated a complete deletion of the plasma ion abnormalities and polyuria. Her hypercalciura has not been resolved but CLCNKB gene. nephrocalcinosis has not progressed and renal stones have not form during 3 years of There has been only one case in literature that indicates mutation analysis in renal cyst follow-up. formation with type III bartter syndrome. There are also only two cases that have been Neonatal Bartter syndrome is an autosomal recessive disorder, and recent molecular biology reported about Bartter syndrome with complete deletion so far. But a case of complete findings have demonstrated that most of these patients have an inherited defect in NaCl deletion together with renal cyst formation has not been not shown. transport in the distal nephron. There has been only one case that indicates mutation analysis in nephrocalcinosis patients with bartter syndrome so far. Our case is the second one in this group and we have identified a new type of mutation. Pediatr Nephrol (2006) 21:1493–1635 1557

COD. PP 141 COD. PP 142 A DIFFICULT CASE OF NEONATAL BAR TTER SYNDROME The incidence of urolithiasis in childhood renal tubular disorders and Z Bircan, N jeck, S Tugay, F Harputluoglu hyperoaluria Kocaeli University , Kocaeli University Faculty of Medicine Pediatric Nephrology AJ Al Mosawi Department Umuttepe , 41380 Kocaeli , Turkey University hospital in Al Kadhimiyia , Al Kadhimia , 70025 Baghdad , Iraq

Two month-old boy born 33 week gestation was sent to our hospital with the diagnosis of Renal tubular disorders (RTDs) include: global proximal tubular reabsorption disor-ders Bartter Syndrome. His birth weight was 1920 g. His family history revealed severe (Fanconi syndrome), with cystinosis being the most frequent cause in which lithiasis or polyhydramnios, premature delivery and death of three children. At the age of two months nephrocalcinosis are very uncommon, specific tubular disorders : renal tu-bular acidosis, while his body weight was 1820 g, he required 11.7 mEq/kg/day NaCl, 8.6 mEq/kg/day hypercalciurias including idiopathic hypercalciurias,hypercalciuria due to Bartter syndrome, KCl and 260 cc/kg/day water together with medications of 5mg/kg/day indomethacin and 4 , cystinuria, and X-linked hypophosphatemia.Primary hyperox-aluria is not a tubular mg/kg/day spironolactone. While he was taking this replacement and medications, his disorder, but is a important genetic cause of childhood lithiasis in and was added to this laboratory tests revealed 135 mEq/l Na, 3.3 mEq/l K, 71 mEq/l Cl, 46 mEq/l HCO3, 7.66 series. The aim of the study is study the incidence of urolithi-sis/nephrocalcinosis in PH, 113 mEq/l urine Na, 1.55 mg/mg urine Ca/Cr and 134 mEq/l urine Cl. BERA revealed children with RTDs and hyperoxaluria. sensorineural hearing loss. Patients and Methods: From June 2000 to June 2005, it was possible to evaluate 33 Mutation analysis was performed at the University Children Hospital Marburg, Germany, children; 22 males (67%) and 11 females (33%) with RTD or hyperoxaluria to deter-mine and revealed a large deletion of BSND gene (encoding the beta- subunit of the ClC-K the incidence of urolithisis.Their ages at referral ranged between 4 months and 14 years channels). The deletions which include exon 2-4 of BSND were not described before. (Mean 4.78 years). Although he had fever and vomiting attacks, his sucking and breast feeding were Results: Urolithiasis or nephrocalcinosis (lithiasis group) were found in 20 patients pa exclusively good. He is now 5 months old, 3350 g weight and requires 73 mEq/kg/day (60%) including 9 patients (27%) with idiopathic hypercalciurias (IH),5 patients (15%) with NaCl, 15 mEq/kg/day KCl and 570 cc/kg/day water. Because of very high NaCl and water cystinuria,and 5 patients (15%) with renal tubular acidosis (4 distal, and 1 proximal), and requirements, continuous infusion of NaCl, KCl and water were performed via gastrostomy. one patient with primary isolated hyperoxaluria. This case is presented because of the newly described deletion of the BSND gene which Conclusion: Urolithisis occurred in 60% of children with RTD in this sample with (IH) the includes ¾ of total gene. Although it seems fatal with an extremely large amount of NaCl most commonly RTD associated with urolithisis. and water requirement the baby is resisting surviving. Key words: Urolithisis-Children; renal tubular; disorders.

COD. PP 143 COD. PP 144 Glucocorticoid induced osteoporosis and bone markers in children with TOPIRAMATE INDUCED METABOLIC ACIDOSIS AND steroid sensitive nephrotic syndrome INCREASED RISK OF NEPHROLITHIASIS S A Bakkaloglu A A ytekin S Gonen O Soylemezoglu H Peru E Hasanoglu N Buyan G. Pavone*, F. Leone*, M.M. D’Alessandro*,M.C. Sapia* , C. Corrado*, G. Santangelo°, Gazi University , Department of Pediatric Nephrology Besevler , 06500 Ankara , Turke y F. Vanadia°,S. Maringhini* *Nefrologia Pediatrica,° NeuroPsichiatria Infantile. Ospedale G. Di Cristina. Palermo Idiopathic nephrotic syndrome in childhood well responds to steroid therapy. Due to the OSPEDALE DEI BAMBINI , PIAZZA MONTALTO , 90100 PALERMO , Ital y relapses, steroids are repeatedly used and eventually glucocorticoid induced osteoporosis (GIOP) may develop. Osteoprotegerin and receptor activator of NF kappaB-ligand (RANK- INTRODUCTION: Topiramate (TPM) is a new drug widely used in epilepsy; TPM L) levels are accepted as novel markers of GIOP. produces a weak inhibition of carbonic anhydrase in the proximal tubule. The association between TPM and metabolic acidosis (MA) is well documented; but recently an increased We aimed to evaluate bone metabolism in our steroid responsive nephrotic syndrome risk of urolithiasis has been reported. Only a few cases have been reported in children. (SRNS) patients. 21 patients aged 7.2±3.2 years and 22 age and sex-matched control MATERIALS: In the last 18 months we observed 7 children, in treatment with TPM, subjects were enrolled into the study. Besides serum levels of bone markers including affected by renal tubular abnormalities. vitamin D, parathormone (PTH), alkaline phosphatase (ALP), OPG and RANK-L levels Four children (2 boys and 2 girls, 9-12 years old) were admitted for colicky flank pain. One were also determined and compared to controls. Bone mineral densitometry (BMD) was had documented urolithiasis, 1 had microlithiasis. Two had gross hematuria, hypercalciuria performed in the patient group. Any correlation between cumulative steroid dosage and and MA. bone markers were tested. Other two children had only a MA. One girl, 18 months old, who developed irritability presented: hypercalciuria (Cau/Cru 0,66), mild MA, mild glicosuria, proteinuria and The mean age at diagnosis was 3.6±2.3 years. There were no growth retardation or obesity. elevated urinary alfa-2 microglobulin levels. Glomerular filtration was normal in all All patients were in remission but 8 of whom on steroid. Cumulative steroid dosage was children. 431±302 mg/kg. Vitamin D, ALP and PTH levels were normal. OPG and RANK-L levels MA disappeared when we stopped therapy with TPM. Urinary calcium excretion returned were not different between the patient and control groups (OPG:9.0±4.0 vs 8.0±3.3 u/l, within the normal levels in the patients with hypercalciuria treated for three months with K- p>0.05 and RANK-L: 1337±1480 vs 1433±1376 pg/ml, p>0.05) as well as steroid and citrate. In the girl with urolithiasis the stone disappeared. steroid-free groups. The mean z score was -0.4±0.9. There were no correlation between CONCLUSION: According to our experience, we recommend to evaluate the tubular cumulative steroid dosage and any bone parameters including OPG, RANK-L levels or function in all children in TPM therapy. BMD z score.

Despite repeated course of steroids, we observed highly preserved bone parameters without supplemental vitamin D therapy in our SRNS patients. We emphasize that GIOP may not be a serious problem in this patient group due to the rapid conversion to alternate-day steroid therapy following a short-term daily therapy until remission. 1558 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 145 COD. PP 146 RENAL TUBULAR DYSFUNCTION IN THALASSEMIC Unilateral postnatal renal pelvis dilatation, result of two years follow- CHILDREN up. M. M. D’Alessandro*, F. D’Anna°, C. Corrado*, F. Leone*, G. Pavone*, M.C. Sapia*, Cs Bereczki,H Orvos,E Kukla,J Bakki,V Sumegi, K.Füzesi, S.Túri G.B. Ruffo°, M. Capra°, F. La Rocca*, M. Petrarulo^, M. Marangella^ ,S. Maringhini*. University of Szeged , Department of Paediatrics , H-6720 Szeged , Hungary Nefrologia Pediatrica*, Servizio di Talassemia°. Ospedale G. Di Cristina. Palermo Laboratorio Calcolosi Renale. Ospedale Mauriziano. Torino The upper collecting system dilatation of the urinary tract is the most frequently detected Nefrologia Pediatrica Ospedlae G. Di Cristina , Piazza Montalto , 90100 PAlermo , Italy anomaly by foetal and postnatal ultrasound (US) scanning. The natural history of these abnormalities is not clear. The purpose of this study was to determine the natural course of INTRODUCTION: The association between renal tubular dysfunction and beta-thalassemia mild to moderate unilateral renal pelvis dilatation without any other urinary malformation. minor is well documented; however few data are available on tubular dysfunction in In this prospective single centre study, unselected 9650 newborn babies were screened. The patients with thalassemia major (TM). The aim of the study was to investigate tubular neonates with unilateral pelvic dilatation ee 7 anterior-posterior diameter (APD) 20 mm proximal dysfunction in patients with TM. were (grade 1: 7 mm ee APD 10 mm, grade 2: 11 mm e APDee 15 mm, grade 3: 16 mm MATHERIALS AND METHODS: Twenty-three patients affected by TM and twenty-three sex and age-matched healthy subjects were enrolled in the study. Blood and 24-hour urine APDe 20 mm) without any other renal and urinary tract malformation enrolled and samples were obtained in all children to evaluate renal tubular function. followed up for 24 months with serial US. Complete 24-month follow-up data were RESULTS: In patients with TM urinary alfa1- levels and beta-2 levels were significantly obtained 167 patients, 122 of them observed on the prenatal US. The first postnatal US have higher in comparison to healthy children (51.2±18.2. vs 4.3±1.1 mg/l and 19±3.5 vs discovered dilatation in 45 out of 169 (27.95%) newborn babies with negative foetal 0.15±0.04 mg/l respectively). Hypercalciuria was found in all patients affected by TM, with screening. The renal pelvis dilatation was not detectable (APD 5 mm) in 139 infants mean values of Cau/Cru 0.26 ± 0.01 vs 0.069 ± 0.03 of control group. (83.24%) at the end of study. (24 month of age) There was significant difference in the CONCLUSION: According to our experience tubular dysfunction could be found in all kinetics of spontaneous resolution of pelvis dilatation in Grade 3 comparing to Grade 1 and patients affected by thalassemia (minor and major). 2 groups. At the endpoint 28 out of 167 patients still have significant upper collecting system dilatation including 15 with proved nephro-uropathy (VUR, PUJS). In patients with Grade1 and Grade 2 dilatations we do not recommend to start antibiotic prophylaxis and perform VCUG unselectively, but in Grade 3 group these may be beneficial.

COD. PP 147 COD. PP 148 Fetal Ultrasonography od Urinary Tract Abnormalities Chemokine receptor CCR-1 antagonist prevents epithelial- J Laubova mesenchymal transition after unilateral ureteral obstruction Masaryk`s Hospital Usti nad Labem , Socialni pece 3316/12A , 401 13 Usti nad Labem , B Lange-Sperandio1, A Trautmann1, O Eickelberg2, A Jayachandran2, B Rodenbeck1, M Czech Republic Hömme1, R Horuk3, F Schaefer1 1Department of Pediatrics, Ruprecht-Karls-University, Heidelberg, Germany. 2Department of Medicine II, University of Giessen, Germany, The presence of oligohydramnion, an elevated alpha-fetoprotein concentration in maternal 3Department of Immunology, Berlex Biosciences, Richmond, CA, USA serum, a small for date fetus and a positive family history of renal disease are specific University of Heidelberg , Department of Pediatrics , 69120 Heidelberg , Germany indications to perform prenatal ultrasonographic examination of the urinary tract. In the years 1993-2005 were performed fetal sonographic examinations of urinary tract in Background. Urinary tract obstruction during renal development leads to tubular atrophy 665 fetuses. The majority of first examinations was realized in 21 week, control and interstitial fibrosis. Epithelial to mesenchymal transition (EMT) is a key molecular examinations after 30 week of pregnancy. There were found 239 pathological findings i.e. mechanism leading to myofibroblast accumulation in renal fibrosis. We investigated the 35.9% of all cases. Most frequently were detected urinary tract abnormalities such as interplay of macrophage infiltration, chemokine production, and EMT in renal fibrosis urinary tract obstructions /ureteropelvic junction obstruction, posterior urethral valve, induced by unilateral ureteral obstruction (UUO). Methods. Newborn mice (C57BL6) were megaureter/, cystic kidney /most frequently unilateral multicystic renal dysplasia/ subjected to complete unilateral ureteral obstruction (UUO) or sham operation at the second and bilateral renal agenesis. 62 children with a confirmed abnormality were treated day of life, and were sacrificed 1, 5 or 12 days later. BX 471, a CCR-1 antagonist, was surgically postnatally. injected s.c. at 100 mg/kg/BW per day (d2-d14). Kidney sections were stained for After discussions with pregnant mother and her family, the pregnancy was terminated by macrophages, lymphocytes, apoptosis, tubular atrophy and interstitial fibrosis. RT-PCR was artificial abortion in 40 cases, i.e. performed in UUO kidneys and controls for the EMT transcription factors snail and slug, in 16.7% of all pathological findings. The main reasons were bilateral renal agenesis, alpha-smooth muscle actin (sma) and vimentin. Results. EMT was rapidly induced within bilateral cystic dysplasia and renal anomalies associated with multiple malformations and 24 hrs after UUO with upregulation of snail and slug, preceding the induction of sma and chromosomal defects with poor prognosis. Prenatal findings and results of autopsy of the vimentin. In the presence of BX471, kidney chemokine, snail, and slug expression were fetus correlated in 97.5% cases. completely attenuated. This prevented tubular apoptosis (reduction by 73% (d5) and 32.5% Prenatal scans of all these abnormalities are shown. (d12)) and interstitial fibrosis (reduction by 38%, d5 and d12) in the developing kidney with Urinary tract abnormalities could be a cause of renal insufficiency in childhood.Prenatal UUO. Conclusion. CCR-1 antagonism may prove beneficial in neonatal UUO, reducing diagnosis of urinary tract abnormalities facilitates optimal postnatal care, including early leukocyte recruitment, EMT, and interstitial fibrosis (DFG La1257-2/2). surgical intervention for those abnormalities requiring immediate relief of obstruction. Also,there is possible to inform the parents on the expected poor postnatal prognosis in the most severe cases and let them to decide if to terminate the pregnancy. Pediatr Nephrol (2006) 21:1493–1635 1559

COD. PP 149 COD. PP 150 Differential regulation of renal developmental genes in neonatal and THE EVALUATION OF INFA NTS WITH CONGENITAL adult mice with unilateral ureteral obstruction (UUO) HYDRONEPHROSIS B Lange-Sperandio, M Knop, B Rodenbeck, M Hömme, S Weber, F Schaefer Department MK Gürgöze, HM Poyrazoðlu, R Düþünsel, Z Gündüz, Ý Dursun, M Küçükayd›n, Deniz of Pediatrics, University of Heidelberg, Germany Demirci Departments of Pediatric Nephrology, Pediatric Surgery and Urology, Erciyes University of Heidelberg , Department of Pediatrics , 69120 Heidelberg , Germany University Faculty of Medicine, Kayseri, TURKEY , Departments of Pediatric Nephrology, Erciyes University Faculty of Medicine, Kayseri, Background. Congenital obstructive nephropathy interferes with normal renal development. TURKEY , 38119 Kayseri , Turkey Compensatory growth of the contralateral, intact opposite kidney is dependent on the severity and the duration of obstruction. We investigated the regulation of renal developmental genes in obstructed and contralateral kidneys of neonatal and adult mice Hydronephrosis is defined as dilatation of the renal pelvis and/or calyces. With the with unilateral ureteral obstruction (UUO). Methods. Newborn (2nd day of life) and adult increasing use of antenatal ultrasound, hydronephrosis has been reported more frequently. C57BL/6 mice (7-8 weeks of age) were subjected to complete UUO or sham-operation, and The aim of this retrospective study is to evaluate the outcomes of infants with congenital were sacrificed 1, 5, 12 and 19 days later. Quantitative real time RT-PCR was performed in hydronephrosis. On admission and at the end of study, glomerular filtration rates (GFR) in obstructed, intact opposite kidneys and controls for Gdnf, Six2, Six4, BMP4, HNF-1ß, all patients were estimated by using Schwartz formula. The relationship between GFR and Pax2, Eya1, and Dach1. Protein abundance was analyzed using Western blot. Results. other parameters were investigated. We evaluated 76 kidney units (56 infants) with Neonatal UUO induced an early upregulation with Gdnf (11-fold mRNA increase above hydronephrosis who were followed. The mean age was 67,6±89,6 days (range 1-330). The sham-operated control at d1) > Six2 (7.2-fold) > Six4 (4.5-fold). Neonatal intact opposite mean duration of postnatal follow-up was 41,4±26,3 months (range 1-96). The most kidneys showed a parallel expression pattern with Gdnf (9.1-fold, d1) > Six2 (5.3-fold, d1) common cause of hydronephrosis was ureteropelvic junction obstruction (42,1%). Thirty > BMP4 (3.2-fold, d 5). By contrast, adult kidneys with UUO showed a late upregulation patients with hydronephrosis (63%) were diagnosed with prenatal ultrasound. Both on (d12-19) with Gdnf (16.7-fold above sham-operated control, d19) > Six2 (4.8-fold, d12) > admission and at the end of study, GFR was low in 8 patients according to age-matche d Eya1 (2.7-fold, d19). Gene expression in intact opposite kidneys of adult mice was weaker values. In addition, twenty patients who had normal GFR on admission had low GFR levels with only transient upregulation of Pax2 (1.8-fold, d5). Conclusion: Gene regulation differs at the end of study. The frequency of urinary tract infection was higher in patients with low in neonatal and adult mice with UUO. Regeneration and repair may involve different genes GFR levels. There were significantly negative correlations between the level of GFR at the in developing and adult kidneys with obstruction (DFG La 1257/2-2). end of study and degree of hydronephrosis, serum creatinine levels, and presence of hypertension. In conclusion, the degree of hydronephrosis and serum creatinine levels on admission, and presence of hypertension on follow-up were determined as the most important prognostic factors in our study group.

COD. PP 151 COD. PP 152 Detection of renal tubular impairment in children with hydronephrosis KIDNEY AND BLADDER FUNCTION IN BOYS WITH POSTERIOR S Skalova(1), P Rejtar(2), S Kutilek (3) Depärtment of Paediatrics(1),Department of URETHRAL VALVE. Radiology(2), Medical Faculty Teaching Hospital, Hradec Kralove, Center of Clinical and Michaù Maternik, Aleksandra Ýurowska , Piotr Czarniak, Magdalena Drozynska-Duklas, Basic Research(3), Pardubice, Czech Republic Wojciech Kosiak, Andrzej Go ùæbiewski, Leszek Komasara Medical Faculty Teaching Hospital , Department of Paediatrics , 500 05 Hradec Králové , Medical University of Gdansk , Department of Pediatric Nephrology , 80-286 Gdansk , Czech Republic Poland

Purpose: As N-acetyl-beta-D-glucosaminidase (U-NAG) activity is considered a very A varied incidence of both decreased renal function and poor bladder function has been sensitive marker of renal tubular impairment, the aim was to measure U-NAG in children reported in boys with posterior urethral valve in spite of early valve ablation. with hydronephrosis and to look for relationship among selected clinical parameters. Aim of the study: To evaluate the frequency of chronic renal disease and bladder function in Materials and Methods: 31 children. (22 boys and 9 girls, mean age 2.3 ± 2.5 years) with boys born with PUV. hydronephrosis grade 1-4 had urinary NAG/creatinine ratio measured. In 18 patients the Materials and methods: A cross-sectional analysis was performed in a group of 59 boys hydronephrosis was unilateral, grade 1-4 (mean 3.1 ± 0.8), and in 13 patients, the aged 1-23 years (mean 9 years) with PUV. The presence of chronic renal disease (CRD) hydronephrosis was bilateral, grade 1-4 (mean 2.9 ± 0.7). In the patients with bilateral was assessed by renal ultrasound and estimation of glomerular filtration rate (GFR), hydronephrosis and different grade on each side, the highest grade was taken into Schwartz method and evaluation of serum cystatin c. Chronic renal disease was defined consideration. Therefore, the diagnostic distribution was as follows: grade 1, n = 1; grade 2, according to NFK K/DOQI Guidelines and classified into 5 stages. Evaluation of bladder n = 2; grade 3, n = 16; grade 4, n = 12. The patients with hydronephrosis grade 1-3 were function was based on bladder diary and urodynamic examination. Disturbances of bladder managed conservatively, while the children with grade 4 were confined to surgical function was evaluated according to International Children`s Continence Society (ICCS) treatment. terminology. Results: The U-NAG/Cr was significantly higher in the patients with hydronephrosis Results: 43 patients (73%) with PUV had different stages of chronic renal disease (Table 1). compared to reference data (p = 0.002). There was no difference in U-NAG/Cr between Different types of bladder dysfunction were observed in 42 boys with PUV(71%). (Table 2) children with unilateral and bilateral hydronephrosis (p= 0.51). There was no significant Conclusions: The vast majority of boys with PUV demonstrate symptoms of both chronic difference in U-NAG/Cr between children with grades 1-3 (pooled data) and grade 4, renal disease(73%) and bladder dysfunction (71%). respectively (p=0.89). There was no correlation between U-NAG/Cr and the grade of PUV patients require regular nephrologic and urologic assessment and control throughout hydronephrosis (r = 0.01). childhood. Conclusions: U-NAG/Cr is increased in children with hydronephrosis grade 1-4, however there is no relationship with the grade of hydronephrosis or with the amount of affected renal tissue. U-NAG/Cr is a useful marker of renal tubular impairment, however its relationship with the degree of kidney damage in patients with hydronephrosis should be considered as doubtful. 1560 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 153 COD. PP 154 Prognostic factors in Posterior urethral valves Clinical and molecular markers of chronic interstitial nephropathy in K McKeever ( presenting author ), J M Savage congenital unilateral ureteropelvic junction obstruction (UPJO) , 8a WALKER`S FARM , BT26 6RQ HILLSBOROUGH , CO DOWN U K L Murer(1-2), E Benetti(1), S Centi(2), M Della Vella(2), L Artifoni(2), A Capizzi(4), P Zucchetta(3), D Del Prete(5), C Carasi(1), G Montini(1), W Rigamonti(4), G Zacchello(1). Objective: to determine the significance of different prognostic factors on long-term renal (1)Nephrology, Dialysis and Transplant Unit, Department of Pediatrics, Univ. of Padua, (2) function in boys with posterior urethral valves (PUVs) Laboratory of Pediatric Nephrology, Department of Pediatrics, Univ.of Padua (3)Nuclear Medicine, Department of Diagnostic Medical Sciences, Univ.of Padua (4)Department of Method: A total of 32 cases of PUVs from 1995-2003 were identified in Northern Ireland. Urology, Section of Pediatric Urology, Univ.of Padua (5)Department of Medical and The mean follow up time was 6.7years. Chronic renal impairment (CRI) was defined as a Surgical Sciences, Laboratory of Molecular Biology, Univ. of Padua GFR of less than 80ml/min/1.73m2. Department of Pediatrics - University of Padua , Via Giustiniani 3 , 35128 Padua , Italy The population was divided into 2 groups. Group1 had normal renal function ( RF) at most recent follow up while group 2 had CRI. Groups were compared for age at presentation, Purpose. To evaluate clinical and biological variables and their meaning as reliable markers renal function after 5 days catheter drainage and during follow-up, presence of a non- of chronic interstitial nephropathy in a selected group of children with antenatally detected functioning kidney,Vesico-ureteric Reflux ( VUR), DMSA findings and final patient age. hydronephrosis, who underwent pyeloplasty because of congenital unilateral UPJO. Materials and methods. We compared pre- and postnatal ultrasonographic records and pre- Results: There were eleven ( 34.3%) patients in Group 2 ( CRI) at most recent follow up operative scintigraphic data of two groups of children, divided according to the absence ( mean 8.22 years, 2-10.6 years ) . These patients had a significantly higher serum creatinine (group1) or presence (group 2) of chronic interstitial nephropathy in renal biopsy. after 5 days catheter drainage (mean 186, p<0.04, size effect 0.296), and at age 1 year Tubulointerstitial immunostaining for vimentin and a-smooth muscle actin (aSMA) and the ( mean 165, p<0.04, size effect 0.135). The presence of a non-functioning kidney ( p< 0.03) immunohistochemical and mRNA expression of the Renin Angiotensin System peptides was also a significant prognostic factor for abnormal RF. Other variables showed no and TGFb1 were evaluated. statistically significant differences ( Ante-natal v post-natal diagnosis; early v late Results. Twentyseven children were enrolled. Group 2 patients were significantly younger diagnosis, VUR, DMSA findings; serum creatinine at 2 years of age ; serum creatinine > 70 at the prenatal diagnosis (p=0.031), had lower split renal function (p=0.005) and worse umol/l at age 1; age at most recent follow up ). drainage (p=0.035) in pre-operative diuretic renography. No differences were found in terms of hydronephrosis degree or its pre- and postnatal variation. Group 2 biopsies showed Conclusions: The most significant prognostic factor for the future development of chronic greater immunostaining for aSMA and vimentin (p=0.004 and p=0.047, respectively) and renal impairment is the serum creatinine after 5 days of catheter drainage TGFb1 mRNA levels (p=0.06). Vimentin and aSMA positivity correlated with renin, AT1, AT2 and TGFb1 mRNA levels, and all correlated with pre-operative split renal function and post-micturition washout. Renal function did not improve significantly in group 2 at post- operative renography. Conclusions. In congenital unilateral UPJO, chronic interstitial nephropathy and post- operative poor recovery seems to be associated with an earlier diagnosis of hydronephrosis, a functional loss greater than 10% and a worse scintigraphic drainage. Moreover, we observed a strong correlation between the molecular fibrogenetic markers and both histologically and scintigraphically proven renal damage.

COD. PP 155 COD. PP 156 Primary non-refluxing megaureter: the expectant attitude. INFLUENCE OF MAG-3 ON OBSTRUCTIVE AND NON- M C Ribeiro, M J Silva, C Miguel, P Teixeira Pediatrics Department - Hospital S. João de OBSTRUCTIVE DILATATIONS IN THE EVALUATON OF Deus, S.A. – Vila Nova de Famalicão. Portugal. ANTENATAL HYDRONEPHROSIS , Rua António Patricio 104 R/C esq , 4460-204 Sra da Matosinhos , Portugal Kasap B, Soylu A, Erdur B, Türkmen M, Durak H, Kavukcu S , CamliCay Mah. 5182 Sk. No:112/A Urla , 35315 Izmi r , Turkey Introduction: The treatment of primary non-refluxing megaureter (PNRM) has been object of controversy. In case of recurrent infection or obstructive uropathy, the need for surgery is We aimed to determine the utility of MAG-3 in obstructive and non-obstructive dilatations obvious. In other cases the vigilant attitude is frequently the option. during evaluation of antenatal hydronephrosis (AH). Aim: Evaluate complications in our outpatient population with the diagnosis of PNRM. Material and Methods: We studied fourteen patients. Variables: gender, age at diagnosis, The data of patients with AH were evaluated retrospectively. The first postnatal US was presentation, family history of renal disease, echography and isotopic renogram findings, performed in the third day of life, MCUG at the first month and MAG-3 in the suspicion of associated malformations, complications, follow-up time. obstruction (absence of VUR or progression in hydronephrosis despite VUR). Gestational Results: Nine patients (64%) were boys and eight (57%) had prenatal diagnosis of renal weight (GW) at diagnosis, postnatal US, MCUG and MAG-3 findings, medical history for disease. Others were diagnosed after urinary tract infection (3) or other motives (3). The left surgical interventions (SI) or UTI and follow-up durations were recorded. US findings were ureter was implicated in 43% (6) and both ureters in 21% (3). Medium dimensions of grouped as GroupA (grades0-1) and GroupB (grades2-4). MAG-3 findings were grouped as megaureter were 7.8 mm on the left and 10.5 mm on the right. We found ipsilaterally two Group1 (non-obstructive dilatations) and Group2 (obstructive dilatations).The parameters ureteroceles and one ectopic ureter and contralaterally one case of grade I vesico-ureteral were compared between the groups. reflux and one multicystic kidney. In the initial renogram only one patient had obstructed urinary tract needing surgery. All patients had prophylactic antibiotics. Medium follow–up Forty-four patients (M/F:38/6) with AH were followed up for 13.210.3(2-40) months. US time was 37.8 months. Four patients (28%) were discharged after normal renogram and and MCUG (VUR:13 patients) were performed in all patients, while MAG-3 was performed imaging, 57% (8) are still in follow-up (3 of which developed marked hydronephrosis with only in 33 of them. None of the patients with GroupA US findings had a MAG-3 finding deteriorating renal function needing surgery). Two patients (14%) were lost on follow-up. requiring SI. When US findings were compared between Groups 1(n:9) and 2(n:22), Discussion: We found 14% of contralateral pathology which substantiates the need for a GroupA findings were more frequent in Group1 (89% vs. 28%;p:0.00). SI was more careful initial approach to these patients. Conservative attitude is appropriate for those with frequent but not significant in Group 2 (45.5% vs. 11.1%; p:0.07), spontaneous regression normal renal function and drainage, although close follow-up is needed for early detection was more frequent in Group1 (78% vs. 27%;0.01) and UTI ratios were similar between the of renal function deterioration. groups (p:0.54).

The risk of SI and UTI is more frequent and the chance of spontaneous regression is lower in obstructive dilatations. Thus, MAG-3 that can provide this differentiation is useful in patients with AH for deciding SI and for clinical follow-up. Pediatr Nephrol (2006) 21:1493–1635 1561

COD. PP 157 COD. PP 158 Serial ultrasound is a good predictor of kidney damage in children with MULTIDISCIPLINARY APPROACH TO PRENATAL congenital hydronephrosis HYDRONEPHROSIS P Geier (1), O Smakal (2), K Michalkova (3), T Tichy (4), H Flogelova (1) Depts of A G Güven, S Akman, M Melikoðlu, G Karagüzel, E Güntekin,E Kukul, A Kabaalioðlu, E Pediatrics (1), Urology (2), Radiology (3), Pathology (4), Teaching Hospital, Palacky Alimoðlu, F Ayd›n, F Güngör University, Olomouc, Czech Republic , Akdeniz University, Medical Faculty, Department of Pediatric Nephrology , 07070 , Dept of Pediatrics, IP Pavlova 6 , 775 20 Olomouc , Czech Republic antalya , Turkey

In most children with congenital hydronephrosis, the urine outflow impairment is transient Objectives: To evaluate the usefulness of an algorithm for the follow up of infants with and spontaneous remision occurs with time. The obstruction is present only in a minor prenatal hydronephrosis. group of children, and if untreated, might lead to renal parenchyme damage. Early detection Methods: An algorithm was developed by our pediatric urology team (nephrologist, of renal parenchyme damage is important, but very difficult at the same time. surgeon, urologist, radiolog, nuclear medicinist). In this algorithm, according to the antero- The aim of our study was to find out, whether there is correlation of ultrasound findings and posterior diameter of renal pelvis on renal ultrasonography at the first week of life, MAG 3 the degree of renal parenchyme damage. scintigraphy was performed or not. Methods: A wedge renal biopsy was obtained from 50 infants, who underwent surgery Nephrostomy or early nephrectomy was selected according to the antero-posterior diameter because of hydronephrosis in the time period 2000-2003. The histological findings were of renal pelvis and differential renal function (DRF); otherwise patients were under periodic classified according to Zhang. Patients with normal histological findings created group A. follow up (ultrasonography, Tc 99m DTPA scintigraphy, voiding cystourethrography i f Group B created patients with more or less serious renal parenchyme damage necessary). Surgical intervention was introduced based on ultrasonographic progression of (glomerulosclerosis, tubulointerstitial fibrosis). Prior to surgery, all children were examined hydronephrosis in addition to reduction of DRF. by diuretic renography and serial ultrasound. Renal pelvis diameter and renal parenchymal Results: 71 infants (16 girls, 55 boys) were included in this study. Patients were followed thickness were measured. according to the algorithm and results were evaluated retrospectively. Results: In our group of 50children, 33 had normal split renal function on diuretic Diagnostic distrubition: Ureteropelvic junction (UPJ) obstruction in 27(38%), non- renography. 20 of them had renal damage on histology (group B), 13 had normal histology obstructive hydronephrosis in 32%, vesico-ureteral reflux in 7%, multycystic dysplastic (group A). 19 children of group B had serious hydronephrosis on ultrasound examination kidney in 6%, uretero-vesical junction obstruction 4%, double collecting system 4%, others (parenchymal thickness 3mm or less) or progression of hydronephrosis on repeated 9% (including posterior urethral valve in 3). examination while among 13 children in group A only 4 had serious hydronephrosis on 55% of infants were managed conservatively. Nephrectomy in 7% in all patients, ultrasound or progression during follow up ( p 0,01). pyeloplasty in 17/27 patients with UPJ obstruction were performed. In conservatively Conclusion: Our study showed that progression of US findings during follow up is a good treated patients with UPJ obstruction, initial DRF was 46±8%, it was 51±12% at the end of predictor of renal damage in children with congenital hydronephrosis. the study. In pyeloplasty group, ipsilateral DRF were 35±13%, 49±14%, before and after surgery, respectively. Conclusion: Our algoritm could be safely used in conservatively follow-up of patients with prenatal hydronephrosis and of patients with UPJ obstruction requiring pyeloplasty.

COD. PP 159 COD. PP 160 Congenital Nephrosis, Mesangial Sclerosis, and Distinct Eye CHRONICALLY REDUCED GLOMERULAR FILTRATION RATE Abnormalities in a Newborn: Molecular Confirmation of Pierson IN PATIENTS WITH CLIN ICAL AND MOLECULAR WELL Syndrome. DEFINED DIAGNOSIS OF BARTTER SYNDROMES K Blahova (presenting author) M Zenker M Tesaøová J Stejska J Malec J Janda A Bettinelli*(Presenting Author), N Borsa**, E Puricelli°°*, C Mattiello**, F Emma^, M G Pediatric Clinic and 2nd Faculty of Medicine, Charles University, Prague , V Uvalu 84 , Bianchetti°, and Collaborative Italian Group of Bartter syndromes. Department of Pediatrics 15006 Prague 5 Motol , Czech Republic of *Merate (Italy) and °Bellinzona (Switzerland); **Laboratory of Molecular Biology, IRCSS Policlinico, Milan; Departments of °°Pediatrics, University of Insubria, Varese and Introduction: Demonstration of a newborn with congenital nephrosis, mesangial sclerosis, ^Pediatric Nephrology, Bambino Gesù Hospital, Rome (Italy). eye abnormalities. Department of Pediatrics , Mandic Hospital , 23807 Merate , Lecco Italy Patient: A boy from 2nd pregnancy (spontaneous abort previously) of unrelated parents, born at 34 weeks of gestation (2 900g/49 cm) with oedemas, respiratory distress, oliguria, Background eye abnormalities (unilateral buphtalmos/microphtalmos, cataracts, corneal and retinal Anecdotal, mostly poorly documented reports suggest that patients with Bartter syndromes irregularities). Oligohydramnion and enlarged placenta (1.2 kg) were described. During 11 sometimes tend to a chronically decreased glomerular filtration rate. days the serum creatinine increased to 278 umol/L, urea to 8.4 mmol/L. Proteinuria (8.6 Study design g/L), hypoproteinemia (33.5 g/L) and hypoalbuminemia (15.7 g/L) were present. Renal Glomerular filtration rate, predicted by the Schwartz equation, was assessed in patients with biopsy and molecular investigation of family were indicated. He died at the age of 24 days Bartter syndromes (normal blood pressure, plasma potassium < 3.5 mmol/l, plasma from cardiorespiratory failure. bicarbonate > 28 mmol/L, and hyperreninemia) and homozygous or compound Methods: All known coding exons including the flanking introns of the LAMB2 gene were heterozygous mutations in one of the corresponding genes. amplified by PCR using an AB13730 automated sequencer (Applied Biosystems). Standard Results examination of renal biopsy, in addition immunohistochemical staining with laminin Ab-2 A total of 36 patients satisfied the inclusion criteria. The follow-up period ranged from 2 to antibody (Neomarkers Laminin Ab-2). 23, median 9 years. Glomerular filtration rate was less than 75 ml/[min. 1.73 m2] in 7 of the Results: The patient turned out to be compound-heterozygous for two small deletions in 36 patients (ranges: 40 to 73, median 67 ml/[min. 1.73 m2]). They were 1 of the 10 patients exon 14 ( c.1875-1879delGCGCT - L625fsX629) and exon 27 (c.4504delA- with mutations in SLC12A1 gene (= Bartter type I), 4 of the 19 patients with mutations in R1502fsX1519), the exon 14 mutation was iherited from mother, the exon 27 mutation from the CLCNKB gene (= Bartter type III) and both patients with Bartter syndrome associated father. Renal biopsy findings: segmental and global sclerosis, simple capillary tuft with fetal with neurosensorial deafness and mutations in BSND gene (= Bartter type IV). The type of podycytes, tubular atrophy, displayed interruped linear positivity of glomerular and glomerular filtration rate was normal in 5 patients with mutations in the KCNJ1 gene (= tubular basement membranes (lamininAb-2 antibody staining). Bartter type II). Conclusion: These findings confirmed an autosomal-recessively inherited Pierson sy. Pathological proteinuria developed during the follow-up period in 4 patients and severe Parents molecular investigation will offer prenatal diagnosis in future. dehydration had been reported in 2 newborns. Conclusions Patients with biallelic mutations in Bartter syndrome genes rather often (19.4%) tend to develop on follow up a pathologically reduced glomerular filtration rate. It is tempting to assume that some of them might progress to end stage kidney disease disease. 1562 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 161 COD. PP 162 CLINICAL AND GENETIC STUDIES OF THE 44 FAMILIES WITH Alterations in pre-mRNA splicing of the ClC-5 gene in patients with POLYCYSTIC KIDNEY DISEASE Dent’s disease E F Andreeva, A A Kozareva, N D Savenkova, V I Larionova F Claverie-Martín (1), E Ramos-Trujillo (1), M C Vega-Hernández (1), P Tejera (1), F J St.-Petersburg State Pediatric Medical Academy , 2, Lytovskaya, Department o f González-Paredes (1), V García-Nieto (2) Unidad de Investigación (1), Unidad de Paediatrics , 194100 Saint-Petersburg , Russia Nefrología Pediátrica (2), Hospital Universitario N. S. de Candelaria, Santa Cruz de Tenerife, Spain Recent studies show link between G-protein and PKD [Arnaout M.A., 2001; Nauli S.M. et Hospital Universitario N. S. de Candelaria , Unidad de Investigación , 38010 Santa Cruz de all, 2003]. Tenerife , Spain Hereby we report about 44 families, which contain 47 children with PKD (26 boys, 21 girls), in age range from 3 months till 18 years. The analysis of the family histories revealed Dent’s disease is a renal tubulopathy characterized by low-molecular-weight proteinuria, ADPKD in 27, ARPKD in 6 and nondifferential PKD in 14 children. Clear majority among hypercalciuria, nephrocalcinosis and nephrolithiasis. Mutations in CLCN5, the gene the children with ADPKD and ARPKD were represented by girls. encoding the Cl-/H+ exchange transporter ClC-5, cause this disease. We have identified Most frequently (80%) abdominal pain syndrome accompanies with ADPKD. Probably, it several new mutations in the CLCN5 gene of Spanish patients with Dent’s disease. The aim is due to relatively large size of cysts (sized up to 5,8sm) caused by ADPKD. Among 47 of this study was to analyze the effect of two exonic mutations and one splice site mutation children, 22 (47%) had arterial hypertension, 33 (70%) pyelonephritis, 40 (85%) in CLCN5 pre-mRNA splicing. We also examined the molecular mechanisms responsible proteinuria, 27 (57%) hematuria. for exon 11 skipping in a previously described Alu insertion mutation of this gene. Chronic renal failure was developed in 7 (15%) children. Two of them had ADPKD, 5 CLCN5 minigenes were constructed in the Exontrap cloning vector. Modifications were ARPKD. One (2% of all children) with neonatal form of ARPKD died. introduced by site-directed mutagenesis and confirmed by DNA sequencing. RNA samples Molecular genetic research was carried on 28 families with PKD, which contain 40 children isolated from blood and transfected COS7 cells were analyzed by RT-PCR. and 38 parents. Among them, 15 families had ADPKD, 5 were with ARPKD, and other 8 – The RNA analysis showed that mutation IVS2-2A>G resulted in loss of exon 3 in the with nondifferential PKD. CLCN5 mRNA, while mutation W547G altered the expression of two alternative splice We detected genotypes and alleles distribution C825T GNB3 by PCR with restriction assay forms. One of these mRNAs lacked exons 10 and 11. Both exon skipping events changed among probands. Genotype distribution among ADPKD (19) was TT-10,5%, CT-42,1%, the open reading frame introducing a premature stop codon. Re-establishment of specific CC-47,4%, among ARPKD (5) was only CT-100% and among nondifferent heredity o f exonic splicing enhancers (ESEs) in exon 11-Alu promoted its incorporation in the mRNA. PKD (6) was TT-16,7%, CT-66,6%, CC-16,7%. Our results indicate that missense mutations in the CLCN5 gene can also disrupt splicing. Conclusion. Ñlinical and genealogical heterogeneity of PKD has been detected. It is The exon skipping produced by the Alu insertion in exon 11 was due to the interruption of proposed that this C825T polymorphism GNB3 may influence in different types PKD an ESE, although we can not exclude the possibility of splicing inhibitory sequences in the formation. Alu element. This work was supported by grant PI042620 from Fondo de Inversión Sanitaria.

COD. PP 163 COD. PP 164 URINARY TGF-BETA1 CONCENTRAT ION IN CHILDREN WITH A NEW NEPHRONOPHTHISIS PROTEIN, NEPHROCYSTIN-6, RENAL POLYCYSTIC DISEASES INTERACTS WITH RPIP8 AND FLJ13231 GENE PRODUCTS IN A Biernacka, W Zoch-Zwierz, A Wasilewska, A Puczko-Michalczuk, K Zwierz YEAST-TWO-HYBRID SCREENING I Department of Paediatrics, Medical University in Biaùystok, Poland , Waszyngtona 17 , M Attanasio1, JA Sayer1, E Otto1, JF O’Tool e1, J Helou1, F Hildebrandt1 1Departments of 15-274 Biaùystok , Poland Pediatrics and Human Genetics, University of Michigan, Ann Arbor MI, USA University of Michigan , 1150 west medical center drive , 48105 Ann Arbor , MI USA Autosomal dominant polycystic disease is characterised by abnormal polycystin, protein, which is a component of basement membrane and extracellular matrix. Nephronophthisis (NPHP) is an autosomal-recessive cystic kidney disease and represents Transforming growth factor (TGF-beta1) is a cytokine, which takes part in development of the most frequent genetic cause of end-stage renal failure in the first 3 decades of life. (1) renal tubule epithelium and stimulates the synthesis of extracellular matrix proteins. Nephrocystin-6, the gene mutated in nephronophthisis with neurologic involvement, has The aim of work was the assessment of TGF-beta1 concentration in children with renal recently been identified by positional cloning (2). Since nearly 60% of nephronophthisis polycystic disease. Material and methods: The examined group (I) consisted of 33 children cases are still not explained, we sought nephrocystin-6 interaction partners as candidates for aged (median 14.7 years, range 4.0-17.9): A – 11 children with solitary cyst, II – 22 with other NPHP related genes, using yeast-2-hybrid library screening. polycystic renal disease. Control group (C) consisted of 20 healthy children at the same age. Nephrocystin-6 is a novel protein subcellularly localized at the centrosome as NPHP1, The concentration of urinary TGF-beta1 was measured using immunoenzymatic ELISA NPHP2 and other proteins defective in cystic kidney diseases (3). method. The results showed that mean concentration of urinary TGF-beta1 (121.9 ± 168 Two nephrocystin-6 partial length clones were used, JAS1 (aa 1-789) and JAS2 (aa 1953- pg/mg cr.) was lower than in group B, in which it was 207.2 ± 361 pg/mg cr.. However the stop). Transcripts were subcloned into the pDEST32 vector as bait. Yeast-two-hybrid difference was not statistically significant (p>0.05).In both subgroups (A and B) urinary analysis was performed using the ProQuest™ Pre-Made cDNA Libraries (Invitrogen) as a excretion of TGF-beta1 was higher than in control group (C) (p<0.05). In 4 (36%) children prey. Positive clones indicating interaction with nephrocystin-6 were confirmed by from group A and 8 (36%) from group B the urinary concentration of TGF-beta1 was below subcloning into pDEST22 and pDEST32 and by performing reciprocal bait/prey and the sensitivity of the method. No correlation between TGF-beta1 and children’s age, urinary prey/bait direct interaction assays by growth on selection plates. osmolality and GRF according to Schwartz was found. It was a positive correlation between The products of genes RPIP8 and of the FLJ12321 interacted with nephrocystin-6 both as urinary TGF-beta1 concentration and total diameter of renal cysts. preys that as baits with JAS1 and JAS2 respectively. Conclusions: TGF-beta1 takes part in renal cyst formation and increased urinary excretion RPIP8, a guanine nucleotide exchange factor, specifically activates the member of RAS of TGF-beta1 in proportion to the dimension of renal cysts may be an evidence of that fact. oncogene family Rap2, which is possibly involved in cytoskeletal reorganization. FLJ12321 codes for HCAA (Hepatocellular Carcinoma Associated Antigen), a protein of unknown function expressed in hepatocellular carcinoma cells.

1) Hildebrandt F et al. Clin Investig 70:802-808, 1992 2) Sayer JA et al. Nat Genet, in press. 3) Hildebrandt F et al Nat Rev Genet 6:928-40, 2005 Pediatr Nephrol (2006) 21:1493–1635 1563

COD. PP 165 COD. PP 166 Phenotype and genotype analysis of Dent disease and Lowe syndrome Halitosis due to cysteamine administration in cystinosis patients is HI Cheong*(1), HY Cho(1), CG Lee(2), IS Ha(1), Y Choi(1) Department of Pediatrics, caused by dimethylsulfide Seoul National University Children’s Hospital(1) Department of Pediatrics, Ilsan Paik MTP Besouw, HJ Blom, A Tangerman, EN Levtchenko E Levtchenko Hospital(2) Presenting author* University Medical Center Nijmegen , Dept Pediatric Nephrology, POB 9101, 6500 HB , Department of Pediatrics, Seoul National University Children`s Hospital , 28 Yongon- 6500 HB Nijmegen , The Netherlands The Netherlands Dong, Chongro-Gu , 110-744 Seoul , South Korea Background: Cystinosis is a rare autosomal recessive disorder characterized by Dent disease is caused by mutations of CLCN5 in most cases. However, recently, some intralysosomal cystine accumulation. Cysteamine removes cystine from the lysosomes and Dent patients with OCRL1 mutations have been detected. OCRL1 is originally known to be slows down the progression of the disease. Bad breath odour (halitosis) caused by the defective gene in Lowe syndrome. cysteamine hampers the compliance with cysteamine treatment. The aim of this study was In this study, the mutational analyses of both genes and genotype-phenotype correlations to investigate which cysteamine metabolites are responsible for halitosis in cystinosis were performed in 13 boys, who met the diagnostic criteria for Dent disease (low molecular patients. weight proteinuria, hypercalciuria and nephrocalcinosis) and 11 boys with Lowe syndrome Patients and methods: Four patients with cystinosis, aged 12-29 years were included. Blood, (proximal renal tubular acidosis, congenital cataract and developmental delay). expiration air and urine were taken prior and every 60’ during 360’ after the administration Eight different CLCN5 mutations were detected in 10 Dent patients (Group A), and three of 15 mg/kg cysteamine bitartrate (Cystagon®) for the determination of cysteamine and mutations in OCRL1 (F226S, Q260E and c.455delA) in 3 remaining patients (Group B). cysteamine metabolites by gas chromatography and HPLC. Among 11 Lowe patients, OCRL1 analysis was done in 5, and revealed 3 nonsense Results: Two metabolites of cysteamine causing halitosis were detected: methanethiol (MT) mutations and 2 abnormal splicings. and dimethylsulfide (DMS). Maximal concentration (Cmax, mean(SD)) of MT and DMS in Group B had more severe degree of tubular proteinuria (urinary â2-microglobulin, the expiration air were 1.77 (3.43) nmol/L and 20.04 (24.52) nmol/L respectively. DMS 43.9±21.6 vs 18.7±9.2 ug/mg creatinine, P = 0.053) and hypercalciuria (urinary concentrations over 0.5 nmol/L are known to cause halitosis. Urinary DMS was 643.1 calcium/creatinine, 1.91±1.38 vs 0.31±0.17, P = 0.011) than group A. One patient in group (394.7) nmol/6 hours, which is 0.07% of the amount excreted via expiration. In time, Cmax B with c.455delA had mild degree of uricosuria and borderline developmental delay and of plasma cysteamine preceded Cmax of blood MT, which in their turn preceded Cmax of acidosis, which suggested that he had an incomplete and mild form of Lowe syndrome. blood DMS. These results suggest that there is a continuing spectrum of phenotype in patients with Significant positive correlations between plasma cysteamine, MT and DMS levels and CLCN5 or OCRL1 mutations. One end is classical Dent disease with CLCN5 mutations, blood - breath MT and DMS levels were observed. and the other end is full-blown Lowe syndrome with OCRL1 mutations. In the middle, Conclusion: Halitosis due to cysteamine administration in cystinosis patients is mainly there are isolated renal form (Dent variant) and incomplete or mild form of Lowe syndrome caused by DMS. Further research is required to develop agents reducing the odour of DMS, with OCRL1 mutations. which will enhance the compliance with cysteamine treatment.

COD. PP 167 COD. PP 168 CD2AP MUTATIONS IN PATI ENTS WITH IDIOPATHIC Exclusion of the uroplakins as candidate genes for muticystic dysplastic STEROID-RESISTANT FOCAL SEGMENTAL kidneys GLOMERULOSCLEROSIS (FSGS) SA Feather, D Jenkins, R Belk, M Bitner-Glindzicz, A Woolf, DFM Thomas M Lõwik (1), P Groenen (2), M Lilien (3), L Monnens (1) and L van den Heuvel (1) Dept of paediatric nephrology , Level 4 Gledhow Wing, St James`s University Hospital , Department of Pediatric Nephrology (1) and Pathology (2), Radboud University Nijmegen LS16 6AJ Leeds , West Yorkshire U K Medical Centre, and Department of Pediatric Nephrology (3), University Medical Centre Utrecht, The Netherlands Presenting author: B Van den Heuvel Uroplakins (UP) are proteins which coat the surface of the urothelium and mice which lack Radboud University Medical Center , Dept Pediatric Nephrology, POB 9101 , 6500 HB UP111a have increased urothelial permeability associated with congenital malformations of Nijmege Nijmegen , The Netherlands The Netherlands the renal tract and mice which lack UP11 mutations have congenital hydronephrosis. We have previously reported the association of de novo heterozygous mutations in UP111a in Mutations in several podocyte genes have been implicated in FSGS. Heterozygote patients with renal adysplasia, UP11 mutation in patient with primary vesicoureteric reflux mutations in CD2AP have been reported as cause of FSGS. The gene encoding CD2AP was (VUR) and reflux nephropathy and association between Pro154Ala polymorphism of investigated for the presence of mutations in a group of twenty pediatric idiopathic steroid- UP111a and VUR. resistant FSGS patients. Genomic DNA was isolated from blood leukocytes. Amplification of the CD2AP gene was performed by PCR using primers in the intron regions flanking the We hypothesized that UP mutations might be responsible for the genetics of multicystic exons. The PCR products were analysed by DNA sequencing. The functional consequence dysplastic kidneys (MDCK). Nineteen unrelated cases of MDCK, 18 sporadic and 1 of observed mutations was confirmed by an in vitro actin binding assay and CD2AP familial were studied. None of the patients had clinical evidence of features suggesting a expression on lymfocytes. multi-organ syndrome. Total genomic DNA extracted from lymphocytes of the patients was We observed one heterozygous mutation (c.1488G>A; p.M496I). In addition a homozygous directly sequenced using primers designed to amplify the exons of UP 1b, UP 11 and nonsense mutation (c.1834C>T; p.E612X) resulting in a premature stop codon was UP111a. No mutations were discovered in these genes in MDCK. observed in a second patient. Both mutations were not observed in 100 control alleles. To investigate whether the CD2AP mutations affect the interaction with actin we performed an Although UP mutations account for a proportion of patients with adysplasia and VUR UP in vitro actin binding assay. In vitro translated wildtype and mutant CD2AP proteins were 1b, UP11 and UP111a are not implicated in the genetics of MDCK. incubated with polymerized filamentous actin (F-actin). Evidence was obtained for a disturbed interaction of the mutated CD2AP with F-actin in the patient carrying the homozygous nonsense mutation. Finally, also an aberrant expression of CD2AP on the lymfocytes was observed in the latter patient.We report 2 novel mutations in de CD2AP gene in patients with idiopathic steroid-resistant FSGS. One of the mutations results in a disturbed interaction of the mutated CD2AP protein with F-actin and a reduced CD2AP expression on lymfocytes. 1564 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 169 COD. PP 170 A RECURRING MUTATION IN THE GITELMAN GENE OF Unilateral renal agenesis associated with 76th case of Coffin- Siris ITALIAN PATIENTS: IS TH ERE A COMMON ANCESTOR? syndrome in the world. M-L Syren, 1,2 N Borsa, 2 C Mattiello, 2 L Calò, 3 M Matterassi, 4 A Orrico, 5 G Vezzoli, AJ Al mosawi 6 A Bettinelli, 7 M Travi, 2 S Tedeschi, 2 1 Dept of Pediatrics and Neonatology, University University Hospital in al Kadhimiyia , Head of the department of pediatrics , 70025 of Milano, Milano 2 Lab.of Medical Genetics, IRCCS Fondazione Policlinico, Mangiagalli Baghdad , Iraq e Regina Elena, Milano 3 Dept of Clinical and Experimental Medicine, University of Padova, Padova 4 Dept. of Nephrology and Dialysis, Ospedale Pediatrico Meyer, Firenze 5 Background: Coffin Siris syndrome (CSS) is a rare clinical syndrome of unknown etiology, Dept of Molecular Medicine, University of Siena, Siena 6 Dept of Nephrology and Dialysis, first described by Coffin GS and Siris E in 3 unrelated girls with mental retardation and Ospedale di S.Raffaele, Milano 7 Pediatric Unit, Ospedale L. Mandic, Merate absent nails and terminal phalanx of the fifth finger in 1970.Untill now only 75 cases have Dept of Pediatrics and Neonatology , Dept of Pediatrics and Neonatology, via della been reported. Renal agenesis has been reported infrequently in CSS. Commenda, 9 , 20122 Milano , Italy Patient: A 4 years old dysmorphic and mentally retarded girl. She was born at 30 weeks o f gestation by cesarean delivery because of lack of progress of labour.Her weight was 1.75 Gitelman’s syndrome (GS) is one of the hereditary renal tubulopathies characterised by kg. During infancy feeding difficulties was prominent. Her development was retarded with hypokalemic metabolic alkalosis, hyperreninemia with normal or somewhat lower blood no language development, gross motor milestones was slightly better than other fields of pressure. Distinguishing features from the other forms [i.e. the Bartters’syndromes, (BS)] development. She didn’t have any urinary complaint. Her growth was retarded with all of are typically a later onset, hypomagnesemia and hypocalciuria concomitantly with her parameters below the third centiles.She has coarse facial features with thick eyebrows, normocalcemia. mild left ptosis big mouth ,thick prominent lips facial hypertrichosis and low nuchal hair GS is caused by inactivating mutations in the SLC12A3 gene encoding the thiazide- line. Her hands showed single palmer creases, fingers and nails were small; the terminal sensitive NaCl-cotransporter. phalanges of her fingers were small with hypoplastic changes more severe on the little In our cohort of patients with a clinical and molecular diagnosis of GS we found 66 finger of the right hand. Radiological examination showed hypoplastic distal phalanges with mutations distributed between missense, nonsense, insertions and deletion mutations. They rudimentary terminal phalanx of the right fifth digit. Abdominal sonography revealed are spread along the gene without any hot spot. Only few mutations recur that were also absence the right kidney with no other abnormality. Brain CT scan and chromosomal identified in other countries. analysis showed normal finding.CSS has been reported from USA, Europe, Turkey, Japan, In the Italian GS patients, especially one mutation, Ins7bp1227_1228, seems relatively and India. common. This insertion of 7 bp in exon 10 was found in ten unrelated alleles. Conclusion: 76th patient with CSS, and the first Arab with CSS, associated unilateral renal We characterised these subjects, except one which was not available, by extensive agenesis, an infrequently reported association. genotyping with polymorphic markers/SNPs flanking exon 10. A multiallelic polymorphism in intron 8 of the gene revealed 100% segregation of the 258 bp allele with the mutation even though this allele was found to be linked with wild type as well. Furthermore, a common haplotype closely linked to the mutation was demonstrated in all the patients and parents carrying the insertion. The geographic distribution of these patients is, at the moment, circumscribed to the northern regions of Italy. We hypothesize that this mutation might be the result of a founder effect originated in a common ancestor in the Italian population.

COD. PP 171 COD. PP 172 Hypercalciuria in patients with CLCN-5 mutations NPHS2 GENE MUTATIONS IN CH ILDREN WITH APPARENTLY M Ludwig, B Utsch, B Balluch, S Fründ, E Kuwertz-Bröking, A Bökenkamp SPORADIC NEPHROTIC SYNDROME IN SPAIN VU medical center , de Boelelaan 1117 , 1081 HV Amsterdam , The Netherlands A Urisarri (presenting author), G Ariceta, P Outeda, JL Fdez-Iglesias, B Valenciano, A Bao, M Gil, S Malaga, A Vallo, A Pena, A Rguez do Forno, M Ubetagoyena, V Garcia-Nieto, Objectives: Hypercalciuria is regarded a characteristic symptom of Dent’s disease (OMIM XM Lens Laboratorio de Investigacion de Nefrologia. Unidad de Nefrologia Pediatrica. 300009), an X-linked recessive tubulopathy characterized by low-molecular weight C.H.U. Santiago de Compostela. Spain proteinuria (LMWP), nephrocalcinosis/nephrolithiasis, and progressive renal failure due to CHU Santiago de Compostela , Laboratorio Investigacion Enfermedades Renales mutations in CLCN5 gene. Data from CLCN5 disruption models suggest that renal calcium Hereditarias. A Choupana s/n. , 15706 Santiago de Compostela , A Coruna Spain excretion is determined by the balance between the loss of 25-hydroxyvitamin D and the stimulation of 1,25-dihydroxyvitamin D synthesis by increased luminal parathormone delivery. As the presence of hypercalciuria plays a major role in the decision to test fo r An autosomal recessive steroid-resistant (SRNS) subtype is caused by mutations of NPHS2 CLCN5 mutations, the prevalence of hypercalciuria in patients with CLCN5 mutations was gene, encoding podocin. determined. Methods: Renal calcium excretion was assessed in 34 male patients with CLCN5 mutations, AIM: To establish the prevalence of NPHS2 mutations in apparently sporadic pediatric NS who had been referred because of LMWP and at least one other symptom of Dent’s disease. in Spain. Hypercalciuria was defined as renal calcium excretion >0.1 mmol/kg/d. Our data were compared with published series of CLCN5 positive patients identified by a systematic DESIGN: multicenter cross-sectional study literature search. Results: In seven of the 19 families studied, at least one affected male had normal calcium POPULATION: 83 patiente 18 years with non-familial idiopathic SN: 38(46%) SRNS, 45 excretion. Hypercalciuria was observed in 22 out of 31 patients (71%), compared to 85 out (54%) steroid-sensitive (SSNS). 9 young adults (18-35y) with primary SRNS also studied. of 90 (94.4%) in published series from Europe and North America and 74.4% from Japan. 25% of the European/North American patients, 45% of the Japanese and 41% in the present METHODS: mutational analysis series had only two of the four principal symptoms of Dent’s disease. Conclusion: CLCN5 analysis should be considered irrespective of the presence of RESULTS: Age at onset: SRNS: 2.5y (range: 0-14.8, 2 cases congenital NS); SSNS: 4.2y hypercalciuria if at least two symptoms of Dent’s disease are present in the patient or his (range 1.8-17.3). Immunosuppressors: SRNS: 70%(53% remission); SSNS: 66%(96% family. remission). Biopsy: SRNS (one 84%, two 22.5%): 45% MC, 37%FSGS, 10%DMP, 7% DMS; SSNS (one 42%, two 15%): 81% MC. ESKD: SRNS: 10 children(26%), in 4.1 years; SSNS: none. Mutational analysis: SRNS: 3 children (7.9%) homozygous or compound heterozygous state: 1st case: R229Q/E281A-congenital NS, FSGS and normal GFR after 2y-; 2nd case: R229Q/E310K-congenital NS, MC and normal GFR 12.5y later-; 3rd case: delG419/delG419- diagnosed at 3y, with FSGS and normal GFR. Patients’ parents were carriers in 2 families (one child was adopted). One adult with SRNS had a compound heterozygous NPHS2 state: R229Q/E310K-onset at 25y, FSGS and normal GFR, after 8.2y. 2 children (4%) had a single heterozygous state (R229Q, P20L). SSNS: 0% homozygous or compound heterozygous state; 3 (7%) single heterozygous state: R229Q.

CONCLUSIONS: 8% children with apparently non-familial SRNS in Spain, suffer an autosomal recessive disease caused by NPHS2 mutations. Phenotype was highly variable - podocin was responsible for both congenital NS and disease in young adults as well. NPHS2 mutations diagnosis is not justified in SSNS. Pediatr Nephrol (2006) 21:1493–1635 1565

COD. PP 173 COD. PP 174 Uroplakins are excluded as candidate genes for multicystic dysplastic RENAL MANIFESTATIONS OF FABRY DISEASE IN CHILDREN: kidneys DATA FROM FOS – THE FABRY OUTCOME SURVEY SA Feather 1 D Jenkins 2 R Belk 1 M Bitner-Glindzicz 2 A Woolf 2 DFM Thomas 1 1 G. Pintos-Morell1, A. Rodríguez-Palmero1, U. Ramaswami2, R. Parini3, G. Kalkum4, and Depts of Paediatric Nephrology and Urology, St James’s University Hospital, Leeds,UK, 2 M. Beck4, on behalf of the FOS investigators. 1. Dept. of Paediatrics, University Hospital Institute of Child Health London, UK. Germans Trias i Pujol, Badalona, Spain. 2. Dept. of Paediatrics, Addenbrookes Hospital, Dept of paediatric nephrology , Level 4 Gledhow Wing, St James`s University Hospital , Cambridge, UK. 3. Dept. of Paediatrics, University of Monza, Italy. 4. Dept. of Paediatrics, LS16 6AJ Leeds , West Yorkshire U K University of Mainz, Germany Hospital Germans Trias Pujol , Department of Paediatrics , 123 Badalona , Spain Uroplakins (UP) are proteins which coat the surface of the urothelium and mice which lack UP111a have increased urothelial permeability associated with congenital malformations of Fabry disease (FD) is an X-linked lysosomal storage disorder with multisystemic the renal tract and mice which lack UP11 mutations have congenital hydronephrosis. We manifestations due to á-galactosidase A deficiency. The early onset of FD in children has have previously reported the association of de novo heterozygous mutations in UP111a in recently been well documented, although the life-threatening complications seen in adult patients with renal adysplasia, UP11 mutation in patient with primary vesicoureteric reflux FD patients, such as renal failure, cardiomyopathy and strokes, are not seen in early (VUR) and reflux nephropathy and association between Pro154Ala polymorphism of childhood. UP111a and VUR. We hypothesized that UP mutations might be responsible for the genetics of multicystic Data from FOS, an international database of patients with FD, were analysed to assess the dysplastic kidneys (MCDK). Nineteen unrelated cases of MCDK, 18 sporadic and 1 level of renal involvement in children with FD. In October 2005, 134 patients under 18 familial were studied. None of the patients had clinical evidence of features suggesting a years of age were registered in FOS. Of the 74 girls, 26 (35%) were receiving enzyme multi-organ syndrome. Total genomic DNA extracted from lymphocytes of the patients was replacement therapy with agalsidase alfa, compared with 33 of the 60 boys (55%). Common directly sequenced using primers designed to amplify the exons of UP 1b, UP 11 and clinical manifestations included pain attacks, chronic pain, abdominal pain, hypohidrosis UP111a. No mutations were discovered in these genes in MCDK. and angiokeratomas. Renal manifestations were noted from an early age. Proteinuria was Although UP mutations account for a proportion of patients with adysplasia and VUR UP the most prevalent renal manifestation, seen in 14/70 girls and 6/57 boys. Microalbuminuria 1b, UP11 and UP111a are not implicated in the genetics of in this cohort of patients was reported for 8 girls and 5 boys, and was recorded from 4 years of age. Haematuria was MCDK. present in 7 girls and 1 boy. Estimated GFR (Schwartz equation) was below 90 ml/min/1.73 m2 in 18 girls and 16 boys. Diastolic blood pressure was above normal for height, age and gender in 8/49 boys and 12/56 girls.

In summary, renal manifestations may occur at an early age in children with FD, particularly microalbuminuria/proteinuria. In this study, such manifestations were observed from 4 years of age. A decrease in GFR and a tendency for increased blood pressure was also noted during adolescence.

COD. PP 175 COD. PP 176 PHENOTYPE-GENOTYPE CORRELATIONS IN A COHORT OF 72 Genetic investigation of autosomal recessive distal renal tubular FŒTUS WITH AUTOSOMAL RECESSIVE POLYCYSTIC KIDNEY acidosis: evidence for early sensorineural hearing loss associated with DISEASE (ARPKD) mutations in ATP6V0A4 gene E. Denamur1, A. Bourillon2, O. Pascaud1, B. Gerard1, A.L. Delezoide3, R. Bouvier4, M.C. Rosa Vargas-Poussou 1,2, Pascal Houillier 3, Nelly Le Potier 2, Laurence Strompf 2, Anne Gubler5, L. Michel-Calemard6, P. Missy7, I. Zaccaria7, H. Le Nagard7, C. Alberti7, C. Blanchard 3 Xavier Jeunemaître 2and the Consortium in primary tubulopathies study Loirat8. 1 Laboratoire de Biochimie Génétique, Hôpital Robert Debré, Paris. 2 Laboratoire 1Département de Pédiatrie Médicale CHU de Rouen. 2Département de Génétique et de de Biochimie B, Hôpital Bichat, Paris. 3 Service de Biologie du Développement, Hôpital 3Physiologie. Hôpital Européen Georges Pompidou. Paris Robert Debré, Paris. 4 Laboratoire d’Anatomie Pathologique, Hôpital Edouard Herriot, Département de Pédiatrie Médicale - Unité de Néphrologie. CHU de Rouen , 1, rue de Lyon. 5 INSERM U574, Hôpital Necker, Paris. 6 Laboratoire de Biochimie Endocrinienne Germont , 76031 Rouen , France et Moléculaire, Hôpital Debrousse, Lyon. 7 Unité d’Epidémiologie Clinique, Hôpital Robert Debré, Paris. 8 Service de Néphrologie, Hôpital Robert Debré, Paris. Mutations in the ATP6V1B1 and ATP6V0A4 genes, encoding subunits B1 and 4 of apical Hôpital Robert Debré , 48 bd Sérurier , 75019 Paris , France H+ ATPase, cause recessive forms of distal renal tubular acidosis (dRTA). ATP6V1B mutations have been associated with early sensorineural hearing loss (SNHL) whereas We analysed the correlation between the severity of renal and hepatic histological lesions ATP6V0A4 mutations are classically associated with either late-onset SNHL or normal and PKHD1 mutations in 72 cases of ARPKD detected prenatally (54 foetus (median hearing. We assessed the phenotype and genotype of 43 new kindreds with recessive dRTA, gestational age (GA) 28 w), 18 new-borns (median age at death :1 day). Renal lesions 20 of which were consanguineous. Homozygosity mapping for the consanguineous families severity was correlated with GA (e 30 w vs > 30 w : p = 0.04). Hepatic fibrosis also tended and age-at-onset of SNHL for sporadic cases were used to determine which gene to test to be more severe for GA > 30 w (NS). The 66 coding exons of PKHD1 were studied using first. The two genes were studied by direct sequencing. Novel and known loss-of-function direct sequencing. Among the 144 alleles, 119 mutations were identified (83 %), including mutations were identified in 33 kindreds. We identified 14 new (IVS10+1G>A, F67fsX77, 63 truncating (stop or frameshift) mutations (53 %), 47 missense mutations (39,5 %), of R63fsX74, Q276fsX301, E713fsX407, R6X, Q108X, E123X, Y129X, R191X, R243X which 20 were possibly damaging and 27 possibly benign (www.bork.embl- Y450X, R770X, D679Y) and four recurrent mutations (IVS6-1G>A, N113fsX117, heidelberg.de/polyphen), 6 splice mutations (5 %), 2 in frame insertions/deletions, 1 P395fsX407, Q753X) of the ATP6V0A4 gene in 22 families. For the ATP6V1B1 gene, we abolition of the STOP codon. 72 different mutations were identified, 46 of them (64 %) identified two new (IVS2-1G>C, R394Q) and two previously described mutations unreported. No mutations were found in only 2 cases. Three mutations were recurrent: (I386fsX441, P346R) in 11 families. Surprisingly, seven probands with ATP6V0A4 gene T36M (14), c.9689delA (12) and c.5895dupA (9). Thus, screening of 6 exons (3, 14, 32, 36, mutations developed early SNHL, between the ages of two months and 10 years. No 57 and 58) allowed the identification of 43,8 % of mutations. We categorized mutations as mutation was detected in ten families. These data extend the spectrum of disease-causing severe (S) (truncating, possibly damaging missense, or splice mutation) or other than S, and mutations and provide evidence for genetic heterogeneity in SNHL. They also demonstrate genotypes as S/S (29) or non S/S (43). S/S genotypes were correlated with more severe that mutations in either gene may cause early deafness and highlight the importance of renal lesions than non S/S, for similar GA (p = 0,04). The correlation with hepatic fibrosis genetic screening for recessive forms of dRTA independent of hearing status. severity was NS. In conclusion, PKHD1 mutations were identified in 83 % of severe ARPKD cases, and truncating mutations in 53 %. Screening of only 6 exons identified 43,8 % of mutations. The severity of renal lesions was correlated with the presence of mutations that have drastic impact on protein synthesis. 1566 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 177 COD. PP 178 PTEC loaded with CDME is not a valid model to study pathogenesis of STEROID-SENSITIVE NEPHROTIC SYNDROME ASSOCIATED cystinosis WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY M Wilmer, L van den Heuvel, P Willems, A de Graaf-Hess, H-J Visch, H Blom, L DISEASE Monnens, E Levtchenko Department of Pediatric Nephrology Radboud University MK Gürgöze, HM Poyrazoðlu, Ý Dursun, Z Gündüz, R Düþünsel Department of Pediatric Nijmegen Medical Centre, The Netherlands Nephrology, Erciyes University Faculty of Medicine, Kayseri, TURKEY Radboud University Medical Centre , Dept Pediatric Nephrology, POB 9101, 6500 HB , Department of Pediatric Nephrology, Erciyes University Faculty of Medicine, Kayseri, Nijmegen , 6500 HB Nijmegen , The Netherlands The Netherlands TURKEY , 38119 Kayseri , Turkey

Studying the pathogenesis of cystinosis requires a model comprising the hallmark of this Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited disease: lysosomal cystine accumulation. The pathogenesis was previously studied in human kidney disease. Proteinuria can be determined frequently these patients. However, it proximal tubular epithelial cells (PTEC) loaded with cystine dimethylester (CDME), is not usually in the nephrotic range. We report a 4 –year-old boy with ADPKD that mimicking cystine accumulation. Using this model it was postulated that decreased ATP developed nephrotic syndrome. His proteinuria was 6gr/day and there were edema, production in cystinosis results in defective proximal tubular absorption, driven by Na,K- hypoalbuminemia and hyperlipidemia. Renal functions and serum complement level were ATPase. Recently, we found normal ATP generating capacity and only a slight decrease o f normal. There was also the ADPKD in his father and older brother. A standard prednisone ATP levels in cystinotic fibroblasts. Therefore, we compared mitochondrial ATP generation regime, beginning with 2 mg/kg/day, was started. After treatment, proteinuria disappeared. between cystinotic fibroblasts and control fibroblasts loaded with CDME. The kidney biopsy was not performed because of disappeared proteinuria. We present this Fibroblasts (n=2) were obtained from skin biopsies of controls and cystinotic patients. case due to that there are only few report of nephrotic syndrome associated with ADPKD. Medium was supplemented with 1mM CDME for 30min prior to experiments. Intracellular cystine levels were measured by HPLC and ATP levels were determined using ATP luminescence kit of Roche (nmol/mg protein). To monitor mitochondrial ATP production, cells were transfected with mitochondria targeted luciferase following perfusion with 5µM luciferin and CDME perfusion. Cystine levels increased in control fibroblasts from 0.1 to 3.4 and 10.4 after CDME loading compared to 1.8 and 5.1 in cystinotic cells. ATP levels were decreased by 7% in cystinotic fibroblasts and by 29% after CDME loading. Perfusion with 1mM CDME resulted in <10% mitochondrial ATP production after 15min. ATP generation remained intact in cystinotic fibroblasts. CDME loading results in dramatic decrease of mitochondrial energy generating capacity in contrast to normal ATP production in cystinotic fibroblasts. This questions the validity o f the CDME model for studying the pathogenesis of cystinosis.

COD. PP 179 COD. PP 180 Primary hyperoxaluria: Mutation Analysis in the AGXT Gene and Renal function in children with primary hyperoxaluria type 1 on Identification of an extensive intrafamilial Genotype-Phenotype conservative treatment Variability S Fargue, MF Gagnadoux, M Tsimaratos, F Janssen, B Llanas, B Boudailliez, G Champion, M T F Wolf 1,2, B B Beck 1, L Stapenhorst 1, J Devange 1, B Hoppe 1 1Department of MA Macher, B Ranchin, R Salomon, S Ta que, P Cochat. Pediatric Nephrology of the University Children’s Hospital and 2Department of Human Société de Néphrologie Pédiatrique & Department of Pediatrics, , Hopital Edouard-Herriot Genetics, Cologne University, Germany &Université Claude-Bernard , 69003 Lyon , France France University Children´s Hospital Cologne , Pediatric Nephrology, Kerpener Str. 62 , 50937 Cologne , Germany The renal function of 27 children with primary hyperoxaluria type 1 (PH1) was retrospectively studied once medical treatment had been started. The diagnosis was based Primary hyperoxaluria (PH) is a rare disease of the glyoxylate metabolism. End-stage-renal either on alanine:glyoxylate aminotransferase (AGT) enzymatic deficiency or on the disease is the consequence, if this disorder is left untreated. Approximately 90% of patients presence of a specific mutation in the patient or in siblings of an affected patient. The show urolithiasis or nephrocalcinosis as symptoms of PH in childhood. Additional conservative measures included high fluid intake i.e., 2 to 4 L/m2 per day, urine symptoms may be urinary tract infections or hematuria. Mutations in two genes are alcalinisation with potassium or sodium citrate/bicarbonate, and pyridoxine 10 to 20 mg/kg responsible for PH: (i) the AGXT gene for PH1 and (ii) the GRHPR gene for PH2. We have per day in responsive subjects. The mean follow-up was 7.0±1.3 [1.6–17.6] years. The performed mutation analysis for PH in a sequential way: (i) analysis of exons 1, 4 and 7 of mean age at first symptom was 37±7 months ; 6 children were diagnosed on familial the AGXT gene, (ii) if negative, analysis of the remaining 8 AGXT exons, (iii) if negative, screening. The mean age at start of treatment was 5.2±11.4 [0.9-12.3] years, and the mean analysis of the GRHPR gene by exon PCR and direct sequencing. In eight patients we age at the end of follow-up was 11.7±2.3 [2.7-21.0] years. Seventeen children were found 11 mutations in the AGXT gene, five of them are novel. One patient showed a pyridoxine responsive. Initial renal impairment was present in 11 patients and 6 already had published GRHPR gene mutation. chronic renal failure. The mean baseline GFR was 90±17 mL/min per 1.73m2 and the mean The most frequent found mutation was the c.508A>C mutation in exon 4 of the AGXT gene final GFR in patients without ESRD (N=23) was 108±21 mL/min per 1.73m2: 19 patients (4 of 11 mutations). The other mutations are scattered over the whole gene. had stable renal function, 8 experienced a decrease in GFR by more than 15 mL/min per In one kindred with a published mutation in exon 1 (c.33delC) we detected a remarkable 1.73m2 (4 of whom presented with initial renal failure), and 4 patients progressed to ESRD. intrafamilial genotype-phenotype variation: the index patient showed typical symptoms, but Fourteen patients suffered from stone passage during follow-up (mean number of episodes other carriers of the homozygous mutation were asymptomatic. This extensive clinical 2.2, up to 7) and 14 required either ESWL or open surgery. variability on the background of the same mutation indicates the existence of further In conclusion, an early aggressive conservative management may preserve renal function of modulating factors of the phenotype. compliant PH1 children. Pediatr Nephrol (2006) 21:1493–1635 1567

COD. PP 181 COD. PP 182 Renal function in adolescent and adult patients with phenylketonuria Identification of mutations ADAMTS 13 gene in children with atypical J. Gellermann ,J.B. Hennermann, S. Roloff, E. Mönch, U. Querfeld hemolytic-uremic syndrome (HUS). OHC, Center for Pediatric and Adolescent Medizine, Charité University Medical Center , Hye Won Park1, D Oh1, N Kim1, S Kim1, H I Cheong2, H S Ahn2, J S Kim3 Department Augustenburger Platz 1 , D-13353 Berlin , Germany Germany of Pediatrics, Pochon CHA University, Sungnam, Korea1 Department of Pediatrics, Seoul National University Children’s Hospital, Seoul, Korea 2, Department of Pediatrics, St. Mary Objective: Lifelong diet is recommended in patients with phenylketonuria (PKU). The Hospital, Cheongju, Korea3 effect of long-term diet on renal function has not been investigated yet. Dept of Pediatrics, Pochon CHA University , 351 Yatap-dong, Bundang-gu, , 463-712 Methods: We analyzed renal function in 67 adolescents and adults with PKU, aged 15 – 42 Sungnam , South Korea years, by measuring isotope clearance (51Cr-EDTA, 123J-Hippuran), creatinine clearance, blood retention parameters, urinary protein and electrolyte excretion, renal ultrasound und Hemolytic uremic syndrome Hemolytic uremic syndrome (HUS) and thrombotic twenty-four hour ambulatory blood pressure monitoring (ABPM). thrombocytopenic purpura (TTP) are considered to be different manifestation of one single Patients were divided into three groups according to: 1) current diet (CD) and daily protein syndrome of thrombotic microangiopathy (TMA) which is microangiopathic hemolytic intake: ICD < 0.8 g/kg, IICD 0.8 – 1.04 g/kg, IIICD > 1.04 g/kg; 2) life-long diet (LD) and anemia (MAHA), thrombocytopenia associated with formation of thrombi containing von cumulative years of life in which daily protein intake has exceeded dietary Willebrand factor (VWF) and subsequent organ dysfunction. recommendations (DGE 1985): ILD < 15 years, IILD 15 - 19 years, IIILD >.19 years. Von Willebrand factor (vWF) is a glycoprotein essential for platelet adhesion an d Results: With increasing protein intake, glomerular filtration rate (GFR) decreased aggregation. ADAMTS (a disintegrin and metalloportease, with thrombospondin 1-like significantly, measured by isotope clearance (ICD 111 ml/min, IICD 105 ml/min, IIICD 99 domains) 13 or its inhibitors. vWF-cp was identified as a member of ADAMTS family of ml/min. ILD 112 ml/min; IILD 103 ml/min; IIILD 99 ml/min) and by creatinine clearance metalloprotease, which cleaves vWF. Severe deficiencies of ADAMTS13 were reported in (ICD 118 ml/min, IICD 100 ml/min, IIICD 83 ml/min). Urinary calcium excretion TTP and atypical HUS patients. ADAMTS13 plays a pathogenic role in the development of increased in relation to protein intake (ICD 0.15 g/g creatinine, IICD 0.12 g/g creatinine, TTP. Mutations in the ADATMS13 gene have been causatively linked to recurrent, IIICD 0.21 g/g creatinine). Proteinuria was found in 17/63 patients and microalbuminuria in hereditary TTP/HUS. 5/62. 13/48 PKU patients showed arterial hypertension. A twelve-year-old boy presented with recurrent atypical hemolytic uremic syndrome with Conclusion: Dietary protein intake may account for impaired renal function in PKU neurologic manifestation of cerebral infarction and history of neonatal hyperbilriubnemia patients. The pathophysiology is not fully explained. We recommend routine renal function requiring exchange transfusion. The plasma ADAMTS13 activity of the boy was less than 3 tests in PKU patients on long-term dietary treatment. % of normal and those of his father, mother and brother were 56 %, 55 % and 62 %, respectively. ADAMTS13 inhibitors were not detected in all family members. Genetic analysis of this patient revealed as compound heterozygous state: one splicing mutation at 330+1G>A at the 5’ end of intron 3 in the metalloprotease domain and one novel missense muatation at I1217T on exon 26 in CUB domain of ADAMTS13.

COD. PP 183 COD. PP 184 LET US MAKE THE DIAGNOSIS IN THIS UNUSUAL CASE! Autosomal dominant policystic kidney disease (ADPKD) in children – M Koyun, A Gür Güven, S Akman, Y E Baysal, R Artan Akdeniz University, Medical one center experience. Faculty, Division of Pediatric Nephrology and Pediatric Gastroenterology, Antalya- D Runowski, T Jarmoliñski, M Pawelec Department of Nephrology and Dialysis, District TURKÝYE Children`s Hospital, Szczecin, Poland, e-mail: [email protected] , Akdeniz University, Medical Faculty, Division of Pediatric Nephrology , 07070 Antalya , Dept. of Nephrology and Dialysis, District Children`s Hospital , Úw. Wojciecha 7 , 70-410 Turkey Szczecin , Poland

A six-year old boy had been admitted with periorbital oedema at the age of 2.7 years. He ADPKD is diagnosed predominantly in adulthood between 3rd and 5th decade of life, but was the product of first degree consanginous marriage, whom had one stillbirth and two kidney abnormalities may be found in children before clinical symptoms of the disease. The spontaneous abortions. His weight , height , head circumference , blood pressure percentiles aim of study was to describe the clinical picture of the ADPKD diagnosed in childhood. were in the normal ranges. Physical examination revealed oedema below eyelids, The study group was composed of 13 children aged between 1-17 yrs. Initial symptoms, age pseudostrabismus, diffuse thin pigmentation on fundus and small nevus on iris edge, at diagnosis, present symptoms, family history and laboratory tests were analyzed. The premature graying of hairs, diffuse 0.5 mm hypopigmented skin lesions, narrow thorax, reasons of the first abdominal ultrasound were: family history of ADPKD in 9 children, hyperelasticity of the extremities. His psychomotor development was normal. pain in 3 and UTI in 1. Renal cysts were found between 1st and 13th yr of life: bilaterally in Hepatomegaly was detected on abdominal ultrasonography. 9 children, unilaterally in 3 and in one case in sole kidney. Time from the first symptoms to Initial laboratory data: urine pH: 6.0-6.5, urine glucose trace, urine protein (1+), diagnosis was 0-10 yrs. Vertical transmission of ADPKD was established in families. The microalbuminuria (+), urine sodium 57, potassium 19 mEq/l, BUN 19 mg/dl, serum disease was recognized in 2-6 persons of each family. Elevated blood pressure was found in creatinine 0.62 mg/dl, potassium 2.5 mEq/l, blood glucose 126; ALT 205 U/L, AST 104 4 children and renal insufficiency (RI) in 3. Urine analysis was normal in all children. U/L, GGT 190 U/L, ALP 811 U/L, triglyceride 207 mg/dl, phosphate 3.5 mg/dl, uric acid Myocardial hypertrophy was observed in 6 patients, among them in 3 without hypertension. 2.1 mg/dl. All necessary radiological, biochemical and serological tests for diagnosis Angio MR of the head was performed in 4 children with familiar history of stroke, but any including liver biopsy were performed and were within normal limits, except generalized abnormalities were found. aminoaciduria, tubular phosphate reabsorption of 86% and mosaic trisomi 22. During 3 Conclusions: 1/ The diagnosis of ADPKD is possible to be established in young age, but the years of follow-up his growth stunted, liver and spleen enlargement progressed, glomerular range of investigation children with family history is still debatable. 2/ The outcome of and tubular functions detoriorated; transaminases gradually increased. He has been on ADPKD in children is not clear, however the risk of RI and left ventricular hypertrophy peritoneal dialysis since February 2006. seems to be high. With his dysmorphic findings (premature hair graying, skin-eye lesions), progressive hypertransaminasemia and glomerular and tubular abnormalities: A new syndrome/ CDG- syndrome/ Paroxosomal disorder/ Mitochondrial disease (COX defect) could not be differentiated. 1568 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 185 COD. PP 186 Autosomal recessive polycystic kidney disease: growth and recombinant Renal hypoplasia without optic coloboma in a patient with PAX-2 gene human growth hormone therapy deletion C Fernández, M Navarro, L Espinosa, MC Meseguer, A Alonso, M Melgosa J Bravo E Benetti (1), L Artifoni (2), L Salviati (3), L Pinello (4), S Perrotta (5), G Montini (1), G Hospital Universitario La Paz , Paseo de la Castellana 261 , 28041 Madrid , Madrid Spain Zacchello (1), L Murer (1). (1)Nephrology, Dialysis and Transplant Unit, Department of Pediatrics, Univ. of Padua (2)Laboratory of Pediatric Nephrology, Department of Pediatrics, Children with autosomal recessive polycystic kidney disease (ARPKD) may have growth Univ.of Padua (3)Clinical Genetics and Epidemiology Service, Dept. of Pediatrics, Univ.of retardation, which is not fully understood. Padua (4)Ophthalmology Unit, Department of Pediatrics, University of Padua (5) Aim of study: retrospective study of ARPKD children diagnosed between 1967 and 2003. Department of Pediatrics, Second University of Naples Growth, final height and response to therapy with recombinant growth hormone (rhGH) are Department of Pediatrics - University of Padua , Via Giustiniani 3 , 35128 Padua , Italy analyzed. Material: 40 ARPKD children (22 boys, 18 girls), mean follow-up 7.88 6.23 years. PAX-2 is a transcriptional regulator of the paired-box family and is widely expressed during Results: 31 children (mean age 10.8 4.5 years) are normal height (Z- score -2SDS) the development of both ductal and mesenchymal components of the urogenital system. while 9 (mean age 13 3.2 years) are short (Z-score -2SDS). There is no significant Heterozygous mutations in the human PAX-2 gene have been previously reported in difference (p0.05) in glomerular filtration rate (GFR) between either group: 6947 patients with autosomal dominant renal-coloboma syndrome and more recently in patients ml/min/1.73m2 vs 5844 ml/min/1.73m2, nor in the incidence of hepatic complications, with isolated renal hypoplasia and isolated vescico-ureteral reflux (VUR). 45% vs 44% We describe a 6-year-old female with a 7.9 Mb interstitial deletion of the long arm o f Data for final height are available for 13 children: males (age 16.5 years, N= 7): 165 chromosome 10, involving PAX-2 locus as a whole. 8.9 cm (152-173cm);Z- score (-3.1-0 SDS). Females (age 15.5 years, N= 6): 159 7.6 She first presented at the age of 5 mo. with mild chronic renal failure, associated to facial cm (149-169cm); score -Z (-2.18-1.1 SDS) GFR was not significantly different: 5026 dysmorphic features, retarded psychomotor development and joint laxity. Renal ml/min/1.73m2 in the males group vs 6044 ml/min/1.73m2 in the females group. ultrasonography revealed a left hypoplastic kidney and a contralateral dysplastic one. No 13 children (8 boys, 5 girls) aged 8.5 4.1 years received rhGH therapy. Duration of VUR was observed on contrast voiding cystography. Cerebral MRI showed a mild therapy was 35 26 months. Initial GFR was 4529 ml/min/1.73m2 and final GFR was 35 dysmorphism of the left lateral ventricle. Ophthalmological examination excluded the 28 ml/min/1.73m2 (p0.05). Significant increase in height Z-score was noted after rhGH presence of optic nerve coloboma. No anomalies to other organs were found in further treatment: Z-score before 1.88 0.79 vs -1.17 0.75 after therapy ( p=0.028). investigations. Conclusion: Growth retardation in ARPKD children is not exclusively related to chronic To our knowledge, this is the first reported case of human PAX-2 gene deletion. The renal insufficiency. Treatment with rhGH improves growth. observed phenotype of renal hypoplasia confirms that PAX-2 haploinsufficiency is strongly associated to anomalies of kidney development, but the absence of optic coloboma raises an issue about its role in determining anomalies of optic nerve. Moreover, our observation suggests the matter of screening PAX-2 gene for deletion both in syndromic and isolated anomalies of kidney development.

COD. PP 187 COD. PP 188 Autosomal recessive polycystic kidney disease: clinical presentation and A novel umod gene mutation associated to glomerular and tubular cysts long-term outcome G Caridi (1), E Benetti(2), M Dagnino(1), L Rampoldi(3), A Zucchini(4), G Zacchello(2), M Navarro C Fernández, L Espinosa, A Peña, AAlonso, M Meseguer, M Melgosa GM Ghiggeri(1), L Murer(2). (1)Nephrology Unit, G. Gaslini Children`s Hospital, Genoa, Hospital Universitario La Paz , Paseo de la Castellana 261 , 28041 Madrid , Madrid Spain (2)Nephrology, Dialysis and Transplant Unit, Department of Pediatrics, Univ. of Padua (3) DIBIT-San Raffaele Scientific Institute, Milan (4)Pediatric Unit, Hospital of Faenza On Autosomal recessive polycystic kidney disease (ARPKD) is an important cause of renal and behalf of MCDK Italian Consortium hepatic- related morbility and mortality in childhood. Department of Pediatrics - University of Padua , Via Giustiniani 3 , 35128 Padua , Italy Aim of study: We describe the clinical presentation, course and renal evolution of ARPKD children diagnosed between 1967 and 2003 in our pediatric nephrology department. Mutations of the UMOD gene, encoding uromodulin, have been associated to medullary Material: Retrospective study of 49 ARPKD children (26 , 23♀ ) mean follow-up 8.46 ± cystic kidney disease (MCKD) and familial juvenile hyperuricemic nephropathy (FJHN). In ♂ a previous report, we also described a UMOD mutation in a family with glomerulocystic 6.24 years. kidney disease (GCKD). Results: The median age at diagnosis was 15 months (54.3% were diagnosed in their first We herein report on an 11-year-old boy presenting with chronic renal failure, a family month of life). Neonatal pulmonary pathology was documented in 12,2%. Evidence of history (father) of an undefined renal-transplantation-requiring nephropathy and a personal portal hypertension was found in 32.6%. Urinary tract infections occurred in 22.4% (only 1 history of hyperuricemia and urine concentrating ability impairment preceding the onset of VUR). 69.3% developed arterial hypertension; of these, 65.2% required treatment (1-5 renal failure. Renal ultrasonography demonstrated slightly reduced bilateral kidney volumes drugs). Mean age at start of blood pressure medication, 1 year. Patient survival rate was and cortical hyper-echogenicity, with two tiny cysts in the left kidney. Renal biopsy showed 93.8% at 1 year and 89.7% at 15 years. Actuarial renal survival rate was 100% at 5 year, up to 50% of glomeruli featuring an enlargement of Bowman’s space (glomerular cysts), 92% at 10 years and 88% at 15 years. 6 children (mean follow-up 7.9 6.2 years) with tubular atrophy and dilatation, mild inflammatory infiltrate and interstitial fibrosis as developed ESRD; 17 (mean follow-up 11.56.6 years) had chronic renal insufficiency well. Unlike previously reported cases, no uromodulin positive globular aggregates within (CRI) and 22 (mean follow-up 6.3 4.4years) has normal glomerular filtration rate (GFR). the cytoplasm of tubular cells were observed by immunostaining. Hypertension and hepatic complications were significantly higher (p0.05) in children with Genetic analysis revealed a novel heterozygous mutation of UMOD gene c.149 renal insufficiency (ESRD and CRI) G>C;p.Cys50Ser, which involves the first EGF domain of UMOD gene. The mutation Conclusions: Patient survival is 90% at 15 years, with slow rate of end-stage renal segregated in both the proband and his father. progression. Children with chronic renal insufficiency showed a significantly higher rate of This novel UMOD mutation, associated to the evidence of both glomerular and tubular hepatic complications and of systemic hypertension than children with a normal GFR cysts, confirms the phenotypic heterogeneity of UMOD mutation associated diseases. Pediatr Nephrol (2006) 21:1493–1635 1569

COD. PP 189 COD. PP 190 NPHP2 mutations in infantile nephronophthisis. Phenotype-Genotype correlation in Neonatal Bartter syndrome 1R Salomon, 1V Moriniere, 1O Gribouval, 1F Legendre, 2P Cochat, 3C Guyot, 4D Morin, K Brochard1, O Boyer2, N Le Pottier3, X Jeunemaître3, R Vargas-Poussou3,4 and the 5H Nivet, 6M Foulard, 1M Delous, 1S Saunier, 1C Antignac. 1 Inserm U 574, Hôpital Consortium for study of primary tubulopathies. 1Service de Néphrologie Pédiatrique Necker Enfants Malades, Université René Descartes, Paris, France. 2 Department of Hôpital Robert Debré, Paris 2Service de Néphrologie Pédiatrique. Hôpital Necker, Paris. Pediatrics, Hopital Edouard Herriot, Lyon, France. 3 Pediatric Nephrology , Hopital Mere et 3Département de Génétique Hôpital Européen Georges Pompidou, Paris 4Département de Enfant, Nantes, France. 4 Department of Pediatrics, Hopital Arnaud-de-Villeneuve, Pédiatrie Médicale CHU de Rouen. Montpellier, France. 5 Pediatric Nephrology, Hopital Gatien de Clocheville, Tours, France. 1Service de Néphrologie Pédiatrique Hôpital Robert Debré , 48, boulevard Sérurier , 75935 6 Department of Pediatrics, Hopital Jeanne-de-Flandre, Lille, France. Presenting author: R Paris , France Salomon Université René Descartes , Hôpital Necker 149, rue de Sèvres , 75015 Paris , France Neonatal Bartter syndrome, an hereditary hypokalemic salt-losing tubulopathy, is caused by mutations in the genes encoding either Na+-K+-2Cl- cotransporter (NKCC2), K+ channel Nephronophthisis (NPH) is an autosomal recessive chronic tubulointerstitial nephropathy (KCNJ1), Cl- channel (CLCNKB), or barttin subunit (BSND). which leads to end-stage renal disease (ESRD) generally during adolescence in the most We retrospectively analysed the clinical and biochemical data and evolution of 25 common juvenile form. An infantile form has been described which is characterized by genetically defined children, 11 boys and 14 girls with mutations in BSND (n=2), KCNJ1 enlarged kidneys with cysts widely distributed throughout the cortex and medulla. The (n=15), NKCC2 (n=5) and CLCNKB (n=3) genes. The mean follow-up was 7 years (range INVS/NPHP2 gene which encodes for inversin is responsible for the infantile form. We 0,8–18 years). have analyzed INVS/NPHP2 in a cohort of 42 unrelated patients with NPH who reached 96% of patients with a CLCNKB mutation and 100 % of patients with other gene mutations ESRD before the age of 6 years (mean age 33 months). presented with polyhydramnios and premature birth. Mean birth term was 31, 32, 34 and 36 We found INVS/NPHP2 mutations in 16 patients from 14 (33.3%) unrelated families. Four weeks for BSND, KCNJ1, NKCC2 and CLCNKB mutations patients, respectively. In all of them were previously published1. ESRD occurred at a mean age of 17 months (5-36). cases, polyuria, failure to thrive and episodes of dehydratation were noted in the neonatal Situs inversus was present in two patients one of whom had also hepatic fibrosis and period. Hypokalemia was constant, except in children with KCNJ1 mutations (78.5% of pulmonary stenosis. Hepatic fibrosis was present in another patient and cone-shaped them had transient hyperkalemia). Metabolic alkalosis, renal salt wasting, hypercalciuria epiphyses were present in two sisters in another family. Retina was normal in all cases. and nephrocalcinosis were present in 62,5%, 100%, 87,5% and 12,5% of cases. Clinical Arterial hypertension was present in 4 patients. Renal histological analysis when available stabilization and catch-up growth were observed in 21 children under indomethacin with a was characteristic, with cystic dilations of the cortical tubules and Bowman’s spaces in moderate reduction of hypercalciuria but 90% developed nephrocalcinosis at a median age most cases. of 6 months. One child with BSND mutation developed chronic renal insufficiency at birth, We studied two additional patients with NPH and situs inversus who reached ESRD later; and another one with CLCNKB mutation at 6 months. none harboured INVS/NPHP2 mutations. Neonatal Bartter’s syndrome was mostly linked to KCNJ1 mutations (60%). Most clinical In conclusion, INVS/NPHP2 mutations are found in approximately one third of infantile features are well controlled under treatment but hypercalciuria may persist and chronic renal NPH. disease may develop occasionally even in absence of nephrocalcinosis. 1: Otto et al. Nat Genet 2003; 34:413-20.

COD. PP 191 COD. PP 192 Genotype-phenotype correlation in 60 cases of autosomal recessive Does the diagnosis of multicystic dysplastic kidney require a screening polycystic kidney disease (ARPKD) of family ? – a case report S Fargue(1), L Michel-Calemard(1-2), A Liutkus (1), F Nobili(3), M-P Lavocat(4), R M Zaniew, J Zachwieja, D Sobczyk, A Siwiñska Bouvier(1), M-P Cordier(1), Y Morel(2), P Cochat(1) (1) Reference Centre for Hereditary , Department of Pediatric Nephrology, Szpitalna 27/33 street , 60-572 Poznañ , Poland Renal Diseases, Hôpital Edouard Herriot, France (2) Laboratoire de Biologie Moléculaire et Endocrinienne, Hôpital Debrousse, Lyon, France (3) Pediatric renal Unit, Besançon, France Among congenital urinary tract anomalies, there are malformations of renal tissue (4) Department of Pediatrics, Saint-Etienne, France development (renal agenesis, dysplasia, and hypoplasia), which usually occur sporadically Reference centre for hereditary Renal Diseases , Hôpital Edouard Herriot , 69437 Lyon , or as a part of congenital syndromes. However, there has been described few families with France varying degrees of agenesis and/or dysplasia of one or both kidneys in the same family. This anomaly was designated as hereditary renal adysplasia (HRA). An autosomal dominant PKHD1, gene responsible for ARPKD, has recently been characterized. In 2003, we had set trait of inheritance with incomplete penetrance and variable expression was reported in up mutation analysis by direct sequencing of the 67 exons in order to propose reliable direct HRA so far. One of the genes responsible for this anomaly is located on chromosome 6p. genetic diagnosis. A total of 76 mutations (54 different) were identified: 8 nonsense, 34 We report a family with HRA in which three members within two generations were missense, 7 frameshift and 5 splice site mutations. affected. The proband was a 4,5-year-old girl who was admitted to our department for 60 cases from 45 families were investigated between 2003 and 2006. Comparisons were evaluation due to urinary tract infection and finally diagnosed as having a right multicystic based on Fisher test.. We analysed the distribution and clinical impact of truncating dysplastic kidney (MCDK). Family history revealed the mother has a left renal agenesis. mutations (TM) leading to 3 groups: G1 (no TM): N=36, G2 (1 TM): N=18 and G3 (2 TM): She delivered a female preterm neonate who antenatally was found to have a left renal N=6. 34 samples came from prenatal diagnosis. Pregnancy termination was performed in 13 agenesis and a right MCDK. Ultrasonographic examination of this child at 24 weeks of cases: G1=6, G2=3, G3=4 (P=0.04). Neonatal death occurred in 9 cases: G1=2, G2=5, gestation showed accompanying anhydramnios. This child died shortly after a labour, G3=2 (P=0.004). 2 children died at 4.25 (G1) and 0.5 years of age (G2). 36 patients are still presumably as a result of pulmonary insufficiency. Conclusions: This case report provides alive: G1=27, G2=9, G3=0 (P=0.001) at a median follow-up of 7.4 (G1) and 5.3 years (G2). the support of an autosomal dominant pattern of inheritance in HRA and the variable Arterial hypertension was present in 50% of surviving patients, starting during neonatal expression of this anomaly in family. In case of renal dysgenesis (agenesis, dysplasia, period for 22% and at median age of 0.8 year for others. GFR (mL/min per 1.73m²) was > hypoplasia), a careful screening of the proband`s family is encouraged. 80 in 20 patients (G1=16, G2=4) at a median follow-up of 5.4 years, 80 to 40 in 8 patients (G1=4, G2=4) at 4.2 years, < 40 in 7 patients (G1=6, G2=1) with ESRD for 3 of them. 9 patients had portal hypertension (G1=7, G2=2) complicated by gastrointestinal bleeding in 7 (G1=5, G2=2). These results show that heterogeneous phenotype of ARPKD may correlate with genotype. 1570 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 193 COD. PP 194 Clinical and genetic features in paediatric patients with Bartter and Early onset end-stage renal failure in Oculo-cerebro-renal syndrome Gitelman syndrome: observational study phenotype: Novel occurrence. R Bellantuono, M Giordano,T DePalo, R Calabrese*, R Penza*, D A Caringella Pediatric AJ Al Mosawi Nephrology and dialysis Unit, Pediatric Hospital "Giovanni XXIII" * Pediatric Clinic, University Hospital in Al kadhimiyia , Head of the department of pediatrics , 70025 University of Bari, Bari Baghdad , Iraq Ospedale Pediatrico "Giovanni XXIII" , via Amendola 207 , 70126 Bari , Italy Background: The Oculo-cerebro-renal syndrome (OCRS) is a rare disorder characterized by Aim of the study was to find out clinical, biochemical and molecular signs for an early congenital ocular and cerebral defects, and renal tubular dysfunction with later renal onset distinction between Gitelman syndrome (GS) and Bartter syndrome (BS) and to critucally of renal failure during the fourth. The paper reports the novel occurrence of early end-stage evaluate treatment and patient’s outcome. renal failure (ESRF) in OCRS phenotype. Twenty children (14 males and 6 females) with a mean age at the diagnosis of 2.97 years Patients and Methods: From 1994 to 2005 four patients (two boys and two girls) with (0.08 – 8 years) were included into the study. 13 were affected by BS, 7 by GS; mean OCRS phenotype were observed. All of them have congenital cataract(s), hypotonia and follow-up was 9.3 years (1.2 – 20 years). All BS patients were treated with indomethacin hyporeflexia and renal dysfunction. (1.86 ± 0.5 mg/kg/die), ranitidine and KCl. GS patients were receiving supplementing Results: The ocular abnormalities in three patients were similar to those reported in the therapy with Mg and K. classical OCRS of Lowe consisting of cataract(s) and glaucoma. One patient (boy) has Typical BS clinical signs were found: early presentation (0.77 ± 0.7 vs. 5.71 ± 2.06 years); immature cataracts, and bilateral congenital chorioretinal hypoplasia. The 2 boys have premature delivery and polihydramnios, polyuria and polydipsia and poor growth. GS was nystagmus during infancy, in one of them nystagmus was not present at the time of referral. typically characterized by neuromuscular signs (spasm, hypotonic muscles and seizures). All the patients have hypotonia and hyporeflexia characteristic of Lowe OCRS.In one Main biochemical differences were low serum potassium levels (p<0.005) and low urine patient (girl) hypotonia and hyporeflexia occurred late and was not present during the first 3 osmolarity (p<0.005) in BS when compared to GS. Plasmatic levels of renin, aldosterone years of life. Three patients have global developmental delay. One patient has normal IQ and magnesium were significantly decreased in BS than GS patients, as well calciuria and and her language was well developed. All the patients reached ESRF during the first 6 years fractional excretion of chloride (FeCl) (p<0.01). of life and required dialysis. All of them have microscopic hematuria, albuminuria, and 11 patients with clinical BS presented mutations of ClCNKB gene (BS type III). One of casturia suggesting glomerular disorder. None of them have evidence of renal tubular these patients presented a double mutation of ClCNKA e ClCNKB genes. Two children dysfunction. Three patients died from uremia during the first decade of life. It was not with neonatal phenotype showed the first, a deletion of KCNJ1 (BS type II) gene, the possible to follow the fourth patient. second, a deletion of SLC12A1 (BS type I) gene. Six of the 7 GS patients presented Conclusion: This is the first paper reporting early onset of ESRF during the first decade of deletions in SLC12A3 gene. life In all BS children, the proposed treatment gained a polyuria reduction, increase of growth speed and K serum levels, a good alkalosis control. No severe adverse events were reported. In GS a neuromuscular symptoms regression was also observed. Only 2 BS patients evolved toward a chronic renal failure.

COD. PP 195 COD. PP 196 COQ2 gene mutations cause primary Coenzyme Q10 deficiency and NAIL PATELLA SYNDROME: REPORT OF A TURK ISH FAMILY early childhood nephropathy WITH N246K MUTATION IN THE LMX1B GENE F Diomedi-Camassei1, S Di Giandomenico1, G Caridi3, F M Santorelli1, F Piemonte1, G N Cengiz*, E Baskin*, M Derbent*, BT Yilmaz*, YE Bikmaz*, G Gonlusen**, Y Uslu*, A Montini4, G M Ghiggeri3, L Murer4, L Barisoni6, A Pastore1, A Onetti Muda5, E Bertini1 Anarat**, I McIntoch*** Depts of Pediatric Nephrology, Pathology, Genetics, Baskent and F Emma2. 1Department of Laboratory Medicine (Divisions of Pathology, Molecular University*, Cukurova University**, John Hopkins University***, Adana, Ankara, Medicine, and Biochemistry) and 2Department of Nephrology and Urology (Division of Baltimore, TURKEY and USA Nephrology and Dialysis), Bambino Gesù Children’s Hospital and Research Institute, Baskent University hospital , Dept of Ped Nephrology 6.cadde 72/3 , 06490 Ankara , Rome, Italy. 3 Division of Nephrology, G. Gaslini Institute, Genoa, Italy 4 Department of Turkey Pediatrics, Division of Nephrology, University of Padua, Italy 5 Department of Pathology , La Sapienza University, Rome, Italy 6 Department of Pathology, New York University, Nail-patella syndrome (NPS) is an autosomal dominant disorder with a high penetrance, but New York, NY, USA varieable expressivity and wide pleomorphism It is characterized by dysplastic nails, absent Bambino Gesù Children`s Hospital and Research Institute , Division of Nephrology and or hypoplastic patellae, elbow dysplasia, iliac hornes, open-angle glaucoma and progressive Dialysis, P.zza S. Onofrio, 4 , 00165 Rome , Italy nephropathy. Nephropathy has been found in 30%-40% of affected individuals and may cause end stage renal failure. We report on a family in which several members were Recently, mutations in the COQ2 gene, which encodes for the para-hydroxybenzoate- affected by NPS associated with severe renal involvement. Index case is a 14-year-old girl. polyprenyl-transferase enzyme of the CoQ10 synthesis pathway, have been identified in one She is the second child of unrelated parents. Her father, whose own father, uncle, three family with steroid resistant nephrotic syndrome. sisters had died from end stage renal failure and NPS. She had dysplastic nails with Herein, we report two novel families with COQ2 mutations. Patient #1 was found to be a triangular lunulae, bilateral antecubital pytergia, joint contractures on ankles and wrists. In compound heterozygous for a c.590G>A(p.Arg197His) and a c.683A>G(p.Asn228Ser) the radiologic evaluation, bilateral iliac horns were detected, elbows were dysplastic and mutation. He presented with steroid resistant nephrotic syndrome at the age of 18 months, patella was normal. She had nephrotic range proteinuria, high creatinine levels. Renal secondary to a collapsing glomerulopathy. He had no extra-renal symptoms. Patient #2 biopsy was consistent with NPS. Molecular analysis revealed N246K mutation in the carried a homozygous c.437G>A(p.Ser146Asn) mutation in the COQ2 gene. He presented homeodomain of LMX1B gene in the family members. Characteristic clinical features and at five days of life with a rapidly progressive glomerulonephritis, leading to end-stage renal genotype-phenotype correlations are discussed within the context of molecular analysis. failure. Subsequently he developed a progressive epileptic encephalopathy and died at the age of 6 months. Ultrastructural examination of these biopsies, including the two previously reported patients, showed in all cases dysmorphic mitochondria in the glomerular cells. Biochemistry analysis showed decreased activities of complex II+III in muscle and renal specimens of both patients. CoQ10 concentrations were markedly reduced in the renal tissue of patient #1 (4 mmol/g fresh tissue, controls 27±3) , but not in muscle extracts (12.4, normal 18.3±6 mmol/g fresh tissue), and were found to be severely reduced in both renal (4 mmol/g fresh tissue) and muscle (0.8 mmol/g fresh tissue) specimens of patient #2. We conclude that renal disease in patients with COQ2 mutations can be very heterogeneous and that the nephropathy is not always associated with neurological signs. This diagnosis should be suspected when electron microscopy shows dimorphic mitochondria in glomerular cells. Pediatr Nephrol (2006) 21:1493–1635 1571

COD. PP 197 COD. PP 198 MYCOPHENOLIC ACID REACHES THERAPEUTIC LEVELS Favorable glycated hemoglobin and cardiovascular profile in kidney- WHERE MYCOPHENOLATE MOPHETIL DOES NOT transplanted children in treatment with basiliximab, tacrolimus, R Vilalta (1), A Vila (1), J Nieto (1), E Lara (1), A Madrid (1) and M Quintana (1). (1) mycophenolic acid and tappered steroids. Pediatric Nephrology Department, Vall dHebron Hospital, Barcelona, Spain. R Vilalta (1), A Vila (1), J Nieto (1), E Lara (1), A Madrid (1) and M Quintana (1). (1) Vall d`Hebron Hospital , Pediatric Nephrology Department, Vall dHebron Hospital. Passeig Pediatric Nephrology Department, Hospital Vall dHebron, Barcelona, Spain. Vall dHebron n 119-129 , 08035 Barcelona , Spain Spain Pediatric Nephrology, Hospital Vall dHebron , Passeig Vall dHebron n 119-129 , 08035 Barcelona , Spain Spain Body: Background: In kidney transplanted children , is difficult to obtain blood levels of mycophenolic acid between 2 and 4 microg/ml, instead use of mycophenolate until 30 Background: Some concern has been raised related to the use of tacrolimus in pediatric mg/kg/day and / or t.i.d. Using directly mycophenolic acid, instead off the salt transplantation because its toxicity against pancreatic beta-cells. mycophenolate mophetil, could help to reach target levels. Objective: To describe our experience in 31 kidney- transplanted with an immunosuppressor regime based on tacrolimus.

Aim: To describe pharmacocinetics of micophenolic acid in eight kidney-transplanted Patients and methods: 18 boys and 13 girls (mean age 9 +/- 8 years) were transplanted in a children, over a period of 1.2 +/-0.8 years. two year period from a cadaveric donor ( mean age 11+/- 9 years). Basiliximab was employed at days 0 and 4 post-trasplant period, and tacrolimus was administered by mouth in the first 24 hours post-trasplant (0.15 mg/kg/day) to reach levels between 6 and 10 mcg/ml. MMF was administered at the same and steroids were administered and withdrawn Patients and methods: Eight patients (5 boys,3girls) aged 7+/-1.8 years, received a completely at the 360th day in 92 % of patients. Lipid profile and adverse events were cadaveric-kidney transplant. Induction was made with basiliximab, and after was started monitored. cyclosporine or tacrolimus (4-4), tapered steroids (withdrawed at 12 months in 6 cases and maintained at 0.15 mg/kg/day in 2), and mycophenolate mophetil (25-30 mg/kg/day) b.i.d. Results: Tacrolimus levels were maintained at 8 +/- 2.2 micg/ml at the 3 first months and or t.i.d. During 1 +/- 0.3 years. mycophenolic acid levels reached were between 0.8+/-0.3 after through the follow-up period, between 6 +/- 2.3 microg/ml. Mean hemoglobin A1c microgr/ml. When mycophenolic acid tablets were available , all of them were switched to levels did not differ between baseline (5.54%) at 12 and 48 months (5.48+/- 0.24%). New- mycophenolic acid. onset post-transplant diabetes mellitus did not occur at all. Mean total cholesterol and triglycerides were significantly lower than the baseline at 12 and 24 months post- transplantation (211 +/- 47.5 vs. 192.8 +/- 43.6 mg/dL, p = 0.005 and 156.2 +/- 33.2 vs. Results: After the replacement was made , blood levels obtained (8 +/-3 days), were 1.5 to-5 124. +/- 26. mg/dL, p < 0.001, respectively). Creatinine levels were maintained between 0.4 microg/ml (median 3.2), far more closer to the target 2-4 microg/ml. No gastrointestinal and 1.2 mg/dl. disturbances were registered. Follow-up time : 72 +/-18 days. Conclusions: Our data suggest that cautious use of tacrolimus provide a safe and useful therapeutic approach to pediatric kidney-transplant. Conclusion: Mycophenolic acid reaches therapeutic levels were mycophenolate does not. If mycophenolic acid would be available in syrup, could be used in patients under 5 years. It is necessary to follow these patients to rule out enzymatic induction and drop again to low levels

COD. PP 199 COD. PP 200 Ebstein-Barr PCR in kidney-transplanted children could be another Induction of regulatory T cells following prophylactic treatment with parameter to individualize immunosuppression. photopheresis in renal transplant recipients. R Vilalta (1), A Vila (1), J Nieto (1), E Lara (1), A Madrid (1), M Quintana (1), T Tortola L Dello Strologo(1), A Lamioni (2), R Carsetti (2), A Legato (1), A Landolfo (3), G Isacchi (2) and G Codina (2). (1)Pediatric Nephrology Department, Hospital Vall dHebron, (3,5), L Massella (1), Francesco Emma (1), Gian Franco Bottazzo (4) (1) Nephrology and Barcelona, Spain and (2) Microbiology Department, Hospital Vall dHebron, Barcelona, Urology Department, Research Center (2), Department of Oncohaematology and Barcelona, Spain. Transfusion Medicine (3), Scientific Directorate (4) Bambino Gesú Children`s Hospital, Pediatric Nephrology, Hospital Vall dHebron , Passeig Vall dHebron n 119-129 , 08035 Scientific Institute and Department of Biopathology and Immunohaematology Section, Barcelona , Spain Spain University "Tor Vergata" (5), Rome, Italy. Bambino Gesù Children`s Hospital , Nephrology and Urology Dept. Piazza S. Onofrio 4 , OBJECTIVE: To determine the role of Ebstein-Barr PCR in early diagnosis of infection in 00165 Roma , Italy kidney-transplanted children. Extracorporeal photopheresis (ECP), originally used to treat cutaneous T cell lymphoma, BACKGROUND: Ebstein-Barr virus (EBV) is related to post-transplant has also been applied to the therapy of transplant rejection. lymphoproliferative disorders (PTLD) and also with other clinical situations in wich there is Our aim was to investigate the biologic response in 4 children with kidney transplantation polyclonal expansion of B-lymphocytes. Drastic reduction or withdrawal of receiving photopheresis as a prophylactic treatment initiated immediately after transplant. immunosuppression with anti-viral therapy with valganciclovir for EBV is the primary All of them received conventional immunosuppressive therapy and two of them received treatment of both entities. ECP in association: 6 applications over three weeks. After a six-month follow up, the clinical course was favorable in all patients; no signs of rejection were detectable in the CASE REPORT: A young boy 6 years-old, IgG EBV positive, received a cadaveric kidney biopsy taken at the 6th months. transplant (EBV negative) at 5 years of age because an hemolitic-uremic syndrome. He was Compared to control transplanted patients, in both ECP treated patients, the frequency of treated with basiliximab, FK, mophetil mycophenolate (MMF) and tappered steroids. FK Treg cells increased at day 14, after 4 ECP cycles, with TNF-a starting to decrease at the levels were maintained between 8 and 10 ng/ml and MMF between 1 and 1.5 mcg/ml. same time. One year later, both TNF-a and IFN-g serum levels were similar between the two groups. In contrast, at one year, we found in ECP treated patients a persistent increase EVOLUTION: At the 8th month post-transplant, he developed a febrile necrotic tonsillitis of Treg cells, which were negative for CD69 activation markers, but expressed Foxp3. After with a PCR title of 77000 copies, and an histologic study showed polyclonal expansion of anti-CD3 stimulation, the same cells did not proliferate, expressed high levels of membrane B-lymphocytes. Immunosuppression was reduced to obtain FK levels of 2-2.5 ng/ml and CTLA-4 and suppressed the CD4+CD25- proliferation, all parameters consistent with the MMF of 0.8-1.2 mcg/ml. Oral valgancilovir was started (600 mg/m2/day). 4 weeks later, actual definition of Treg cells. EBV PCR title was 47000, with no closure of tonsille lesions. 8 weeks later, EBV PCR In conclusion: circulating Treg cells increase after ECP and, most relevantly, their increase under 5000 copies was achieved with resolution of tonsille lesions. Valganciclovir was still persists after one year without the need of a recall ECP. mantained 3 months. In a 6 months follow-up EBV PCR title was mantained under 5000 Kidney biopsies will demonstrate in the long term follow up, whether the persistent increase copies with an optimal renal function (creatinine 0.4 mg/100 ml). of Treg cells induced by ECP has a beneficial effect in preventing chronic rejections.

CONCLUSION: EBV PCR monitoring of kidney-transplanted children could anticipate or at less help control of non-PTLD EBV disorders, and always indicates treatment if EBV PCR is over 5000 copies. 1572 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 201 COD. PP 202 Gross proteinuria post transplant in a child with nephrotic syndrome of Febrile Urinary Tract Infections following Renal Transplantation in the Finnish type – mechanical versus immunological pathogenesis Childr en: A Retrospective Review at Three German Transplant F Lorton, B Letavernier, A Isapof, G Deschênes, A Bensman, T Ulinski Centers Hôpital Trousseau , Department of Pediatric Nephrology , 75012 Paris , France U John*, A Schulze Everding, E Kuwertz-Bröking, M Bulla, DE Müller-Wiefel, J Misselwitz, MJ Kemper Nephrotic syndrome of the Finnish type (NSF) is caused by mutations in the NPHS1 gene Universitiy Children`s Hospital , Kochstrasse 2 , 07745 JENA , Germany which codes for nephrin. Renal transplantation (Tx) after bilateral nephrectomy is a successful longterm treatment option. Nephrotic proteinuria may reoccur after Tx as a result Background: Adult data suggest that urinary tract infections occur frequently after renal of alloimmunisation against normal nephrin. transplantation and contribute to mortality and graft loss; data in children are limited. We We report a 17-month-old female with NSF transplanted with her father’s kidney. On day 6 evaluated prevalence, short and long-term morbidity and confounding factors of febrile UTI post Tx, gross proteinuria (10 g/L) was detected in the morning collection and almost (fUTI) after renal transplantation. disappeared after day time (0.2 g/L), concomitant with a moderate elevation of serum Methods: In a retrospective cross-sectional study of three centres, we analyzed data on 110 creatinine. Microscopic hematuria (10-50 red blood cells/l) was present and remained children (n=66 male). Mean chronological age is 15.1+/-4.5 years. Age at transplantation stable over the first 2 weeks post Tx. Similar changes between gross proteinuria after night was 10.2+/-4.6 years. time and almost normal proteinuria after day time persisted for 10 days. Night time Results: In 40/110 (36%) patients at least one fUTI occurred after a median time of 0.98 proteinuria decreased progressively and reached normal values after 2 weeks. The renal years (range 0.02–8.96) with recurrences in 11 (28%). During the fUTI, serum creatinine biopsy and renal Doppler examination were normal and no anti-nephrin antibodies were rose from 1.15+/-1.13 mg/dl to 1.83+/-1.69 mg/dl, (p<0.001), declining to baseline values detected in the patient’s serum. after treatment. At last follow-up, however, calculated mean GFR was comparable between We hypothesize that a moderate compression of the renal vein altered renal hemodynamics fUTI and non-fUTI groups (75+/-26 vs. 71+/-22 ml/min/1.73m2). FUTI were significantly and resulted in proteinuria. The nocturnal proteinuria was explained by her ventral sleeping more frequent in girls compared to boys (22/44 vs. 18/66, p<0.05), in whom they occurred position, on the graft side, after the first days in intensive care unit, where a supine sleeping significantly earlier (median 0.63 [0.02–4.15] years in boys vs. 1.07 [0.04–8.96] in girls, position was preferred. p<0.02). Patients with congenital anomalies of the urinary tract and neurogenic bladder and In conclusion, massive night-time proteinuria post-Tx in a small child may mimic those requiring urological surgery prior to transplantation had an increased risk for fUTI. immunological mechanisms. The pathogenesis is presumed to be comparable to the Conclusion: fUTI is a frequent complication after pediatric renal transplantation, even in the mechanism of gross proteinuria in nutcracker syndrome. late post transplant period. Especially girls and children with congenital anomalies, neurogenic bladder and surgery prior to transplantation are at increased risk. Antibiotic prophylaxis, early diagnosis and consequent treatment of fUTI after pediatric renal transplantation are important prognostic factors for the long term transplant outcome.

COD. PP 203 COD. PP 204 Tacrolimus toxicity in paediatric renal transplant recipients Pre-renal transplantation radiological investigations of the vascular J Y Kausman, B Patel, S D Marks anatomy in children Great Ormond Street Hospital for Children NHS Trust , Department of Paediatric M G Meister, R D Bruyn, O Olsen, S D Marks Nephrology, Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street , Great Ormond Street Hospital for Children NHS Trust , Department of Paediatric WC1N 3JH London , England UK Nephrology, Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street , WC1N 3JH London , England UK Aims/Methods: We investigated if paediatric patients receiving oral tacrolimus for renal transplantation were experiencing drug toxicity as a result of excessive dosing within the AIM: Thrombosis, narrowing and anomalies of inferior vena cava (IVC) and iliac veins first three weeks post-transplantation when commenced on a standard dose of 0.3mg/kg/day (IV) can influence the surgical technique for renal transplant (RTx) surgery. At ou r in two divided doses, which was titrated to target 12-hour trough levels of 15ng/ml (with institution, all potential RTx recipients have imaging of their vascular anatomy, with most toxicity denoted as > 20ng/ml). cases investigated by Doppler ultrasonography (US). Magnetic resonance venography (MRV) is reserved to clarify US findings and investigate high-risk patients. The purpose of Results: 63 children (39 (62%) female) aged 1.9 - 17.7 (median 13.3) years underwent renal this study was to compare these modalities in the evaluation of the IVC and IV. transplantation with tacrolimus therapy as part of their immunosuppressive regimen. The ethnicity was recorded with 43 (68%) recipients Caucasian, 9 (15%) of Asian origin, 7 METHODS: Retrospective review and correlation of imaging and operative findings of (11%) of Middle East origin and 4 (6%) Afro-Caribbean. 41 (65%) patients had evidence o f patients undergoing RTx surgery, who have had both US and MRV examinations to tacrolimus toxicity with at least one toxic trough level with high levels in 15% (84 of 570) evaluate their vascular anatomy. of all samples. 49% (41 of 84) of toxic levels occurred in days 2-4 post-transplantation. Tacrolimus toxicity occurred in older children (p = 0.01) of increased height (p = 0.03) and RESULTS: Twenty-nine children (aged 1 to 18 years (median 12 years), 19 female) were body surface area (p = 0.046), with a tendency to occur in children of increased weight (p = investigated over five years. Twenty-one had subsequent RTx surgery (8 deceased and 13 0.06) in renal failure. There was no statistical difference in toxicity between different sexes, living related donor transplants). Normal anatomy on US and MRV in 17 (confirmed in 12 ethnicity, acute rejection rates or estimated glomerular filtration rates. at operation, 5 await RTx). Technically difficult US examination needing MRV fo r clarification in 6 (21%). Abnormal MRV and US correlation in 1 (3%). Normal US and Conclusions: This data suggests that the initial dose of tacrolimus was excessive for older technically inadequate MRV in 2 (7%). Normal US with anatomical variation on MRV in 3 patients and that dosing on a per kilogram basis should be capped at a maximum dose of (10%). The anatomical variations included left sided IVC, aberrant right common femoral 20mg/day and then titrated with diligent daily trough levels, especially in the first four days vein (CFV) and left IV partly drains into the azygos and left renal vein. after paediatric renal transplantation. CONCLUSION: US is a useful screening tool for the evaluation of vascular anatomy patency in children. US has a higher technical failure rate (21%), needing MRV for clarification, which is superior in delineating anatomical variants.

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COD. PP 205 COD. PP 206 PAGE KIDNEY IN PEDIATRIC RENAL TRANSPLANTATION : A PHARMACOGENETICS AFFECTS TACROLIMUS UNUSUAL CAUSE OF ACUTE RENAL FAILURE PHARMACOKINETICS AND PHARMACODINAMICS AFTER E Balzamo, S Cohen, S Krid, O Boyer, C Dheu, S Emond, F Sauvat, MF Gagnadoux, R KIDNEY TRANSPLANTATION (TX) IN A TIME-DEPENDENT Salomon, P Niaudet FASHION. A PILOT STUDY IN ADOLESCENTS Service de Néphrologie Pédiatrique, Hôpital Necker-Enfants Malades , 149 rue de Sèvres , S Tirelli, L Ghio, W Xiaochuan, M Ferraresso, V Martina, E Meregalli, C Mattiello, A 75015 Paris , France Edefonti Unit of Pediatric Nephrology , Via Commenda 9 , 20122 Milan , Italy A 11 year old girl with rapidly progressive glomerulonephritis received a kidney transplan t from her mother. During surgery, a dissection of the allograft renal artery led to a prolonged CYP3A5 gene polymorphism influences several aspects of Tacrolimus (TAC) ischemia time. She was given IV heparin to prevent thrombosis. At day 2 post- pharmacokinetics, including blood concentration, dose requirement and dose-normalised transplantation, she had persistent anuria, high blood pressure and acute anemia. An concentration, of kidney Tx patients. We analyzed retrospectively, the correlation between ultrasound and an CT scan showed a voluminous intrarenal haematoma at the upper pole. A CYP3A5 gene polymorphism and TAC pharmacokinetic parameters obtained 1, 2 weeks surgical drainage allowed a good revascularization of the kidney and plasma creatinine and 1, 3, 6, 12 months post Tx in 26 adolescents (mean age 15,8 ± 7,8 yrs). rapidly decreased. Two years later, serum creatinine was 102µmol/L. A 12 year old girl TAC initial dose was 0,2 mg/kg, aiming at a C0 level 10-20 ng/ml for the first 2 months with steroid-resistant FSGS received a kidney transplant from her mother with good early post Tx and 5-10 ng/ml thereafter. graft function. She was given prophylactic anticoagulation with enoxaparin and anti-Xa CYP3A5 genotype was determined by PCR, followed by direct sequence method. activity was 0.38. On day 3, she became anuric and hypertensive with acute anemia. During the first 3 months post Tx homozygous (CYP3A5*3/*3) patients (7) showed a Ultrasound examination showed a intrarenal collection at the upper pole and CT-scan higher TAC blood concentration than heterozygous (CYP3A5*1/*3) ones (19): 13.4±6.07 confirmed an intra-renal hematoma. Surgical evacuation of the hematoma at day 7 was ng/ml vs 7.82±2.12 ng/ml at 1 month (p=0.015). Afterwards, TAC blood concentration was followed by immediate diuresis. Serum creatinine and blood pressure were normal on day similar in the two groups. This data depended on the significant reduction of the daily drug 30. dose to achieve the desired blood target: 0.13±0.06 mg/kg vs 0.23±0.11 mg/kg at 6 months Page in 1939 described an acute renal failure and severe hypertension in animals after (p=0.01). Dose-normalised TAC concentration (ng/ml/mg/kg) was significantly lower in wrapping both kidneys in cellophane and attributed the symptoms to hypoperfusion of the patients with CYP3A5*1/*3 throughout the entire period: 33±22.16 vs 71.12±37.81 at 2 kidneys. The voluminous hematoma in our patients resulted in acute hypoperfusion of the weeks (p=0.02); 35.4±12.9 vs 85.2±58.9 at 6 months (p=0.04). Also TAC bioavailability graft with severe hypertension and acute renal failure. Anticoagulation may have been a (dose/C0) was greatly affected, being lower in CYP3A5*3/*3 patients than in contributory factor to the spontaneous bleeding. Early drainage restored the blood flow in CYP3A5*1/*3 ones: 0.73±0.5 vs 1.79±.0.42 at 6 months (p=0.001). the allografts with rapid recovery of renal function. In conclusion, the pivotal role of CYP3A5 on TAC pharmacokinetics/pharmacodinamics is in favour of a pre-emptive screening of CYP3A5 polymorphisms to individualize initial TAC dose (lower in homozygous than in heterozygous adolescents) and achieve therapeutic target early after transplantation.

COD. PP 207 COD. PP 208 A history of renal transplantation: a single centre study of 300 children Renal transplantation in small children (below 12 kg) from 1973 to 2000 U B Berg, M. Herthelius, J Sandberg, G Ty dén Rukshana Shroff (1), Lesley Rees (1), Carol Hutchinson (1), Oswald N Fernando (2), Dept. of Pediatrics , Karolinska University Hospital Huddinge , 14186 Stockholm , Sweden Richard S Trompeter (1) Department of Nephrourology, Great Ormond Street Hospital for Children NHS Trust, London, UK (1) and Department of Transplantation, Royal Free From 1982 to 2005, 174 transplantations (tx) were performed in children below 16 years of Hospital, London, UK (2) age at Karolinska University Hospital Huddinge. 43 (24 boys) of those transplantations Great Ormond Street Hospital for Children NHS Trust , Vascular Physiology Unit, 34 Grea t were done in children with a body weight <12 kg. Their median age was 1.4 (range 0.4-3.7) Ormond Street , WC1N 3JH London , UK years, body weight 9.4 (3.4-11.5) kg and height SDS –2.5 (-10.0-0.3). 65 % had preoperative dialysis. 79% received grafts from living donors (LD). The underlying diseases Methods: Patient and transplant survival and influencing factors were reviewed in the 300 were congenital in 38 (88%), obstructive uropathies in 12 (10 urethral valves), dysplastic children who received a renal transplant in our unit between 1973 and 2000, and in whom kidneys without obstruction in 5, congenital nephrotic syndrome in 12, Drash syndrome in we had a minimum follow-up of 2.5 years. 5, others in 4 and 5 had acquired diseases. Between 1982 and 1992, 4 children died, 2 because of generalized CMV infections (before Results: Median (range) age at transplantation was 10.3 (1.4 to 17.9) years. Forty-four the prophylaxis era) and 2 after graft loss. After 1992 only one child has died (recurrent percent had renal dysplasia. Forty-six children required a second and eight a third transplant HUS). After 1992, patient survival was 96.6% and graft survival 92% after 5, 10 and 15 before transfer to an adult unit. Overall patient survival at 5, 10 and 20 years was 97%, 94% years. Patient and graft survival were significantly better in children below 12 kg than those and 72% respectively. In the overall cohort age at transplantation did not affect mortality, above 12 kg at tx. Catch-up growth was seen during the first years after transplantation from but those transplanted before 5 years of age had a significantly shorter survival time post- mean height SDS of -2.95 at tx to –0.92 5 years after tx. Thereafter no further increase in transplantation (5.1 vs 19.1 years, p<0.0001). height was seen. Mean GFR (clearance of inulin) was 75±28 ml/min per 1.73 m2 one year after tx, 53±22 5 years after and 45±14 10 and 15 years after tx. Transplant survival (first transplant) for deceased donor and LRDs was 66% and 87% at 5 We conclude that renal transplantation can be performed with excellent short and long-term years (p<0.01), 51% and 54% at 10 years and 36% at 20 years (deceased donor transplants results also in very small children. only), and this pattern of improved graft survival for the first 5 years was also reflected in those transplanted between 1990- 2000 (Figure 1). In the overall cohort children <5 years and between 14-18 years age had a significantly worse outcome compared to those aged 6- 13 years: the median 5-year transplant survival was 66%, 73% and 63% in the <5, 6-13 and 14-18 year age groups respectively. However, amongst those transplanted in the last 10- years (1990 - 2000), age at transplantation did not affect outcome: the 5-year graft survival was 64% vs 67% and 10-year graft survival was 61% vs 58% in children <5-years vs >5- years age at transplant.

Conclusions: The outlook for successful transplantation is improving, and in the last decade was unaffected by the age at transplantation. The survival of LRD transplants is superior to deceased donor transplants for the first 5 years.

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COD. PP 209 COD. PP 210 VITAMIN D DEFICIENCY IN PEDIATRIC KIDNEY TRANSPLANT PHARMACOKINETICS AND IMMUNODYNAMICS OF RECIPIENTS BASILIXIMAB IN PEDIATRIC RENAL TRANSPLANT G Ariceta (presenting author) M Aguirre MI Vega C Uria RECIPIENTS UNDER CsA, MMF AND CORTICOSTEROIDS Hospital Cruces , Seccion Nefrologia Pediatrica. P/ Cruces sn , 48903 Barakaldo , Vizcaya Höcker B1, Kovarik JM2, Offner GF3, Zimmerhackl LB4; Jungraithmayr, TC4, Koepf S1, Spain Weber LT1, Hoppe B5, Plank C6, Daniel V7, Tönshoff B1 1University Children`s Hospital, Heidelberg, Germany; 2Novartis Pharma AG, Basle, Switzerland; 3University Children`s Vitamin D deficiency (reduced 25OHD) leading to HyperPTH is described in adults with Hospital, Hanover, Germany; 4University Children`s Hospital, Innsbruck, Austria; kidney transplant (Tx). Studies are lacking in children. 5University Children`s Hospital, Cologne, Germany; 6University Children`s Hospital, Erlangen, Germany; 7Institute of Immunology, Heidelberg, Germany Aim: to determine Vitamin D deficiency seasonal prevalence in pediatric kidney Tx University Children`s Hospital , Division of Pediatric Nephrology, Im Neuenheimer Feld 153 , D-69120 Heidelberg , Germany Design: cross-sectional study In a prospective, randomized, multicenter, placebo-controlled study, basiliximab Population: 30 kidney Tx (9 girls,21 boys), 14.2 ±5.3 years, in wintertime. Primary disease: pharmacokinetics/immunodynamics were evaluated in 42 resp. 69 pediatric renal transplant structural nephropathy 30%, glomerulopathy 28%, obstructive uropathy 13%, reflux 10%, recipients under CsA, MMF and corticosteroids. Patients weighing <35/ Q35 kg received 10 HUS 10%, others 10%. Previous dialysis: 57% during 0.8y (range 0.1-3y). First Tx: 24 (80%), second Tx, 6(20%). Years since Tx: 4.3y (range 0.25-12.5). Hypertension: 47%. mg/20 mg of basiliximab on days 0 and 4. Basiliximab concentration and CD25+/CD122+- MMF+calcineurin inhibitor: 90% (48% plus prednisone), others 10%. None was receiving T cell count were analyzed by ELISA and flow cytometry, respectively. Vitamin D. Distribution volume and basiliximab clearance were lower in children than in adolescents, but overall exposure was similar in both age groups because children’s lower dose allowed Results: CCr 89.6 ml/min/1.73 m2(range 46-123), 17 (57%) CCr >90, 11(37%) CCr 60-90, for their slower clearance and smaller distribution volume in comparison with adolescents. 2(6%) CCr 30-60. Ca 9.75±0.6 (Ca++ 4.99±0.3), P 4.2±0.8, Mg 1.78±0.7 mg/dl. 25OHD: Basiliximab clearance was lower in children and significantly reduced in adolescents on 18.8 ng/ml (range 6-42.7). Severe deficiency <5 ng/ml (n=1; 3%), moderate deficiency 5-15 MMF, compared with the same age groups of a former study without MMF, leading to a ng/ml, (n=10; 30%), insufficiency 16-30 ng/ml (n=12;40%), normal >30 ng/ml, (n=6; 20%). longer CD25 saturation than in the previous study (46±21 vs. 36±14 days). CD122 was 1,25-OH2D: 34 pg/ml (range 4-67). 2 patients (7%) 1,25-OH2D deficient. PTH: 58.8 pg/ml downregulated similarly in the basiliximab and placebo groups, indicating that (range 12.4-255). HyperPTH 33%. 25OHD correlated inversely with PTH (r = -0.42, downregulation resulted from concomitant immunosuppression with CsA rather than basiliximab. Conclusions: In pediatric patients, concomitant immunosuppression with MMF p=0.03), but directly with Phosphate (p=0.03) and 1,25-OH2D (p=0.047). We did not observe any relationship between 25OHD, Ca, Ca++ , Mg, CCr or years since Tx. causes basiliximab clearance reduction and CD25 saturation duration prolongation, possibly by anti-isotype antibody reduction. CD122 expression downregulation is due to the effect of Comments: The high prevalence of vitamin D deficiency in nearly ¾ of children in this CsA rather than basiliximab. series suggests Vitamin D should be carefully monitored in pediatric kidney Tx. Long term relationships with excess cardiovascular risk and increased adverse immune function should This study was supported by Novartis Pharma. be avoided through vitamin D supplementation to this vulnerable population.

COD. PP 211 COD. PP 212 SIROLIMUS-BASED IMMUNOSUPPRESSION VS. CNI Association between heat-shock-protein (HSP)70 and toll-like-receptor MINIMIZATION IN PEDIATRIC PATIENTS WITH CNI-INDUCED (TLR) 4 polymorphisms in renal transplantation NEPHROTOXICITY: 2-YEAR DATA 1Banki NF, 1Fekete A, 2O Viklický, 3Hubá èek JA, 1Rusai K, 2Vítko S, 1Tulassay T, Britta Höcker1, Anne-Kathrin Pieper2, Reinhard Feneberg1, Rüdiger Waldherr3, Elke 4Heemann U, 1AJ Szabó 1Gy Reusz 1 1 st Department of Pediatrics and Research Wühl1, Uwe Querfeld2, Burkhard Tönshoff1 1University Children’s Hospital Heidelberg, Laboratory of Paediatrics and Nephrology, Hungarian Academy of Sciences and Germany; 2Charité Children`s Hospital Berlin, Germany; 3Group Practice of Pathology Semmelweis University, Budapest, Hungary 2 Department of Nephrology and Transplant Heidelberg, Germany Centre, Institute of Clinical and Experimental Medicine Prague, Czech Republic 3 Center University Children`s Hospital , Division of Pediatric Nephrology, Im Neuenheimer Feld for Experimental Medicine of the Institute for Clinical and Experimental Medicine, Prague, 153 , D-69120 Heidelberg , Germany Czech Republic 4 Department of Nephrology and Transplantation, Technical University Munich, Munich, Germany In a 24-month case control study comprising 22 pediatric renal transplant recipients whose Semmelweis University , 1st. Department of Pediatrics, Bokay J u. 53-54 , 1083 Budapest , graft function declined due to biopsy-proven moderate/severe CNI-induced nephrotoxicity, Hungary we investigated the efficacy and safety of an SRL-based immunosuppression, combined with MMF and corticosteroids, vs. CNI minimization (-39±8.9%), over comparable posttransplant periods. Introduction: The long-term renal allograft outcome, which is influenced by Despite the SRL group’s lower baseline GFR and higher proteinuria, indicative of a more ischemia/reperfusion injury, has not improved significantly in the last decades. HSP70 pronounced CAN, graft function improved or stabilized after switch to SRL in a number of protects the kidney graft against ischemia and as an activator of TLR4, it takes part in the patients (12/13; 92%) comparable to that of the CNI minimization group (8/9; 89%). In both adaptive immune response. cohorts the median GFR increase after 1 year persisted in the 2nd year of observation. In Methods: We analyzed HSPA1A G(190)C, HSPA1B A(1267)G and TLR4 A(299)G patients exhibiting no borderline changes at study entry, switch to SRL was safe. Unde r polymorphisms with PCR-RFLP in the DNA of patients with well-functioning renal SRL treatment, 62% of patients developed hyperlipidemia; 38% needed erythropoietin allografts over 15 years (Tx15), consecutively transplanted recipients (Tx), patients with administration due to hypogenerative anemia. Proteinuria was aggravated in 46% of SRL- acute rejection (AR) and healthy, age-matched controls. treated patients. Conclusions: Both therapeutic strategies to combat CNI nephrotoxicity - Results : HSPA1B (1267)AA was less frequent in Tx vs. Tx15 (p=0.04) and vs. controls CNI withdrawal and SRL-based therapy or CNI dose reduction - led to a comparable (p=0.02). HSPA1B (1267)GG appeared more often in Tx vs. Tx15 (p=0.005) and vs. relative and absolute graft function improvement over a 2-year period. They should be controls (p=0.02). HSPA1B (1267)G allele occurred more frequent in Tx vs. Tx15 (p=0.03) compared in a prospective randomized study. and vs. controls (p=0.002). TLR4 (299)AG was less prevalent in Tx vs. Tx15 and the prevalence of TLR4 (299)G allele was decreased in Tx vs. Tx15. Conclusions: The increased prevalence of HSPA1B (1267)AA and TLR4 (299)AG genotypes in Tx15 indicates, that the better cell protective function of HSPA1B (1267)AA carriers and the decreased pro-inflammatory response in TLR4 (299)AG carriers might reduce acute rejections and thereby improve long-term renal allograft survival.

This work was supported by grants of OTKA F042563-F048842-T37578, ETT 208- 243/2003. A. F. and A. Sz. are reci pients of Bolyai scholarship.

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COD. PP 213 COD. PP 214 INTIMA-MEDIA THICKNESS AND CORONARY FLOW AUC guided dosing of cyclosporine in pediatric renal transplant RESERVE : NON-INVASIVE EVALUATION OF recipients HE BUNKER-WIERSMA *, JCMA DAVIN*, RP KOOPMANS#, JW GROOTHOFF*, ATHEROSCLEROSIS IN YOUNG ADULTS WITH RENAL TRANSPLANT PERFORMED IN THE PEDIATRIC AGE AH BOUTS*, HJM VAN KAN** *department of pediatric nephrology, Emma Childrens Vigano Sara Maria, Martina Valentina, Tomasoni Livio*, Turiel Maurizio*, De Blasio Hospital/AMC,Amsterdam #department of clinical pharmacology &, AMC,Amsterdam **department of clinical pharmacy, AMC, Amsterdam Giuseppe*, Delfino Luigi*, Cusi Daniele, Ghio Luciana and Edefonti Alberto Pediatric Nephrology Unit, "Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena" and * Emma Childrens Hospital/AMC , G8-252 meibergdreef 9 , po box 22700 Amsterdam , The Cardiology Unit, "R.Galeazzi Institute”, Milan, Italy Netherlands Unit of Pediatric Nephrology, Policlinico Foundation , Via Commenda 9 , 20122 Milan , Italy Introduction: The area under the curve (AUC) of cyclosporine is strongly related to the efficacy and toxicity of the drug and its variability is mainly determined by the absorption There are no data about the incidence of atherosclerotic disease in young adults who have phase. Close therapeutic drug monitoring (TDM) is warranted to optimize therapy, using been pediatric renal transplant recipients. Aim of this study was to evaluate atherosclerotic more appropriate methods to estimate the AUC than through concentration measurement. damage in coronary and carotid artery, using echocolorDoppler technique. We have We report the results of AUC guided therapeutic drug monitoring in 15 pediatric renal enrolled so far 18 patients (11 M, mean age 24.3 ±8.4 yrs); mean creatinine clearance 73 transplant recipients. ±24 ml/min/1.73 sqm and post-transplant FU 89.4±72.8 months, 14/18 patients were Methods: Blood samples were drawn just before and two hours after ingestion. Bayesian, hypertensive, no one was either hypercolesterolemic or diabetic. We studied the coronary model based estimation of AUC values was performed after each out-patient visit or during hospital admission. Calculated pharmacokinetic parameters, treatment efficacy data and flow velocity on the left anterior descending coronary artery by transthoracic echocardiography, before and after dipyridamole (0.56 mg/kg in 4` + 0,28 mg/kg in the next side effects were collected. Target AUC values were 5400 ng•h/ml in the first three months 2`). In Doppler signal we assessed the systolic and diastolic components and the coronary after transplantation and 3250 ng•h/ml after three months. flow reserve (CFR), which is a reliable index of coronary stenosis. We also measured the Results: 15 patients were evaluated, divided in two groups (group I: < 3 months after intima-media thickness (IMT) on common carotids by echocolordoppler, as an earlier index transplantation; group II > 3 months after transplantation). In patients with trough of atherosclerosis. concentrations below the therapeutic range, 61.5% of AUCs were sufficiently high. We Only one patient had an episode of angina pectoris during echocardiography, later found a graft survival of 91% in the first year and 87% during the 18 months of the study. diagnosed as vasospasm with coronarography. The mean CFR and IMT were 2.8 (range 50% of all patients reported at least one side effect. 1.6-4) and 0.5±0.07 mm, comparable to those of healthy subjects. However, the CFR was Conclusion: AUC guided monitoring of cyclosporine after kidney transplantation in abnormal in the 3 patients with the longer treatment period (dialysis + transplantation). children using C0 and C2 is valuable and leads to good graft survival rates. This method is There was a negative correlation between CFR and age and BMI (r= -0.36 and -0.46, not strictly dependent on a precise sampling time compared with C2 monitoring and may respectively p<0.005) facilitate the use of lower doses of cyclosporine In conclusion, young adults who underwent kidney transplantation in childhood require a specific screening program for the assessment of atherosclerosis and cardiovascular disease in order to prevent cardiovascular mortality.

COD. PP 215 COD. PP 216 Hyperuricemia following liver transplantation in children De novo membranous nephropathy in a young transplant recipient J Harambat1, L Dubourg2, B Ranchin1, A Liutkus1, M H Saïd1, O Boillot3, A Lachaux1, P SM Vigano, V Martina, E Meregalli, A Edefonti and L Ghio Cochat1 1 Département de Pédiatrie, 2 Service d’Exploration Fonctionnelle Rénale, 3 Unité Unit of Pediatric Nephrology, Policlinico Foundation , Via Commenda 9 , 20122 Milan , de Transplantation Hépatique, Hôpital Edouard Herriot & Université Claude Bernard - Italy Lyon, France , Departement de pédiatrie, Hôpital Edouard Herriot , 69437 Lyon , France The incidence of de novo membranous glomerulonephritis (MGN) in transplanted kidneys is around 1 to 2% and only few pediatric cases are described in the literature. Moreover, Uric acid may be involved in the development and progression of kidney disease. post-transplant de novo MGN may be associated with an increased risk of graft loss. Hyperuricemia is a common feature in adult liver transplant recipients but there is limited We describe a case of de novo post-transplant MGN in a child transplanted for ESRD from information in the paediatric population. In order to estimate the incidence, predictors and congenital renal hypodisplasia and severe vesicoureteral reflux. mechanisms of hyperuricemia in paediatric liver transplant recipients and to assess whether He is 7 years old and was transplanted in June 2004. The immunosuppressive regimen was hyperuricemia may impact GFR, we retrospectively reviewed baseline and follow-up data based on cyclosporine A, mycophenolate mofetil and corticosteroids. Three months after of 77 children who received a liver transplant between 1991 and 2005 (median follow-up transplantation he had a combined EBV and CMV infection and an acute rejection. The 6.3 [1.5-14.7] years). Renal function tests included plasma creatinine, protein and uric acid rejection was cured and the mycophenolate mofetil was discontinued. He had no other concentration, inulin and uric acid clearance. In the meantime, antihypertensive and complications until November 2005, when he developed a severe proteinuria (3 gr/24 immunosuppressive medications were collected longitudinally. hours), without other signs of renal transplant dysfunction, but with The cumulative incidence of hyperuricemia was 34% at 10 years post transplantation hypergammaglobulinemia and an EBV-DNA count of 250 copies/106 (normal value <40). (median time 2.8 years), mainly because of decreased urate tubular reabsorption. Factors A renal biopsy was performed and ACE inhibitors were administrated to reduce proteinuria significantly associated with an increased risk of hyperuricemia were older age, use of and the progression of renal damage. Membranous nephropathy was then diagnosted on cyclosporine as initial immunosuppression and the presence of an inborn error of renal biopsy. metabolism. After adjustment for donor and recipient age, gender, primary liver disease, A search for the main causes of secondary MGN was negative. postoperative acute renal failure, history of arterial hypertension, cyclosporine and The question whether MGN is idiopathic or EBV-related deserves further clarification. prednisone dose at one year post transplantation, hyperuricemia as time dependant variable was predictive (P 0.05) of chronic renal dysfunction defined as a GFR < 60 ml/min/1.73 m2. The control of serum urate concentration in 7/22 (32%) hyperuricemic patients eithe r by nutritional management or by allopurinol treatment tended to improve GFR (P 0.09). Hyperuricemia is a frequent problem after liver transplantation in children and should be considered a therapeutic target.

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COD. PP 217 COD. PP 218 Steroid-withdrawal in paediatric renal transplantation: 10 year Expression and activity of P-glycoprotein efflux pump in experience ly mphomonocytes of transplanted kidney subjects J Falger, GF Laube, MJ Kemper, TJ Neuhaus Nephrology Unit, University Children‘s G Conti, A Amore, L Bertola, S Turcato, E Ricotti*, M Messina **, G Segoloni**,R Coppo Hospital Zurich, Switzerland SC Nephrology Dialysis Transplantation, *Immunodiagnostic Lab, Regina Margherita , Kinderspital Zürich, Steinwiesstrasse 75, 8032 Zürich , 8032 Zürich , Schweiz Switzerland Hospital, Turin **Renal Transplantation Center, S.Giovanni Hospital, Turin, Italy University of Messina , Nephrology and Dialysis Unit , 98100 Messina , Italy Italy Background: Steroid-withdrawal (SW) after pediatric renal transplantation (TPL) is controversial as SW has been associated with increased risk of acute rejection. SW has been P-glycoprotein (P-gp) efflux pump plays a key role in protecting cells from xenobiotics, performed in our unit since 1995 following a selective protocol. Hypothesis: SW after TPL including immunosuppressive drugs. Therefore interest is being focused on P-gp activity in is safe and improves growth and blood pressure. Methods: Forty-seven of 56 patients renal transplanted patients (TX). We evaluated P-gp expression and activity in peripheral undergoing TPL between 1995 and 2004 could be followed. Immunosuppression included lymphomonocytes (PBMC) of TX. cyclosporin A, mycofenolate or azathioprine and steroids. Criteria for SW were: Time We investigated 34 patients, 3–39 years. Eleven were tested at transplantation (T0) and after interval after TPL Q1 year and no rejection episode for at least one year on steroid tapering. 7 (T7) and 30 days (T30); 12 patients (TX controls) with stable renal function (follow-up Results: SW was performed in 30 patients at a median time of 2.2 years post-TPL (range 5.9±3 years) were enrolled in a cross-sectional study; 11 patients were investigated after an 1.0–6.6). Only one patient experienced a steroid-sensitive rejection episode. Glomerular acute rejection (AR). Twenty healthy subjects were the control population. We evaluated P- filtration rate remained stable in both groups and there was a trend towards lower blood gp mRNA (RT-PCR, ratio GAPDH/mRNA), P-gp expression (FACS, percentage o f pressure in the SW-group. Growth was comparable in the two patient groups and in the positive PBMC), P-gp pump activity (active transport of the substrate 123-rhodamine after patients and their siblings. 60 min in FACS). Results: at SW (n=29) SW: + 3 months SW: currentlya Steroids (n=18): currentlyb Controls TX T0 TX T7 TX T30 TX controls GFR (ml/min/1.73m2) 82 (65–128) 86 (56–127) 82 (42–115) 70 (33–137) P-gp mRNA 0.31±0.12 0.46±0.2 0.46±0.2 0.55±0.28 0.15±0.14 Height (SDS) -1.1 (-4.0c – +1.8) -1.0 (-3.9c– +1.8) -0.8 (-4.6 c – +1.8) -0.8 (-2.3 – +0.5) % of P-gp pos PBMC 4.9±3.5 2.89±2 2.4±2.2 11.3±9* 4.2±2.5 BMI (SDS) +0.2 (-2.2 – +1.7) +0.2 (-2.0– +1.9) +0.1 (-1.7 –+ 1.8) -0.1 (-1.3 – +2.3) P-gp activity 29.6±7.7 22.1±12.4 29±8.7 36.3±8.6° 25.1±9.1 Hypertension: n (%) 15(52) 13(45) 11(38) 9(50) We observed a significant increase in P-gp expression (*p<0.05) and activity (° p<0.01) median (range); a 7.3 years (1.6-9.8) post-TPL. b 5.8 years (2.1-9.8) post-TPL. c patient after TX. P-gp mRNA expression increased significantly during AR (1.16±0.43, p<0.001) with multicentric osteolysis type III. and improved 30 days after recovery (0.75±0.38). Moreover, we detected the MDR1 exon 26 polymorphism (C3435T) in 28 TX. Wild-type (C/C) genotype was observed in 9 Conclusion: Selective steroid withdrawal was safe regarding renal function and acute patients, 11 were heterozygous (C/T) and 8 homozygous (T/T) for the mutation. No rejection. There was no substantial impact on height, BMI and blood pressure. difference in P-gp expression and activity was found for the different MDR1 genotype. Our data suggest the potential value of the P-gp detection in the evaluation follow-up of Tx.

COD. PP 219 COD. PP 220 Cyclosporine Monitoring and Clinical Outcome in the Early Post Registry of cytomegalovirus (CMV) infection and disease after pediatric Transplant Period in Children renal trans-plantation P Seikku, H Jalanko, C Holmberg R Feneberg, L T Weber, B Toenshoff University of Helsinki, Hospital for Children and Adolescents , Pediatric Nephrology and Univ. Children`s Hospital Heidelberg , Im Neuenheimer Feld 153 , 69123 Heidelberg , Transplantation , FIN-00029 HUS Helsinki , Finland Germany

Two-hour post-dose concentration (C2) correlates with cyclosporine (CsA) exposure and Chemoprophylaxis with ganciclovir or valganciclovir after pediatric kidney transplantation clinical outcome even in pediatric patients. We analyzed the data of 37 de novo pediatric is advisable in patients under high risk of developing CMV associated complications. It is renal transplantation (TX) patients (1.1 – 18.2 years of age). CsA was administered in three also in accordance with recently published „Best Practice Guidelines“ for adults. daily doses in patients with fast metabolism, otherwise two doses were used. CsA was Only GCV got a pediatric market authorization, while VGCV has none. Moreover, data on primarily monitored by through concentration (C0), aiming at 300 ìg/L early after TX. C2 efficacy and safety of VGCV are sparse until conclusion of the ongoing phase III study in between 1500 – 1800 ìg/L was considered appropriate. C0 and C2 target levels were pediatric patients. Available data suggest that VGCV has a considerable risk of dose related reached soon after TX but with much inter- and intraindividual variability. The eleven adverse drug reactions. Unfortunately, GCV is no longer available as an oral formulation. (30%) patients who experienced early acute rejection (AR) episodes had lower C2 than We suggest providing oral GCV prophylaxis (manufactured of i.v. GCV) for pediatric pa- those with no AR during 30 days (1284±513 vs. 1377±528 ìg/L; p=0.08) and 14 days tients <15 kg body weight, and oral VGCV for patients >15 kg body weight. VGCV use (1128±453 vs. 1390±543 ìg/L; p=0.0005) after TX. No rejection-free C2 threshold, or should be monitored by measurement of trough concentrations due to the higher risk of sufficient concomitant C0 and C2 levels, were defined, although higher C2 levels appeared toxic drug concentrations. Documentation of data on CMV chemoprophylaxis and the to be related to less rejection with no reduction in glomerular filtration rate (GFR=84±32 vs. clinical course of the patients is possible in the web based CMV registry platform 73±32 ml/min/1.73m2 in patients with C2>1500 and <1500 ìg/L , respectively, during 30 http://www.ped-tpl.org. Currently, the six participating centers included 26 patients. Thei r days after TX; p=ns). Graft histology three months after TX was not related to C2. C0 and mean trough ganciclovir concentration was 0.620.54 mg/L. In none of the patients C2 were not correlated, and C0 was not related to AR or GFR. In conclusion, high early C2 receiving VGCV or GCV chemo-prophylaxis severe adverse drug reactions were recorded. levels appear to be related to less AR without deterioration in GFR but more studies are Conclusion: Until VGCV is licensed for pediatric use, an interim strategy including needed before abandoning C0. Great inter- and intrapatient variability in C2, and dosing therapeu-tic drug monitoring of GCV concentrations is reasonable for chemoprophylaxis of interval of CsA, should be considered in defining target levels in children. CMV di-sease after pediatric renal transplantation. The internet based CMV registry provides the means for collecting data on CMV disease as well as the offer for free measurements of GCV concentrations for early detection of an overdose possibly resulting in adverse reactions.

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COD. PP 221 COD. PP 222 Web-based registry for cytomegalovirus (CMV) infection and disease MOR TALITY RISK FACTORS IN PEDIATRIC RENAL after pediatric renal transplantation TRANSPLANTATION. A ST UDY FROM THE FRENCH R Feneberg1, L T Weber2, M Oellerich3, B Toenshoff1 1 Univ. Children`s Hospital PEDIATRIC KIDNEY DATABASE. Heidelberg, 2 Univ. Children`s Hospital Munich, 3 Department of Clinical Chemistry, G Roussey E Allain-Launay G Guest B Ranchin A Maisin R Novo J Andre S Cloarec C University of Göttingen, Germany Guyot Univ. Children`s Hospital Heidelberg , Im Neuenheimer Feld 153 , 69123 Heidelberg , CHU Nantes , Quai Moncousu, Hopital Mère Enfant , 44093 Nantes , France Germany To assess post transplant patient survival in pediatric renal transplantation, we According to the “European Best Practice Guidelines”, chemoprophylaxis with ganciclovir retrospectively reviewed 554 transplants in 537 patients, registered from 1995 to 2005 in (GCV) or valganciclovir (VGCV) is advisable for patients after renal transplantation at high the French Pediatric kidney Transplantation database. risk for developing CMV-associated complications. While oral GCV is no longer available, a pediatric phase III study with VGCV is ongoing. Preliminary data suggest that Mean age at transplantation was 9.8 years (0.6 16.9); 17 children were transplanted before 2 prophylactic VGCV is effective in pediatric patients, but because of the 10-fold better oral years of age. 92% received a first graft. The graft was carried out respectively from a living bioavailability of VGCV, there may be a risk for dose-related adverse drug reactions such related donor (LRD) in 14% and from a deceased donor (DD) in 86% of the cases. A as leucopenia. We therefore set up the infrastructure for therapeutic drug monitoring (TDM) quadruple sequential immunosuppression was used of VGCV and an open-access web-based registry (http://www.ped-tpl.org) to document Seventeen patients (3.1%) died during the study period. Two deaths occurred after graft drug exposure, efficacy and safety. Results: VGCV was dosed according to the current failure (1 acute cholangitis, 1 gas embolism). Among the remaining 15,the two main causes recommendation: dose (mg) = 7 x body surface area (m²) x CrCL (ml/min/1.73 m²), up to a of death were: cancer/malignancy (3 Lymphoproliferative Disorder, 1 pleural sarcoma), and daily maximal dose of 900 mg. Because the risk for leucopenia increases at a GCV-AUC0- initial disease related complications (2 Schimke syndromes, 1 mitochondrial cytopathy, 1 24 > 60 mg x h/L corresponding to a 24 h trough concentration of 0.8 mg/L, and the trough methylmalonic acidemia). The other causes were : bacterial infections, unexplained sudden level correlates reasonably well with the corresponding AUC (r=0.69), a proportional deaths, suicide, drowning, and hyponatremia coma. VGCV dose reduction was recommended at a trough concentration >1.2 µg/ml. Currently, six participating centers included 26 patients. Their mean 24 h trough GCV plasma Patient survival at 1, 5 and 10 years post transplant was respectively 99%, 97% and 95%. concentration was 0.62 0.54 mg/L. In none of the pa-tients receiving VGCV or GCV Specific mortality rates were 1.3% and 3.5% for recipients of LRD and DD transplants chemoprophylaxis, severe adverse drug reactions were re-corded. Conclusion: This interim respectively. Death occurred at a median time of 1.9 years after transplantation. Long-term strategy including TDM of GCV concentrations and docu-mentation on the web-based patient survival was significantly lower in children less than 48 month-old at transplantation registry is a reasonable approach for successful chemoprophy-laxis of CMV disease in time (99%, 89%, 85% at 1, 5 and 10 years respectively versus 99%, 98%, and 96% for older pediatric renal transplant recipients. recipients, p<0.01). In this cohort, we observed a relatively low mortality rate. Improvement in managing immunosuppressive therapies may contribute to reduce mortality rate of pediatric renal transplantation.

COD. PP 223 COD. PP 224 BIOPSIES PROTOCOLE EXPERIENCE AFTER KIDNEY Improvement of GFR after switch to Certican and low-dose Ciclosporin TRANSPLANTATION IN CHILDREN A in children with Trans plant Nephropathy C Dheu, M Charbit, N Patey-Mariaud de Serre, G Guest, N Biebuyck, M.F Gagnadoux, O Pape L*, Ahlenstiel T, Ehrich JH, Offner G Gillion, R Salomon, P Niaudet Medical School of Hannover , Carl-Neuberg-Straße 1 , D-30625 Hannover , Germany Hôpital Necker-Enfants Malades, 149 rue de Sèvres , Département de Néphrologie Pédiatrique , 75015 Paris , France Background: Until now there have been no good therapeutic options in children with biopsy proven Transplant Nephropathy (TN) and loss of Glomerular Filtration Rate (GFR) while The prevalence of subclinical rejection is approximately 30% in the first three months in receiving Ciclosporin A (CsA); Mycophenolate Mofetil (MMF) and Prednisolone (Pred). renal transplant recipients. The relationship between the effects of early acute rejection and Method: In 13 kidney transplanted children (mean age 13 years SD 5) with chronic allograft nephropathy (CAN) is kwown. CAN and calcineurin-inhibitors CsA/MMF/Pred-immunosuppression, renal biopsy revealed significant TN. MMF was nephrotoxicity (CIN) are causes of late histological injury and ongoing decline in renal discontinued, CsA dose was reduced to 50% and Everolimus was started (1.6 mg/kg/d). function. Prednislone was stopped in 10/13 patients. Results: The mean GFR was 55 ml/min/1.73 m² (SD 24) 1 year before switch, 45 We analyzed the results of 26 graft biopsies performed at 3 and 12 months after renal ml/min/1.73m² (SD 16, p<0.05) at time of switch and 49 ml/min/1.73m² (SD 19, p < 0.05) transplantation in thirteen children. Baseline immunosuppressive treatment was 12 months later. There were no severe side-effects or acute rejections. LDH, Cholesterol, basiliximab, methylprednisolone, azathioprine and cyclosporin (CsA). These biopsies were CK and U-Albumine/Creatinine-ratio did not increase significantly. After 12 months the evaluated according to Banff criteria. mean Certican-C0-level was 4.0 µg/l (SD 1.5) and mean CsA-C0-level was 52 ng/ml (SD 23). At 3 months, 5 pts had normal biopsy, 5 pts had subclinical acute rejection ( 4 borderline Conclusion: The GFR of transplanted kidneys in children with TN improved by switching and one 1B), 3 pts had CAN associated with borderline acute rejection in 1pt or with CIN in immunospppression from CsA/MMF/Pred to Everolimus and low-dose CsA. 1 pt . CIN was observed in 3 pts (with CsA levels in normal range). None of these 8 pts with histological anomalies had clinical or biological overt graft dysfunction. Subclinical acute rejection was treated with 3 pulses of methylprednisolone and CsA was switched to tacrolimus. For the 3 pts with nephrotoxicity, CsA dosage was reduced and azathioprine was switched to mycophenolate mofetil. For the pts with CAN, azathioprine was switched to mycophenolate mofetil. At 12 months, pts who experienced early subclinical acute rejection had normal biopsy (2 pts), CAN 1 (2 pts), CIN (1pt).

These results showed that early protocol renal biopsies was superior to functional surveillance (clinical and biological) for the diagnosis and monitoring of acute rejection, CAN, and CIN and for adaptation of immunosuppression in the majority of our pts.

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COD. PP 225 COD. PP 226 Superior long-term graft function and better growth of grafts in Practical GFR measurements in kidney transplanted children using children receiving kidneys from pediatric compared to adult donors either a scintillation probe or the Schwartz formula - comparison with Pape L1*, Becker T2, Ehrich JHH1, Neipp M², Ahlenstiel T1,Offner G1 1 Department of findings based on the Sapirstein method as a gold standard Pediatric Nephrology, Medical School of Hannover, Germany 2 Department of Transplant Pape L1*, Ehrich JHH 1, Berding G2, Geisler S2, Offner G1, Lühr A2, Knapp WH2, Surgery Medical School of Hannover, Germany Berding G2 1 Department of Pediatric Nephrology, Medical School of Hannover, Germany Medical School of Hannover , Carl-Neuberg-Straße 1 , D-30625 Hannover , Germany 2 Department of Nuclear Medicine, Medical School of Hannover, Germany Medical School of Hannover , Carl-Neuberg-Straße 1 , D-30625 Hannover , Germany Organs from pediatric donors are often not accepted for pediatric recipients because previous reports suggested inferior graft function for small kidneys transplanted in children. The purpose of this study was to evaluate the accuracy of two different procedures to On the other hand studies have shown that kidneys of adult donors transplanted into measure the glomerular filtration rate (GFR) in children after kidney transplantation. children donwregulate filtration after transplantation and may not increase their function to 80 children after kidney transplantation (NTX) were evaluated. After i.v. injection of 80 the need of the growing child. kBq Cr-51-EDTA per kg body weight time activity curves were registered for 1 h. We assessed 64 male and 35 female (total n=99) white children aged younger than 10 years Additionally blood samples were obtained at 5, 10, 15, 25, 60 and 120-min post injection. (male: mean 5.1 years, SD 2.8; female: mean 5.8 years, SD 3.4) who had received cadaveric The GFR was calculated according to the Oberhausen method (OM) (including the 60-min kidney transplants at our centre between 1990 and 2005. Mean observation time was 5.9 blood measurement) and Sapirstein Method (SM). Based on plasma creatinine, GRF was years, SD 4.0. The children were divided into two groups depending on the kidney donor calculated according to the Schwartz formula (SF) (GFR = body height k / creatinine) age: 63 children (mean age 5.0 years, SD 2.9) received an organ of an adult, and 39 (mean using a k-value of 38. The degree of impairment in GFR was classified as low (60-90), age 6.4 years, SD 3.4) of a pediatric donor. Immunosuppression was performed with intermediate (30-60) or high (< 30 ml/min/1,73qm) Prednisolone, Cyclosporin A microemulsion ± Mycophenolate Mofetil. No significant differences in mean values of GFR obtained according to OM (49±20 Three to five years after transplantation the calculated GFR corrected to body surface was ml/min/1,73qm), SF (50±17) and SM (50±22) were observed (t-test). However, significantly higher in recipients of pediatric organs. The size of pediatric grafts doubled in measurements obtained according to OM showed a higher degree of correlation to SM the first years after transplantation while adult grafts had a stable size. Graft survival was compared to SF (r-square: 0.66 vs. 0.56). The tables of contingency revealed a higher comparable in both groups during observation time. correspondence in the degree of impaired kidney function between OM and SM (50 of 80 We conclude that pediatric donor kidneys should be given preferentially to pediatric cases) than SF and SM (44 of 80 cases). OM understimated the degree of impairment less recipients due to better long term function. frequently than SM (13 vs. 20 cases). All methods demonstrate an intermediate degree of impaired kidney function in a group of kidney transplanted children. OM method basing on measurement with a scintillation probe showed a higher correspondence to SM than values obtained with SF. OM method is superior for simple individual assessment of kidney function in children after KTX.

COD. PP 227 COD. PP 228 SUCCESSFUL ABO INCOMPATIBLE KIDNEY Recurrent Focal Segmental Glomerulosclerosis post renal TRANSPLANTATION OF AN 8-YR -OLD GIRL AND A 13-YR-OLD transplantation;`The Irish Experience` BOY O`Connell,M.Conlon,P. Gill,D. Hickey,D. Little,D Waldron,M. and Awan,A. T Ahlenstiel1, G Offner1, J Strehlau1, L Pape1, K Froede1, JHH Ehrich1, A Schwarz2, HG National Paediatric Transplant Centre , Childrens University Hospital, Temple Street , D 1 Heuft3, J Klempnauer4 1 Department of Pediatric Nephrology, Medical School of Dublin 1 , Ireland Hannover, Germany 2 Department of Nephrology, Medical School of Hannover, Germany 3 Department of Transfusion Medicine, Medical School of Hannover, Germany 4 Introduction Department of Transplant Surgery Medical School of Hannover, Germany The incidence of focal segmental glomerulosclerosis( FSGS) as a primary disease leading to Medical School of Hannover , Carl-Neuberg-Straße 1 , D-30625 Hannover , Germany end-stage renal failure (ESRF) and transplantation in children is reported to be between 7%- 9% with recurrence rates ranging between 30% and 40%.Various immunosuppressive Two children urgently needed kidney transplantation (KTx) because of technical failure of therapies with or without combination of plasma exchange (P.E.) are described in the hemodialysis and peritoneal dialysis. The parents were ABO blood group-incompatible. literature to treat post transplant FSGS. We decided to perform the first two ABO incompatible KTx in children in Germany: In September 2004 an 8-yr-old girl with syndromic focal segmental glomerulosclerosis Aim received a paternal kidney with donor/recipient constellation A1B/B (case 1), and in July We report the Irish data of the incidence of children with FSGS recurrence rates post 2005 a paternal kidney with donor/recipient constellation A2/0 was transplanted in a 13-yr- transplant and outcomes. old boy with autosomal-recessive polycystic kidney disease (case 2). Rituximab (375 mg/m2) was administered 2-4 weeks before the first immunoadsorption. Patients and Methods Immunosuppression (tacrolimus, mycophenolate mofetil, prednisolone) was started just Retrospective analysis of paediatric patients with FSGS transplanted in Ireland between before the first apheresis. Initial tacrolimus levels were targeted between 15-20 ng/ml. 1998 and 2006. During the last pre-transplant week, 5-6 antigen-specific immunoadsorptions (Glycosorb® There were a total of 76 paediatric transplants in Ireland between 1998 and 2006 ,7 patients ABO A-column) were applied to remove anti A-antibodies. Intravenous immunoglobulin had FSGS and were transplanted in this period (9.2 %). was administered preoperatively. After KTx, further immunoadsorptions were performe d All children were Irish and Caucasian. during the first 2 weeks. Recurrence of FSGS with marked proteinuria (>2 gram/L) occurred in 6 patients within 24 Before KTx, antibodies against paternal erythrocytes (20°C) were reduced from titer 64 hours post transplantation (case 1) and 32 (case 2) to titer 4 by 5-6 antigen-specific immunoadsorptions. During initial post-transplant period, the girl was treated with 3 immunoadsorptions to maintain the Results antibody titer below 8. In contrast the boy needed 5 post-transplant immunoadsorptions The patients are separated into 2 groups- because of antibody rebounds up to 64, last on day +12. No side effects of Group 1 who received plasma exchange within 24 hours of onset of proteinuria and Group 2 immunoadsorption were observed. After the first postoperative month further increases in who received it later than the 24 hour period. antibody titer resolved spontaneously. Both children had an excellent initial graft function. Patients in group 1 have complete and sustained remission 11 and 18 months post Two weeks and one year after KTx, graft biopsies showed no signs of acute rejection apart transplantation. Patients in group 2 had marked reduction in proteinuria but complete from positiveness of C4d. The renal function of both patients was stable with serum- remission was not achieved. creatinine of 125 µmol/l 17 months after KTx and 85 µmol/l 7 months after KTx, respectively. Conclusion ABO incompatible KTx using antigen-specific immunoadsorption and rituximab may serve Recurrence of FSGS post transplantation remains a challenging task for transplant teams. as a suitable alternative for children urgently needing KTx and missing an ABO compatible Various treatment combinations have been tried with different results. The most promising donor. of them seems to be early plasma exchange therapy. Risk factors for recurrence of FSGS described in literature were no different in our patient cohort.

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COD. PP 229 COD. PP 230 Nephrocalcinosis in the renal allograft: prevalence and risk factors? Dense B-cell infiltrates in paediatric renal transplant biopsies are Habbig S Licht C Stapenhorst L Beck B Wolf M Deven ge J Hoppe B predictive of renal allograft loss. Division of Pediatric Nephrology , Department of Pediatrics, University Children´s MR Muorah 1,2 PA Brogan 1,2 RS Trompeter 1 NJ Sebire 1 SD Marks 1 1 Renal Unit, Hospital , 50924 Cologne , Germany Great Ormond Street Hospital for Sick Children, London, UK 2 Institute of Child Health, University College London, UK Nephrocalcinosis (NC) is a known complication after kidney transplantation (KTx) in adult c/o Dr Stephen Marks, Consultant Paediatric Nephrologist , Renal Unit, Great Ormond patients with a reported prevalence ranging from 2 to 18%. Persistent hyperparathyroidism Street Hospital for Children NHS Trust, Great Ormond Street , WC1N 3JH London , UK and hypercalcemia are said to be the main culprit. However, only limited data concerning pediatric KTx recipients are available. We had observed hypocitraturia in the majority o f Background: A previous single study has suggested adverse outcome for renal allograft children after KTx and speculated this to be due to the tubulotoxic effect of calcineurin rejection associated with dense CD20 lymphocyte infiltrates. Aims: To further investigate inhibitor treatment. the relationship between renal allograft survival and CD20 positive lymphocyte infiltrates in As hypocitraturia is one of the main risk factors for NC we now screened the KTx biopsy renal transplant biopsies from children with graft dysfunction. Results: 50 transplant findings (between 2000 and 2006) of 43 pediatric transplant recipients for NC and biopsies were performed for investigation of acute or chronic allograft dysfunction in 48 correlated the data with urinary excretion of lithogenic (oxalate, calcium) and of stone children of median age 13.1 (range 2.1-17.5) years, at 22 (0 – 155) months post- inhibitory substances (citrate), the latter differentiated according to immunsuppressive transplantation. Median follow up was 24 months (range 0 – 62) post-biopsy. 17/50 (35%) regimens. graft losses occurred at 8 (0 – 36) months post-biopsy, and 49 (1 – 163) months post- Biopsy findings revealed NC in 3 male patients (7%). Hypocitraturia was found in all (0.25, transplantation. There was increased graft loss in those with dense (> 300 cells per high 0.7 and 1.49 mmol/1.73m2/24h, normal>1.9) and hyperoxaluria in one patient (0.69 power field (hpf)) CD20+ lymphocyte infiltrates (15/50 patients) at follow up (p < 0.05;see mmol/1.73m2/24h, normal<0.5). Overall, hypocitraturia was found in 64% and figure). Dense B-cell infiltrates were also associated with increased glucocorticoid hyperoxaluria in 40% of our KTx recipients. Although PTH was elevated in 50% of the requirement to acute treat rejection (p < 0.05), and estimated GFR was significantly lower patients, hypercalciuria was not detected. Neither NC nor hypocitraturia were correlated to a at follow up in those with dense CD20 infiltrates. There were no significant differences in certain immunosuppressive regimen. Calcineurin inhibitor toxicity was not observed in any age, sex, EBV or CMV viral loads or baseline immunosuppressive regimens between those NC-patient; however, tubular atrophy was present in all NC-patients but in 70% of the non with dense CD20 infiltrates and those with fewer CD20 infiltrates. Conclusions: We NC-patients. confirm the previous suggestion that demonstration of dense CD20 lymphocyte infiltrates in We conclude, that NC is a frequent complication in pediatric KTx recipients. We consider renal transplant biopsies is associated with adverse clinical outcome. Dense CD20 hypocitraturia to be the main risk factor for NC and hence suggest a prophylactic treatment lymphocyte infiltrates could be an important factor in stratifying patients with rejection as with alkaline citrate. high risk for renal allograft loss, thereby necessitating more intensive therapy. B-cell depletion therapy with rituximab may be worthy of further study in this clinical context

COD. PP 231 COD. PP 232 Life threatening sirolimus neurotoxicity due to concomitant Paediatric Renal Transplantation in Highly Sensitised Children - A clarithromycin treatment Novel Approach M Wigger, J Muscheites, E Drueckler, D Haffne r C Quinlan A Awan M Keogan D Gill M Waldrom UKJ Nephrologie , Rembrandtstr. 16/17 , 18057 Rostock , Germany The Children`s University Hospital, Temple Street , Renal Department , Dublin 1 Dublin 1 , Ireland Sirolimus is a promising alternative immunosuppressive drug in patients suffering from chronic transplant nephropathy, especially related to calcineurin inhibitors. Case report: In Highly sensitised children have markedly reduced chances of receiving a successful an adolescent girl the immunosuppressive regime was switched from tacrolimus to cadaveric renal transplant. We describe an inovative approach to desensitisation & share our sirolimus due to a severe biopsy proven chronic transplant nephropathy 11 years after renal experience both of the protocol & the outcomes of two patients. transplantation. Six months later she was started on clarithromycin medication because of an upper airway tract infection. Three days later she complained of severe abdominal pain Patient 1, a 13 year old girl, was diagnosed at 3 weeks of age with the Finnish variety of and nausea followed by recurrent vomiting and diarrhoea. Shortly thereafter the girl was nephrotic syndrome & subsequently had two organ rejection episodes, PRA1 of 95% admitted to our hospital because of progressive somnolence, trembling, and state o f confusion. At the time of admission sirolimus blood level was markedly increased with Patient 2, a 4 year old boy, with steroid resistant nephrotic syndrome diagnosed at 20 20.6µg/l (32 hours after last application). After exclusion of well known causes of acute months of age, found to have a PRA1 of 85% This was presumed to be a complication of neurological diseases, e.g. menigoencephalitis, diagnosis of sirolimus intoxication was multiple blood transfusions. made. After cessation of sirolimus the neurological symptoms completely deceased within 2 days. Conclusion: Interaction of sirolimus and other drugs being also metabolized by Both had some response to standard immunoglobulin (2g/kg IV) monthly for 3 months. We cytochrom P450 pathway (e.g. clarithromycin) may cause life threatening neurotoxicity. developed a protocol involving sequential therapies with rituximab, a chimeric anti-CD20 monoclonal antibody (375mg/m2) weekly for 4 weeks, followed by five plasma exchanges. Both patients also received standard immunosuppressant therapy, basiliximab, tacrolimus, mycophenolate mofetil & steroids. Further plasma exchange & immunoglobulin therapy were given pre & post operatively when anti-donor antibodies were detected.

Both patients received cadaveric renal transplants bearing HLA antigens to which they originally had antibodies, & which would have precluded treatment. In the case of patient 1, the graft kidney continues to function well 3 years post transplant. Unfortunately patient 2 has had one, biopsy-proven, rejection episode, treated with steroid pulses & IVIG. His biopsy shows 50% fibrosis, it seems likely he will require dialysis at some point in the future.

We describe a novel approach to desensitisation of highly sensitised children.

1580 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 233 COD. PP 234 Risks for Recurrent Focal Segmental Glomerulosclerosis (FSGS): A Identification of viral genome in renal biopsies of pediatric kidney Single City Experience trans plant recipients: a prospective study M Muorah 1,3 R Trompeter 1 C Reid 2 J Taylor 2 L Rees 1 1. Renal Unit, Great Ormond L Murer (1), M De Pieri (1), M Della Vella (1), L Barzon (2), M Pacenti (2), C Mengoli (2), Street Hospital for Sick Children, London, UK 2. Renal Unit, Evelina Children`s Hospital, C Carasi (1), G Montini (1), G Zacchello (1). (1) Department of Pediatrics and (2) Guys Hospital, London, UK 3. Institute of Child Health, University College London, UK Department of Histology, Microbiology, and Medical Biotechnologies, University of c/o Dr Stephen Marks, Consultant Paediatric Nephrologist , Renal Unit, Great Ormond Padova, Italy Street Hospital for Children NHS Trust, Great Ormond Street , WC1N 3JH London , UK Department of Pediatrics - University of Padua , Via Giustiniani 3 , 35128 Padua , Italy

Objectives: To investigate the risk factors for FSGS recurrence post transplantation. BK and ParvoB19 are associated to specific virus-related allograft nephropathy, but the role Methods: Retrospective case note review of all patients presenting over 22 years in two of viral infection in determining acute and chronic renal allograft rejection is still paediatric renal units with histologically and/or clinically proven FSGS recurrence in their controversial. We prospectively investigated the prevalence of viral sequences in kidney allograft. Results: There were 76 transplants in 57 children (30 boys) at a median age of biopsies obtained from a series of pediatric kidney-transplant recipients (age m.11,9+7,6 12.1 (4-18) years. Follow up was for 5.4 (0.5 – 20) years or until graft loss. One child had years; immunosoppression: basiliximab, steroids, FK506 or cyclosporinA±MMF). Control four transplants, three had three, ten had two and 43 had one. FSGS recurred in 23/76 iterative biopsies were performed at 6(N=68), 12(N=54) and 24(N=31) months post-tx; 11 (28.9%) overall: 17/57 (29.8%) first transplants and 3/4 (75%) second transplants (in those biopsies were performed because of acute renal dysfunction. DNA of EBV, CMV, HHV6, who lost the first to FSGS). In a more recent cohort since 2000, recurrence was noted in HHV8, BKV, and parvovirus B19 was searched by a sensitive real-time PCR and the results 10/16 (62.5%) first transplants. 7/57 (12.3%) children had familial FSGS (having another were correlated with histological results (Banff 97). Viral DNA was detected in 64%, 62% family member with FSGS and/or having NPHS2/NPHS1 mutations) and none developed and 60% of 6, 12, and 24 months biopsies, respectively and HHV6 and ParvoB19 were the recurrence. Age at transplant, deceased or live related donor, sex, mesangial proliferation on most prevalent viruses; the prevalence of viral genome was higher in the biopsies showing initial biopsy did not affect recurrence. Recurrence was diagnosed significantly higher in acute or chronic lesions (Banff III, IV,V) than in the normal histology cases (72%vs58%, patients who had bilateral nephrectomies (BNX) prior to transplantation 11/17 vs. 6/17 70%vs56% and 64%vs50% at 6,12,24 months, respectively) but without stastically (p<0.01). 15/16 from 2000 had BNX prior to transplantation. No increased rate of graft loss significancant difference; CrCl at 6,12,24 months was not significantly different between in patients with recurrence was detected. Conclusion: Recurrent FSGS remains a difficult patients with or without positive virological results. Viral-genomes were isolated in 7/11 clinical problem possibly occurring at an increasing rate. Postulated clinical risk factors for elective biopsies: 2 tubulo-intersitial nephropathy (BKV), 3 thrombotic microangiopathy recurrence largely vary between studies. Recurrence after BNX is more easily clinically and 1 acute vascular rejection (ParvoB19), and 2 acute rejection (EBV). Our data suggests diagnosed explaining perhaps the apparent higher rate but may also represent a group of that BKV and parvoB19 associated nephropathies are frequently responsible of acute renal patients who have had more aggressive primary disease dysfunction in kidney transplanted children, but further investigation is needed for better understanding the meaning of the high prevalence of viral genome isolation in iterative allograft biopsies.

COD. PP 235 COD. PP 236 Functional genetic polymorphisms eNOS 894G>T, MTR 2756 A>G and SECONDARY RENAL SCARRING IN TRANSPLANTS MTHFR 677C>T and renal survival in pediatric kidney transplant A Peco-Antic, M Kostic, Z Krstic, J Markovic-Lipkovski, D.Kruscic, D Vukanic, L Artifoni (1), S Negrisolo (1), S Centi (1), M Della Vella (1), G Ghirardo (1), M Cardillo B.Spasojevic, D.Paripovic, M.Stanic, Z Smoljanic (3), GM Ghiggeri (4), L Ghio (5), F Ginevri (4), F Perfumo (4), F Anglani (6), M University Children`s Hospital , Tirsova 10, Nephrology Department , 11000 Belgrade , Scalamogna (3), C Carasi (2), G Zacchello(2), L Murer(1-2) (1)Laboratory di Pediatric Serbia Serbia & Montenegro Nephrology, Department of Pediatrics Univ.of Padua, (2)Nephrology, Dialysis and Transplant Unit, Department of Pediatrics, Univ. of Padua (3)NITp Transplant Immunology Background: It has been assumed that children overgrow their sensitivity to renal scarring and Blood Bank, Maggiore Policlinico Hospital, Milan (4)Nephrology Unit, G. Gaslini after 4 years of age due to the maturation of the kidney. However, Coulthard et al showed in Children`s Hospital, Genoa, (5)Dialysis and Transplant Unit, De Marchi Pediatric Clinic, transplant and adult pig kidneys that the maturation of kidney is not crucial for the Milan (6)Department of Medical and Surgical Sciences, Laboratory of Molecular Biology, resistance to scarring. Univ. of Padua The aim: To look for reflux nephropathy in renal allograft from adult donors in pediatric Department of Pediatrics - University of Padua , Via Giustiniani 3 , 35128 Padua , Italy recipients. Methods: Pediatric transplant patients who had more than one urinary tract infection (UTI) The major cause of reduced long term renal survival in kidney transplant is the chronic after transplantation have been screened by dimercaptosuccinic acid (DMSA) scanning after allograft nephropathy, characterized by an atherosclerotic-like vasculopathy associated to at least a three-month infection–free interval. Patient with DMSA showing focal scarring risk factors as oxidative stress, nitric oxide (NO) production, and hyperhomocysteinemia. had voiding cystography (VUCG). Kidney biopsy was done in patient with renal scarring Functional polymorphisms of MTHFR and MTR genes are associated with increased levels and chronic graft dysfunction. of homocysteine, and a polymorphism of eNOS gene is associated with renal failure. Results: Forty three transplant patients were followed-up for more than two years. Eight of We performed a genetic analysis of polymorphisms eNOS 894G>T, MTR 2756 A>G, them (18.6%) had recurrent UTIs and renal scarring at DMSA scan. All of these patients MTHFR 677C>T and MTHFR 1298 A>C in the recipients (group R) and in the donors received adult kidney (7 from parents, 1 cadaver). VUCG showed vesicoureteral reflux (group D) of 269 pediatric kidney transplants, with a renal follow-up of 5-23 years. (VUR) in 62.5% patients with renal scarring. Renal biopsy revealed chronic pyelonephritis Comparing the genotype frequencies observed in the group of R/D with functional loss of in all biopsied patients (7). Outcome: two patients lost their graft function, two additional the transplanted organ (37) with those observed in the group R/D with functioning organ patients had chronic renal failure and four patients remained with normal renal function (207) we can state that: after successful instillation of Deflux paste or antibacterial prophylaxis. a) the donor MTR 2756AA genotype in the associates with the loss of the transplanted Conclusion: Healthy adult kidney is prone to developing reflux nephropathy when organ (P=0.036), transplanted with refluxing ureterocystoneostomia. Therefore, the prevention of allograft b) the donor MTHFR 677TT/1298AA genotype of the is more frequent in the group with reflux nephropathy requires non refluxing ureteric implantation or antibiotic prophylaxis. loss of the transplanted organ compared to the group with functioning organ. This Also, UTIs should be promptly treated in transplanted patients. difference nearly achieves statistically significance if compared with the group with an organ survival >=10 years, c) the donor MTR 2756AA/MTHFR 677TT genotype is more frequent in the group with loss of transplanted organ compared to the group with functioning organ. We hypothesize that functional polymorphisms of genes involved in homocystein metabolism in the donor genotype plays a role in the survival of the transplanted kidney. Pediatr Nephrol (2006) 21:1493–1635 1581

COD. PP 237 COD. PP 238 Unexpectedly high inter- and intra-patient variability of ganciclovir Echocardiographic changes in children after renal transplantation levels in children T Pennaforte, R Ben-Abdallah, A Lahoche, M Dehennault, R Novo, M Foulard J Vethamuthu, J Feber, A Chretien, D Lampe*, G Filler Division of Nephrology, Pediatric Nephrology, Jeanne de Flandre Hospital , CHU Lille , 59000 Lille , France Department of Pediatrics, Children’s Hospital of Eastern Ontario, Ottawa, K1H 8L1, Canada; and *Institute of Toxikology – Clinical Toxicology and Poison Control Center BACKGROUND: Chronic renal failure leads to cardiac structural and functional changes Berlin, BBGes, Berlin, 13437, Germany known as uremic cardiomyopathy. Renal transplantation should normalize cardiac Dept.of Pediatrics, Children`s Hospital of Eastern Ontario , 401 Smyth Rd. , K1H8L1 alterations by correction of uremic state; however, left ventricular hypertrophy (LVH) is Ottawa , Ontario Canada frequently found in children with a renal transplant and its long-term consequences are largely unknown. Background: Few studies have validated the current pediatric dosing recommendations OBJECTIVE: To assess the changes of left ventricular morphology after renal of oral Valganciclovir for Cytomegalovirus prophylaxis after transplantation using transplantation and to evaluate the effect of several risk factors on the trend of LVH. pharmacokinetic monitoring (PKM). METHODS: Transthoracic echocardiograms from 33 renal transplanted children were Methods: Single-center, retrospective study of all available Ganciclovir levels in investigated in a retrospective study at the time of surgery (mean age 9.8±3.5 years) and at transplanted children as well as anthropometric parameters and Cystatin C-based renal 3-years follow up. The left ventricular mass (LVM) index was assessed by indexing LVM function. Ganciclovir monitoring was performed by high-performance liquid to height. Univariate analysis was used to analyze the relationship between risks factors chromatography. For the normalization of dosing to GFR and target trough levels, we (anemia, arteriovenous fistula, hypertension and cyclosporine therapy) and LVH. assumed first-order kinetics. RESULTS: There was an increasing prevalence of LVH at follow up (40% vs 31%) but no Results: Using PKM, we analyzed 57 Ganciclovir levels (range 1-6/patient) in 20 significant difference in the mean values of LVM index (115±63 vs 103±55 g/m2, p=0.18). children (mean age 8.6±5.5 years) treated with intravenous or oral Ganciclovir, or oral Moreover, hypertension was higher (73 vs 65%) and correlated significantly with the Valganciclovir. Ganciclovir levels were drawn after IV therapy (n=9), during oral prevalence of LVH (38 vs 16%) and LVM index (126±65 vs 83±32, p<0.05). There was no Ganciclovir (n=5), or during oral Valganciclovir (n=15). Oral bioavailability of significant relationship between the prevalence of LVH or LVM index change and anemia, Valganciclovir was 42.0±21.8%. The dose-normalized intra-patient Valganciclovir arteriovenous fistula and cyclosporine therapy. variability was 83%. Mean GFR was 92±22 mL/min/1.73 m2. Mean Ganciclovir CONCLUSION: This finding clearly underlines that meticulous blood pressure control may concentration at last available measurement was 0.60±0.09 mg/L (therapeutic range 0.5- be beneficial for the maintenance of myocardial structure in children after renal 2.0 mg/L). Sub-therapeutic Ganciclovir levels on recommended IV doses were found in 8 transplantation. patients. This subset of patients was significantly younger (4.5±3.1 vs. 11.4±5.0 years). Sub-therapeutic levels (<0.5 mg/L) were found in 24/57 instances and 10 patients subsequently had their dose increased. The last Valganciclovir dose adjusted to a GFR of 100 mL/min/1.73 m2 was 842±323 mg/m2/day. Conclusion: A high proportion of patients had low Ganciclovir levels both on intravenous and oral therapy. The oral bioavailability of Valganciclovir was 42%. The majority of patients required dose increases in order to obtain levels >0.5 mg/L, and the substantial intra-patient variability warrants pharmacokinetic monitoring.

COD. PP 239 COD. PP 240 Vitamin supplementation reduces hiperhomocysteinemia in paediatric Solitary renal allografts from an infant donor successfully transplanted and young adults renal transplant recipients into siblings C Simao L Mendes A Cabral M Almeida C J Mache, P Vilits, S Roedl, I Marschitz, E Ring Departments of Pediatrics and Urology, Clínica Universitária de Pediatria; Hospital Santa Maria , Av. Prof. Egas Moniz , 1699 Medical University Graz, Austria Lisboa Cod Lisbon , Portugal Medical University of Graz , Department of Pediatrics, Auenbruggerplatz 30 , A - 8036 Graz , Styria Austria Introduction: Cardiovascular diseases (CVD) are the main causes of morbidity and mortality in kidney transplant recipients. Several epidemiologic prospective studies have Background. Kidneys from pediatric donors transplanted into the growing child show a provided that hiperhomocysteinemia (HHC) is a independent risk factor for CVD. Aim of better long-term functional adaptation than do adult-donor kidneys. The use of kidneys from our study was to document in hiperhomocysteinemic renal transplant recipients (RTR), very young donors - either en bloc or as single kidneys - has been discussed controversially. pediatrics and young adults (0-19 years), the efficacy and safeness of the combined folic Case reports. We report on two female siblings (ages 7 and 9 years, respectively) with end- acid (FA), vitamin B12 (B12) and vitamin B6 (B6) supplementation to decreases total stage renal failure due to autosomal recessive Alport syndrome. Both were HLA- homocysteine levels (tHc). identical,their blood groups were 0 and A, respectively. After 5 months on hemodialysis, an Methods: We investigated in 22 RTR baseline levels of HC and 12 of them presented HHC infant en bloc graft (11-month-old male donor, blood group 0, weight 9.6 kg, kidney length (tHc > 11,3 umol/l-ESPN 2002); 10 patients had normal levels. Patients with HHC received 6.6 / 6.7 cm) was offered to the younger girl. The en bloc graft was separated on the back the vitamin supplementation with FA – 5 mg/die; B12 – 500 ug/die; B6 – 40 mg/die. table and sequentially transplanted into both siblings. No further dialysis was needed. On Analytic measures were performed at baseline and 2, 6 months. immunosuppression with daclizumab, tacrolimus, mycophenolate mofetil, and steroids they Results: We observed a decrease in tHC levels in the treatment group (p< 0,001) after 6 experienced no acute rejection episode. Posttransplant proteinuria resolved after 4 and 7 months, without differences in the other group. There were no differences between the weeks, respectively. Within 8 months, the grafts grew to a length of 10.0 and 10.3 cm, groups in age, gender, hypertension, congenital or acquired renal disease. 56% of patients calculated relative GFR (Schwartz formula) rose to 111 and 125 mL/min/1.73m2BSA, with HHC had normal levels after supplementation. No side effects were detected. There respectively. was a significant correlation between basal creatinine and tHc level (p<0,01). Conclusions: Conclusion. Separation of an en bloc pair into solitary allografts was successful and both The supplementation with FA, B12 and B6 normalize tHc levels in more than 50% of recipients show a good short-term graft function. In selected cases, this approach may add patients , is safe and could improve the long term vascular prognosis of pediatric and young to expand the deceased donor pool. adults RTR. Further study with more patients will be useful. 1582 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 241 COD. PP 242 Cyclosporine twice or three times daily dosing in pediatric transplant EBV and BK virus PCR monitoring in kidney transplantation as a patients – It is not the same! guide line of immunosuppressive therapy. G Filler, V Rocha de Barros, JE Jagger, U Christians TQH Nguyen , C Azéma , M Rémésy , B Horen , C.Mengelle , S Decramer , F Bouissou Children`s Hospital of Eastern Ontario , 401 Smyth , K2H7M9 Ottawa , Ontario Canada Pediatric Nephrology, Hôpital des Enfants , 330 Avenue de Grande Bretagne TSA 70034 , 31059 Toulouse , HG France Not infrequently, physicians elect to divide micro-emulsified cyclosporine (CyA-ME) from twice daily (b.i.d.) to three times daily (t.i.d.) dosing in an effort to minimize toxicity. Immunosuppressive (IS) therapy in transplantation is mainly empiric. Over Equivalent exposure is assumed. Few studies have compared 24-hour pharmacokinetic (PK) immunosuppression leads to side effects, especially virus proliferation. Routinely virus profiles on both dosing regimes in the same patient. We retrospectively studied a PCR test was introduced in our protocol in 1998 for EBV and BK-JC virus. We report 12 heterogeneous population of 7 pediatric patients (one heart transplant, 5 renal transplant and children, out of 70 successive kidney transplantation, who experienced prolonged positive one FSGS patient) on both dosing regimes who had complete 24-hour PK profiles on CyA- blood PCR test for 7 EBV (4 reactivation, 3 primary infection) and 5 BK virus (3 proven ME. Four patients were converted from b.i.d. to t.i.d. and 3 patients from t.i.d. to b.i.d. BKV nephropathy) undergoing classical triple IS therapy (steroid/AZA or MMF/ CsA o r dosing. There was no difference in the dose/kg (5.66 ± 2.52 mg/kg on b.i.d. dosing and 5.75 FK). In these patients we prospectively decided to decrease the drug dosage, first anti ± 1.81 mg/kg on t.i.d. dosing, p= 0.8578, two-sided t-test). When comparing the dose- metabolite and second anticalcineurin, until a negative PCR test was obtained. The lowering normalized AUCs over 24 hours, every single patient demonstrated lower CyA-ME of the IS drugs allowed to negative clinical virus symptoms and PCR test in all of the exposure on t.i.d. than on b.i.d. dosing with an average relative bioavailability that was patients without any rejection (follow up from 1 to 5 years) and lymphoma. The drug 37.9% lower on t.i.d. than on b.i.d. dosing. The median dose-normalized AUC024h dosage was continuously adapted to the level of PCR test and today 4 patients remain free dropped from 1620 ng x h x kg/mL x mg (range 1253 to 4319) on b.i.d. to 1016 ng x h x of anticalcineurin, and 1 of them had only low dose of steroid, 8 continue triple therapy kg/mL x mg (range 712 to 1485, p= 0.0156, Wilcoxon’s matched pairs test) on t.i.d. dosing. with half dosage of AZA or MMF and low level of anticalcineurin trough level in sera Our results indicate t.i.d. dosing of CyA-ME results in significantly lower exposure when ( CsA 60 to 70 ng/ml, FK 3 to 5 mg/l). the same total dose is administered in two divided doses. This reduced exposure may increase the risk for rejection. Conclusion: Routinely virus detection is mandatory in tranplantation. A virus EBV or B K virus blood PCR positive test is a sign of over IS and allows to decrease the IS regimen with no risk of rejection and to cure the viral disease and avoid EBV B lymphoma that we had previously experienced.

COD. PP 243 COD. PP 244 TRIPLE IMMUNOSUPPRESSION WITH TACROLIMUS in Factors affecting growth in the first year following renal PEDIATRIC RENAL TRANSPLANTATION transplantation (Tx) A Duzova, FT Aki, A Bakkaloglu, N Besbas, R Topaloglu, F Ozaltin, M Bakkaloglu M Mallik, A R Watson, P Pugh, J Hayes Hacettepe University Faculty of Medicine , Hacettepe Univ. Faculty of Medicine, Dept. of Children & Young People`s Kidney Unit , Nottingham University Hospitals - City Hospital Pediatrics, Pediatric Nephrology and Rheumatology Unit , 06100 Ankara , Turkey CampusHucknall Road , NG5 1PB Nottingham NG5 1PB , UK UK

Aim: To assess the effect of tacrolimus in pediatric renal transplantation. Methods: Medical Background and Methods: records of 17 renal transplantation recipients (9 male, 8 female) receiving tacrolimus, were There is now increasing focus on growth with the advent of steroid avoidance. We reviewed examined. Acute rejection episodes, glomerular filtration rate (GFR) and side effects were the records of 115 children transplanted between 1988 and 2005 in whom growth had been evaluated. Results: The mean recipient age was 14.44 ± 3.42 years (range: 7-21). Six of the measured for at least one year post-Tx. Patients with syndromes, chromosomal grafts came from cadaveric donors, and 11 from living related donors. Fifteen patients abnormalities and cystinosis were excluded. None received growth hormone. Cyclosporin received basiliximab on day-0 and 4; and they were placed on immunosuppression with or tacrolimus combined with prednisolone and azathioprine were used in 97% of patients. prednisolone-azathioprine-tacrolimus (PAFk group, 8 patients), prednisolone- 91% received alternate day steroids by 6 months (mean dose 9mg/m2). mycophenolate mofetil-tacrolimus (PMFk group, 9 patients). The mean follow up time was 48 months (24-72). There were 2 AR episodes in PMFk group, at 5th and 12th month Results respectively, and no AR episodes in PAFk group. Mean GFR at the end of the 1st, 2nd, 3r d The mean age at time of Tx was 10.5yrs. 40/115 (35%) were transplanted pre-emptively and and 5th year were 92.7 ± 24.1, 116.9 ± 42.2, 94.2 ± 31.8, 74.3 ± 10.3 mL/min/1.73m2 23/115 (20%) received an LRD Tx. Mean height z score at Tx was –1.72 (SD ± 1.3). The respectively. There was no graft loss. Hypertension, hyperlipidemia and hyperglycemi a mean change in z score (Ä z) for the whole group between 0 and 6 months was 0.11 (95%CI were present in 10 (58.8%), 3 (17.6%), and 3 (17.6%) patients respectively; without 0.04-0.18; p<0.005) and 0.22 (95%CI 0.017-0.26; p<0.005) between 6 and 12 months. ? z gingival hyperplasia and hypertrichosis. Hyperglycemia resolved following tapering of scores in children 5-<10yrs(n=29) were significant between both 0-6mths and 6-12mths but prednisolone in 2 patients, and resulted in diabetes in the third one (5.9%). Conclusion: Ou r only significant between 6-12 months for those 0-5rs (n=19) and 10-<15yrs (n=45). The age single center experience supports that the outcomes with tacrolimus, steroid, and of Tx and gastrostomy feeding pre-Tx were significantly related to Ä z scores 0-12 months azathioprine or mycophenolate mofetil combination in pediatric renal transplantation are in a linear regression model. encouraging. Hyperglycemia was the main side effect. Conclusions The differences in linear growth rates at different ages between 0-6 months and 6-12 months post-Tx has implications for interpretation of trials using steroid-minimisation regimes if height at 6 months only is taken as an end-point. Children fed by gastrostomy pre-Tx grow less well in the first 6 months post-Tx and nutritional supplementation may need to be maintained for longer in this group.

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COD. PP 245 COD. PP 246 PLASMA BRAIN NATRIURETIC PEPTID AND CARDIAC FIFTEEN YEAR EXPERIENCE WITH PEDIATRIC KIDNEY FUNCTIONS IN PEDIATRIC DIALYSIS AND TRANSPLANT TRANSPLANTATION FOR FSGS: A SINGLE CENTER PATIENTS EXPERIENCE E Melek*, E Baskin*, N Cengiz*, Y Uslu*, K Tokel**, B Varan**, B Unal***, H S Mahesh, MD1, D Feuerstein, RN, NP1, M DelRio, MD1, S Greenstein, MD2, R Karakayali****, M Haberal **** Depts of Pediatric Nephrology*, Cardiology**, Schechner, MD2, K Freeman, DrPH1, F Kaskel, MD, PhD1 and V Tellis, MD2. 1Pediatric Biochemistry***, Transplant Surgery****, Baskent University, Ankara, Adana, TURKEY Nephrology, Children’s Hospital at Montefiore 2Transplant Surgery, 111 East 210th St., Baskent University hospital , Dept of Ped Nephrology 6.cadde 72/3 , 06490 Ankara , Bronx, NY, United States. Presenting author: S Mahesh Turkey Montefiore Medical Center (Ped Nephrology) , 111E 210th street , 10467 Bronx , NY USA

Cardiovascular complications are the most important causes of mortality and morbidity in Recurrence of focal glomerulosclerosis (FSGS) in pediatric renal transplantation (Tx) children with end stage renal disease and renal transplantation recipients. Brain natriuretic patients (pts) is reported as 30-50%. We present our 15-year experience of 37 pts with peptide (BNP) is a member of the family of natriuretic peptides. BNP is a cardiac FSGS who underwent renal Tx between 1990 and 2005. Mean age at first Tx was 21yrs (SD neurohormone specifically secreted by the cardiac ventricles in response to volume 6 yrs); 49% were African American (AA), 8% Hispanic, & 38% white. 54% were cadaveric expansion, pressure overload, and resultant increased wall tension. It is an important (CAD) Tx and 46% live donor (LD) Tx. Recurrence was defined as proteinuria >1 gm/day biological marker of left ventricular dysfunction. The aim of the study was to investigate and/or FSGS on biopsy. 14% of patients received pretransplant plasmapheresis (PP). BNP changes and the diagnostic value of BNP for cardiac functions in dialysis patients and Recurrent FSGS occurred in 46% of all Tx pts, all of whom received PP with 60% renal transplant recipients. remission. P values represent Chi-square statistics. Plasma BNP concentration was measured in 22 dialysis patients and 14 renal transplant recipients (median age:189.5 (77-264) months). Echocardiographic examinations were T ABLE performed to determine the relationship between BNP and cardiac functions. The median 1 & 5 yr graft survival were 84% & 67%, respectively (median graft survival 6.6 yrs). plasma BNP levels were significantly higher in dialysis patients than renal transplan t Despite recurrence, FSGS pts can achieve sustained graft function. With informed consent, recipients (106.25 pg/ml (6.52-2372), and 20.75 pg/ml (5-55.4 pg/ml) pg/ml respectively), transplantation is appropriate for FSGS. (P<0.001). Mean ejection fraction (EF), shortening fraction (SF), were significantly lower in dialysis group. There was significant negative correlation between plasma BNP levels and EFand SF (r¼ -0.68, r¼-0.622, respectively, p<0.01) and a positive correlation with left vetricular systolic diameter (p<0.01). In conclusion, plasma BNP levels are significantly higher in dialysis patients than those in renal transplant recipient, and high plasma BNP level is significantly correlated with dilated left ventricle and poor cardiac function. Renal transplantation has beneficial effects on cardiac functions and BNP value would be useful as a predictive marker of ventricular dysfunction in early identification of high risk patients.

COD. PP 247 COD. PP 248 Is Better Renal Survival Rate at Long Term Prognosis in Children with Catastrophic antiphospholipid syndrome in a 7-year-old girl Henoch-Schoenlein Nephritis? Jee Min Park, Jae Il Shin, Youn Ho Shin, Dong Soo Kim, Jae Seung Lee, Myung Joon Kim, Mir S, Yavascan O, Mutlubas F, Yeniay BS, Sonmez F Seung Koo Lee,Do Yun Lee , 560-70, won-dong , 447-060 Osan, Gyeonggi , South Korea Izmir Tepecik Teaching Hospital Department of Pediatric Nephrology , Izmir Tepeci k Teaching Hospital Department of Pediatric Nephrology , 35100 Izmir , Turkey Antiphospholipid syndrome (APS) has been recognized as the leading cause of vascular Henoch Schoenlein Purpura (HSP) is the most common vasculitis in childhood. The long- thrombosis in children. Less than 1% of patients with APS present with a life-threatening term prognosis is variable and depends on renal involvement. The aim of this study was to condition resulting from thrombosis in multiple organs and subsequent multi-organ failure, evaluate both clinical features of the children with HSP and the prognoses of short and long which is defined as catastrophic APS. A 7-year-old Korean girl presented with a drowsy term outcome of patients diagnosed as HSP nephritis (HSN). mentality and acute renal failure to our hospital. Blood urea nitrogen and serum creatinine This is a retrospective data study of all children with HSP hospitalized from January 1991 were 112 mg/dL and 5.1 mg/dL. Brain MRI showed high signal intensity in left occipital to December 2005. The patients with HSN were classified according to their initial area, suggesting cerebral infarction. Prothrombin time and activated partial thromboplastine presentation, histologic findings, type of treatment and clinical outcome. While 8 patients time were 15 second and 44 second. Lupus anticoagulant and anticardiolipine antibody Ig G with isolated mild proteinuria± hematuria, all patients with nephritic, nephrotic and both came out positive, which prompted us to the diagnosis of primary antiphospholipid syndrome required kidney biopsy. All patients have been evaluated through physical syndrome. The patient was treated in the intensive care unit until the hospital day 7 after examination and routine biochemical parameters once a two mounts. admission. Blood urea nitrogen and serum creatinine were gradually decreased without The patient population consisted of 141 children included 78 boys (55.3%) and 63 girls dialysis and urine output was favorable. MRI of the abdomen showed low signal intensity at (44.7%).ranging in age at disease onset from 2 to 17 years. The mean age was 8.9 ± 3.29 the lower pole of the right kidney, suggesting renal cortical infraction. On hospital day 14, years. The majority of our patients (82 children, 58.1%) had urinary abnormalities of she complained of severe pain in right inguinal area, which prompted us to perform a varying degrees. The clinical presentation, short and long term prognostic findings of the femoral venography. On venography, thrombosis of right external iliac vein was observed children with HSN are shown in Table 1. Hematuria±proteinuria was found as a good and we performed thrombectomy using 6 French thrombectomy catheter. Therefore, prognostic predictor (p<0.05). The full recovery from HSN determined to 54.8% after six continuous heparin months, 76.8% after a long term course. infusion was done on hospital day 14 through 19, and then changed to warfarin. She has Overall prognosis of HSN is good and long-term morbidity is predominantly associated been followed up at outpatient clinic for 3 years after diagnosis, with the maintenance of with initial presentation and renal involvement. No long term renal impairment occurred warfarin therapy without recurrent thrombotic attack. after normal urinalysis.

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COD. PP 249 COD. PP 250 Favorable outcome after renal transplantation in a 12 year-old girl with The effect of paraoxonase 1 (PON1) gene polymorphisms on the clinic anti-factor H (FH) autoantibodies-associated atypical hemolytic uremic course and renal involvement in the patients with Henoch-Schonlein syndrome (aHUS) Purpura T Kwon1, MA Macher1, V Baudouin1, A Maisin1, V Fremeaux-Bacchi2, MA Dragon- A Yilmaz, S Emre, B Agachan, I Bilge, H Yilmaz, A Ergen, T Isbir, A Sirin Durey2, C Loirat1 presenting author: T Kwon 1 Service de Néphrologie Pédiatrique, , Bahcesehir Funda mh. 07-04Blok D:49 , 34850 Istanbul , Turkey Hôpital Robert Debré. 2 Service d’immunologie Biologique, Hôpital Européen Georges Pompidou - Assistance publique- Hôpitaux de Paris, Paris, France It has been reported that oxidative stress and lipid peroxidation may play a role in the Service de Nephrologie Pédiatrique, Hopital Robert Debré , Hopital Robert Debré, Service pathogenesis of HSP. PON1, an antioxidant enzyme, reduces the susceptibility of LDL to de Nephrologie Pédiatrique, 48 boulevard Serurier , 75935 cedex 19 PARIS , France lipid peroxidation. The aim of this study is to investigate the effect of PON1 gene polymorphisms on the course, prognosis and renal involvement of HSP. We recently reported the presence of anti-FH autoantibodies in three children with aHUS Fifty six patients (30 male, 26 female) with HSP were compared with 53 healthy children in (Dragon-Durey MA, JASN 2005). We now report the post-tranplant course of one of them. respect to serum PON1 activity, PON1 Q/R192 ve PON1 L/M55 polymorphisms. This 10 year-old girl had aHUS which lead to end-stage renal failure within 2 months. PON1 Q/R192 genotype distribution was 58.6% QQ, 32.6% QR, 8.8% RR in HSP group; Complement assays showed consumption through the alternative pathway. FH antigenic 14.3% QQ, 50% QR, 35.7% RR in the control group. The frequency of QQ genotype was level and gene analysis were normal while FH activity was decreased (10%) due to anti-FH higher in the HSP group than in the control group and the presence of QQ genotype autoantibodies (2323AU/ml). Low C3 and high anti-FH IgG (850AU/ml) levels persisted increased the risk for developing HSP by 3.42-fold. after 18 months on dialysis. Anti-FH IgG level was unchanged (1000AU/ml) after three PON1 L/M55 genotype distribution was 50% LL, 43.5% LM, 6.5% MM in the HSP group; months of prednisone and azathioprine treatment, while it became undetectable after a 48% LL, 26% LM, 26% MM in the control group. The frequency of MM genotype was series of plasma exchanges (PEX) with fresh frozen plasma (6 sessions over 15 days). Anti- lower in the HSP group than in the control group and the presence of MM genotype FH IgG reincreased to 700 AU/ml one month after PEX cessation, but went down again to decreased the risk for developing HSP by 7.38-fold. low levels (200AU/ml) after a new course of 7 PEX. Rituximab (375 mg/m2 per week for 4 Serum PON1 activity was found to be higher in HSP group than in the control group. PON1 weeks) appeared to maintain this low level during the next 4 months. At this time, the child activity and distribution of PON1 Q/R192 and L/M55 genotypes were not different in the received a cadaveric donor renal graft. A PEX program was therefore established for 4 patients with nephritis compared to the patients without nephritis in the HSP group. months, starting just before the transplantation procedure, daily during the first week, and In conclusion, our results suggest that PON1 activity and PON1 polymorphisms may play a then gradually tapered off. The immunosuppressive regimen included basiliximab, role in the pathogenesis of HSP. But there is no significant relationship between PON1 prednisone, cyclosporine and mycophenolate mofetil. During the one year of follow up, no activity or PON1 polymorphisms and risk for developing nephritis. HUS recurrence has occured, creatinin level remained normal, and anti-FH IgG barely detectable. We propose that intensive PEX therapy should be considered for children with anti-FH autoantibodies-associated aHUS, as early as possible.

COD. PP 251 COD. PP 252 From allograft rejection to generalized thrombotic microangiopathy – ROLE OF MESANGIAL FIBRINOGEN DEPOSITION IN THE Contribution of acquired inhibitors of ADAMTS 13 activity PATHOGENESIS OF CRESCENTIC HENOCH-SCHOENLEIN A Charpentier, B Mougenot, V Fremaux-Bacchi, G Deschênes, A Veyradier, Albert NEPHRITIS IN CHILDREN Bensman, T Ulinski JI Shin, JM Park, JH Kim, JS Lee, PK Kim, HJ Jeong Department of Pediatrics, Yeoncheon Hôpital Trousseau , Department of Pediatric Nephrology , 75012 Paris , France County Hospital, Kyunggi, Korea Department of Pediatrics, Pathology, and the Institute of Kidney Disease, Yonsei University College of Medicine, Seoul, Korea Thrombotic microangiopathy (TMA) is a well described complication in solid organ Yeoncheon County Hospital , Department of Pediatrics, Jeon Gok-Eup, Eundae-Ri , 577-36 transplantation and mostly associated with anticalcineurin medication. Vascular rejection Yeoncheon-Goon , Kyunggi-Do South Korea and cytomegalovirus infection have been reported as contributing factors A nine-year old renal transplant recipient with an uneventful post transplant follow up of Background: To clarify the role of mesangial fibrinogen deposition in crescentic Henoch- four years was admitted for elevated serum creatinine level. Non-compliance to Schoenlein nephritis (HSN). immunosuppressive treatment was suspected. The kidney biopsy revealed acute interstitial Methods: A retrospective analysis of 21 children with HSN treated with and vascular rejection including lesions suggestive for TMA. He received immunosuppressants. Serial renal biopsies were performed before and after treatment. They methylprednisolone pulses followed by a normalisation of serum creatinine. Three more were divided into two groups according to the immunofluorescent course of fibrinogen acute rejection episodes - all steroid responsive - occurred, and baseline serum creatinine deposition: group I (n = 9), no or decreased deposition; group II (n = 12), persistent or remained satisfactory. Two months later the boy presented with severe abdominal pain, increased deposition. concomitant with elevated serum creatinine. After two weeks he presented rapidly Results: There were no differences between the two groups in renal manifestations or progressive life threatening symptoms including asthenia, bilateral pyramidal syndrome, laboratory and histological findings at presentation. However, the activity index afte r haemoptysis, and abdominal pain. Serum haptoglobin levels became undetectable at this immunosuppressive treatment was significantly decreased in group I (mean, 7.9 (SEM, 0.7) time and platelet count was 70,000/mcl, suggesting TMA to be responsible for the v 2.9 (0.4); p = 0.008) and unchanged in group II (mean, 6.8 (SEM, 0.3) v 6.0 (2.1)). The generalized symptoms. Cerebral MRI revealed generalized ischemic white matter lesions. chronicity index was unchanged in group I, but increased in group II (mean, 0.8 (SEM, 0.3) ADAMTS13 activity was <5%, while factor H, I, B, and CD46 were normal. Daily plasma v 1.8 (0.3); p = 0.02). Univariate analysis revealed that the only factor significantly related exchanges against fresh frozen plasma resulted in immediate improvement of all symptoms. to persistent or increased fibrinogen deposition was age more than 9 years (p = 0.03). All attempts to discontinue PE were unsuccessful and transplantectomy resulted in Furthermore, the intensity of fibrinogen deposition at the second biopsy correlated normalization of generalized symptoms, hemolysis, and ADAMTS13 activity (110%). positively with the age at onset (R2= 0.306; p = 0.009) and changes in the percentage of Multiorgan involvement has never been reported in acquired ADAMTS13 deficiency post crescents (post-treatment crescents (%) minus pretreatment crescents (%)) correlated transplant. Rapid regression of all systemic symptoms after transplantectomy may suggest positively with the intensity of fibrinogen deposition at the second biopsy (R2= 0.193; p = that renal TMA was responsible for acquired ADAMTS13 deficiency and generalization o f 0.046). TMA lesions. Conclusions: This study indicates that fibrinogen deposition has an important role to play in renal injury of crescentic HSN and reflects persistent severe histological activity.

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COD. PP 253 COD. PP 254 ACUTE RENAL FAILURE IN A PATIENT WITH TAKAYASU Trafficking of shiga toxin/shiga-like toxin-1 in human glomerular ARTERITIS micr ovascular endothelial cells and human mesangial cells ZB Özcakar, F Yalç ›nkaya, B Altas, N Çakar, N Kara, N Uncu, H Ergün, S Fitöz, S Yüksel, M Warnier1, J Geelen1, W Roemer2, L Lesieur2, M Amessou2, L van den Heuvel1, L T Sancak, M Ekim Monnens1, L Johannes2. 1. Radboud University Medical Centre, Nijmegen 2. Institut Ankara University School of Medicine , Department of Pediatric Nephrology , 06100 Curie, Paris Presenting author: B. van den Heuvel Ankara , Turkey Radboud University Medical Centre , Dept Pediatric Nephrology , 6500 HB Nijmegen , The Netherlands The Netherlands Takayasu arteritis (TA) is a chronic, idiopathic, inflammatory disease that affects the aort a and its major branches and it is rarely seen in children. A 14 year old girl was admitted to a The objective of this study was to determine the intracellular transport route of Shiga-like local hospital 7 months ago with the complaints of high fever, weakness, weight loss and (SLTx) and the highly related Shiga toxin (STx) in human glomerular microvascular respiratory distress. She had been found to have elevated blood pressure and the diagnosis endothelial cells (GMVEC) and human mesangial cells with or without preincubation with of TA had been established. She was sent to our hospital for autotransplantation. Physical TNF-alpha. Establishing the transport route, unknown before this study, will provide a examination revealed decreased pulses in the right upper extremity and bruit over the better understanding of the cytotoxic effect of SLTx. subclavian arteries. MR angiography showed increased wall thickness in the distal We used the non-toxic receptor-binding B-subunit (STxB), which is identical between abdominal aorta, complete obstruction in the right renal artery (RA) and severe obstruction SLTx1 and STx. The transport route of STxB in human GMVEC and human mesangiale in the left RA. Percutaneous transluminal angioplasty (PTA) was planned for the left RA cells was studied by immunofluorescence microscopy and biochemical assays that allow the occlusion. During the procedure dissection of the left RA occured therefore a stent was quantitative analysis of retrograde transport from the plasma membrane to the Golgi placed. One week later severe left flank pain and vomiting started, progressive oliguria and apparatus and the endoplasmic reticulum (ER). anuria had developed. Renal function tests detoriorated rapidly and serum creatinine level In both cell types, STxB was detergent resistant membrane associated and followed the reached 4.7 mg/dl. 24 hours after the onset of symptoms angiography was carried out for retrograde route. When compared to HeLa cells, retrograde transporter was less efficient, the treatment of a suspected thrombus. Thrombectomy and balloon dilatation was however. TNF-alpha upregulated Bb3 expression by five or two-fold in human GMVEC or performed. Heparin infusion was started after the procedure and the patient was followed on mesangial cells, respectively, without affecting the efficiency of STxB transport to the ER. hemodialysis. A total of 11 hemodialysis sessions were performed. Renal function tests In conclusion, our study shows that in human CMVEC and mesangial cells, STxB follows improved in the following days and the patient was withdrawn from hemodialysis. This the retrograde route to the Golgi apparatus and the ER, albeit less efficiently than in HeLa case was presented in order to draw attention to the role of PTA and stent implantation in cells. TNF-alpha treatment increases the amount of cell associated STxB , but not the treatment of TA especially in patients with a single functional kidney. After the retrograde transport as such, making it likely that the strong TNF-alpha –induced procedure these patients should be followed with great caution due to the probable sensitization of mesangial cells and GMVEC for the toxic action of SLTx is not due to a complications such as thrombus formation and acute renal failure. effect on the intracellular trafficking of the toxin.

COD. PP 255 COD. PP 256 Sjögren`s syndrome as a cause of end-stage renal failure in childhood Methylenetetrahydrofolate Reductase (MTHFR) Polymorphism and S A Johnson S A Hulton, Birmingham Children`s Hospital M A Brundler, Birmingham Homocysteine levels in Juvenile Lupus Nephritis (JLN) Children`s Hospital A Huisson, Birmingham Heartlands Hospital C M Taylor, Birmingham M C Ribeiro 1, R Vaz 1, A Leitão 1, P Pinto 2, I Brito 2, C Afonso 1, H Jardim 1 1 Children`s Hospital Pediatric Department, 2 Rheumatology Department, S. João Hospital, Porto, Portugal Birmingham Children`s Hospital , Department of Nephrology , B4 6NH Birmingham , UK , Rua António Patricio 104 R/C esq , 4460-204 Sra da Matosinhos , Portugal

We describe 2 adolescents who presented with end-stage renal failure and features of Hyperhomocysteinemia (Hcy) and MTHFR gene polymorphisms define a well-known Sjögren’s syndrome (SS). prothrombotic state. Coagulation and fibrinolytic abnormalities may play an important role in glomerular damage. Case 1 We examine the relationship between plasma Hcy and MTHFR gene polymorphisms in A 13-year-old girl presented with end-stage renal failure. Investigations revealed atrophic JLN. kidneys, lymphopenia, thrombocytopenia, hypergammaglobulinaemia (IgG 32.9g/l), anti- Plasma Hcy and MTHFR polymorphisms were determined in 18 children with JLN. nuclear antibodies (ANA) >1:1600, anti-SS-A antibody 88 IU/l and anti-SS-B 23 IU/l Medical records were reviewed retrospectively including renal histology, according to the (normally both <10 IU/l). Double stranded DNA antibodies (dsDNA) were undetectable. WHO classification. Immunological, serum and urinary biochemical data at the time of Renal biopsy showed severe, chronic damage with glomerular sclerosis, marked tubular nephritis onset and remission were obtained. atrophy and chronic lymphocytic interstitial infiltration. There was no clinical evidence of JLN patients presented homocysteinemia levels within the normal range (<15 mmol/l) and the sicca complex. Schirmer’s test and salivary gland biopsy were normal. there were no correlations between homocysteinemia and immunological, serum and urinary biochemical variables. There were no significant differences in NN, NM and MM Case 2 genotypes and N and M allelic prevalence between JLN patients and controls. There was no A 14-year-old boy with hereditary angio-oedema due to complement C1 esterase inhibito r association between WHO JLN class and MTHFR genotypes or alleles. There was no (C1INH) deficiency, presented with end-stage renal failure. Investigations revealed positive difference in biochemical data observed at onset or remission between genotypes. ANA (>1600IU/l), hypergammaglobulinaemia (IgG 22.4g/l), anti-SS-A >100 IU/l and anti- Remission serum creatinine level was significantly lower in the M allele. The presence of N SS-B 11.1 IU/l. Plasma C4 and C1INH were consistently low. dsDNA antibodies were allele was associated with higher titles of globular sedimentation rate, at the time of undetectable. Renal biopsy showed extensive glomerular sclerosis, crescent formation and nephritis onset, and antinuclear antibodies at remission. The N allele was associated with mesangial matrix expansion, with marked interstitial inflammation and fibrosis. A history o f higher serum albumin and proteins, at nephritis onset. dry eyes was given. Schirmer’s test was positive. In conclusion, despite its limitations, our results support the hypothesis that the N allele of MTHFR may be associated with higher JLN activity both at onset and remission. The M End-stage renal failure in childhood has not been previously attributed to SS. This may be allele seams to be a favourable predictive factor for renal function recovery in this because clinical manifestations of SS differ from those in adults - sicca syndrome may be population. absent or delayed and non-specific symptoms such as fever, malaise and arthralgia may occur. Disease may present with extraglandular involvement. Hypergammaglobulinaemia, anti-SS-A or SS-B antibodies, high ANA titres and rheumatoid factor can occur early and support the diagnosis. We propose that SS be considered in the differential diagnosis o f renal failure in children.

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COD. PP 257 COD. PP 258 Antineutrophil cytoplasmic antibody-associated glomerulonephritis in CYCLOSPORINE A induction and maintenance therapy of LUPUS type I diabetes mellitus NEPHRITIS K Vondrak, Z Sumnik, E Simkova, J Dusek, T Seeman, J Kreisinger, P Dvorak, J Stejskal JHH Ehrich*, O Szakal, J Gellerman Children’s Hospital, Hannover Medical School, Carl and J Janda Neuberg Str. 1, 30625 Hannover, Germany University Hospital Motol , Dept. of Pediatrics, V Úvalu 84 , 150 06 Prague , Czech Medical Scool of Hannover , Carl-Neuberg-Strasse 1 , D-30625 Hannover , Germany Republic BACKGROUND: Treatment of children with lupus nephritis (LN) is a challenge because of Antineutrophil cytoplasmic antibody (ANCA) glomerulonephritis (GN) is a very rare the clinical and histological heterogeneity of renal involvement. We analysed the effect o f disease in childhood. The association of ANCA GN and type I diabetes and chronic Cyclosporine A (CSA) for inducing and maintaining remission in children with different lymphocytic thyroiditis as well has been described until now only in one child. types of LN. Case report: A girl aged 14 years has been treated for 6 years for type I diabetes with goo d METHODS: In our retrospective non-randomized study we analysed the efficacy of CSA compensation. First symptoms of vasculitis (butterfly rash, slight ANA positivity) appeared induction and maintenance treatment in 24 caucasian children (18 F, 6M) with a mean age 1.5 year before diagnosis. Further inflammatory symptoms – fever, polyarthritis, high ESR of 11.0 years at onset of LN. together with hematuria, nephrotic proteinuria (PU) (2.3g/day), significant myeloperoxidase RESULTS: After a mean follow-up of 8.1 years, 20 out of 24 (83%) patients were in (MPO)-ANCA and proteinase 3 (PR3)- ANCA positivity resulted in renal biopsy. Ligh t complete remission (11/13 with NoS at onset of LN, 0/2 with NiS, 7/7 with HU + PU, 2/2 microscopy and immunofluorescence proved focal pauci-immune GN without changes with PU). Five out of 6 patients with a histological lesion of WHO type II were in complete typical for diabetic nephropathy. Crescents were present in 21/46 glomeruli. Serum remission, 3/4 with type III, 6/8 with type IV and 6/6 with type V GN. Three of 24 children creatinine, BUN and blood pressure (BP) were normal. Pulses of methyl-prednisolone (MP) had entered complete remission, however, they developed chronic renal failure with a GFR and cyclophosphamide followed by CyA revealed only temporary effect - PU decreased to between 57 and 76 ml/min/m2 after 2 or 3 relapses. One of 24 children did not enter 0.16g/day within five months, ESR, PR3-ANCA and MPO-ANCA decreased and clinical remission and had persistent PU. The relapse rate of patients on maintenance therapy was symptoms disappeared. As expected, the patient required very high doses of insulin during 9/23 (39%) children. the MP treatment. Subsequently, the vasculitis relapsed (polyarthritis, high ESR, PR3- CONCLUSION: The combined PRED plus CSA induction treatment had a positive effect ANCA and MPO-ANCA high titer again). Switch to mycophenolate mofetil did not bring on children with LN and severe proteinuria irrespectively of the underlying histological any improvement, repeated pulses of MP had only a transient clinical effect. Despite lesions, even if patients had been unresponsive to previous immunosuppressive regimen unfavourable clinical course, renal function and BP remain normal (PU < 0.5g/day) such as CYC. We conclude that CSA may play a substantial role in the treatment of patients Conclusion: this case report shows the association of MPO- and PR3-ANCA GN with with LN and gross proteinuria. diabetes mellitus and other autoimmunity. This association has not been described up to date.

Supported by the grant MSMT 0021620819

COD. PP 259 COD. PP 260 RENAL INVOLVEMENT IN CHILDHOOD VASCULITIS CARDIOLOGIC DISORDERS DURING NONSPECIFIC N Çakar, F Yalç ›nkaya, Z B Özçakar, D Soy, Y Uçar, S Fitöz, N Uncu, N Kara, M Ekim VASCULITIS IN PERITONEALLY DIALYSED CHILD – A CASE Ankara University School of Medicine , Department of Pediatric Nephrology , 06100 REPORT Ankara , Turkey M Miklaszewska 1, K Zachwieja 1, D Droýdý 1, J A Pietrzyk 1, J Rubik 2, B Chodór 3 1 Dialysis Unit, University Children`s Hospital of Cracow, Poland 2 Nephrology Clinic, The The aim of the study is to evaluate the characteristics of renal involvement in childhood Children’s Memorial Health Institute 3 Silesian Center for Heart Disease vasculitis. The demographic, clinical and laboratory features of patients with systemic Dialysis Unit, University Children`s Hospital of Cracow , Wielicka 265 , 30 - 663 Kraków , vasculitides in two institutions between 1994 and 2006 were reviewed. A total of 814 Poland patients (Henoch Schönlein purpura: 778, polyarteritis nodosa: 30, Takayasu arteritis :5 and Wegener’s granulomatosis: 1) were enrolled. Renal involvement was seen in 134 patients A 10 – year old girl in a poor general condition, with ureamic symptoms, manifestations of (17.2%) with HSP, 13 patients (43%) with PAN, 2 patients with TA (40%) and in WG pulmonary oedema, without any previous signs and symptoms of renal diseases was patient. Hematuria was present in 130 (97%) HSP patients. One-hundred and twenty admitted in 2001 to University Children`s Hospital. An automated peritoneal dialysis patients had proteinuria (89.5%) and 50% of them were in nephrotic range. Acute nephritic (APD) was initiated. In order to explain the causes of CRF a comprehensive diagnostics presentation was detected in 17 (13%), nephrotic syndrome in 9 (6.7%) and renal failure in was carried out. The laboratory studies revealed ANCA (++), ANA (1+), the 5 (3.7%) patients. Renal biopsy was performed in 44 cases; these were classified as grade I histolopathology revealed cirrhotic kidneys, cystoureterography – was normal. As in (18.2%), grade II (%36.3)), grade III (31.9%), grade IV (6.8%), grade V (4.5%) and grade echocardiography a congestive cardiomiopathy signs were noted - a metildigoxin treatment VI (2.3%) according to ISKDC. Thirteen of 30 patients with PAN had renal involvement. was initaited. During APD treatment girl had pericarditis sicca (once) and pleuropneumonia Hematuria was observed in 9 (69%) and proteinuria in 7 (54%) patients. Angiography (twice). Having introduced oral methylprednisolone – partial improvement of patient’s revealed aneurysims in 8 patients. Renal biopsy was performed in 4 cases; 3 of them had general condition was achieved. During reducing methylprednisolone dosage – tenderness focal segmental crescentic glomerulonephritis and one of them had necrotizing vasculitis. of small joints, difficult and painful swallowing, ulcerations of oral mucous membrane, Renal arteries were affected in 2 of 5 TA patients. Both of these patients had hypertension. necrotic skin lesions and another pleuropneumonia appeared. Suspecting vasculitis – Unilateral nephrectomy was performed in one patient before admission and the other patient intravenous methylprednisolone pulses and series of plasmapheresis (PF) were introduced. already had a single functional kidney. The sole patient with the diagnosis of WG was After the 3rd PF – a ventricular fibrillation occurred – the patient had to be defibrillated 17 presented with renal failure. Renal involvement constitutes an important part of childhood times. The main cause of this complication might have been high metildigoxin level (3.19 vasculitides. Collaboration with pediatric nephrologists is necessary to increase the ng/ml), which during PFs paradoxically increased despite previous reduction of its dose. scientific base of investigation on the diagnosis and treatment especially regarding renal Having achieved the stabilization of patient’s condition – methylprednisolone pulses were outcome. kept on and afterwards mycophenolate mofetil and carvedilol therapy was introduced – reaching significant improvement of patient’s condition and function of cardiovascular system. Heart biopsy carried out in 2006 revealed depletion of cardiomyocytes and no vasculitis features. At present a chance of combined heart and kidney transplantation as a definitive therapy form is being considered. Pediatr Nephrol (2006) 21:1493–1635 1587

COD. PP 261 COD. PP 262 TAKAYASU ARTERITIS IN TURKISH CHILDREN Massive thrombosis in a 14-year-old boy with Wegener`s

N Çakar, F Yalç ›nkaya, A Düzova, S Çal›þkan, A Þirin, E Bask›n, K Bek, A Soylu, A granulomatosis Bayaz›t, Z Bircan, S Özen, N Uncu, M Ekim On behalf of Turkish Pediatric Hypertension I Zaluska-Lesniewska (presenting author), A Zurowska, P Czarniak, M Drozynska-Duklas, Study Group Z Gockowska Ministry of Health D ›þkap› Children`s Hospital , Department Of Pediatric Nephrology , Medical University of Gdansk , Department Paediatric Nephrology , 80-211 Gdansk , 06110 Ankara , Turke y Poland

In order to investigate the clinical characteristics and outcomes of Takayasu`s arteritis (TA) The WeCLOT Study (WG Clinical Occurrence of Thrombosis) has drawn attention to the using standardized criteria for diagnosis, disease activity, and angiographic classification 15 high incidence of venous thrombotic events in adults with Wegener’s granulomatosis (WG). children with Takayasu’s arteritis were evaluated retrospectively. Mean follow-up period o f We present one of the first reports of severe thrombotic complications accompanying this 29.50 ± 24.86 months (range 2-84, median 28 months). There were 11 girls and 4 boys. The type of rare vasculitis in childhood. mean age at diagnosis was 12.53±2.80 (range 8-17, median 12) years. The most common WG was diagnosed in a 14-year-old boy who presented with recurrent sinusitis, otitis complaints on admission were headache (80%), abdominal pain (33%), fever (27%) and media, mastoiditis, erythrocyturia and slight range proteinuria ( 0,42 g/24 h) and had weight loss (13 %). One patient presented with visual loss. Physical examination on elevated anti-proteinase 3 (anti PR3) antibodies (148,2 U/ml, normal < 5 U/ml). Intravenous admission revealed hypertension (73%), absent pulses (60%), and bruits (33%). The methylprednisolone treatment (1,0 g/day) was given for 3 days followed by oral Mantoux test was strongly positive in 2 patients and 1 of them had active renal tuberculous prednisolone (80 mg/day) and cyclophosphamide (2 mg/kg/day). Simultaneously with the disease. start of therapy, he developed a painful swollen left leg. Doppler ultrasound revealed deep Angiography revealed type I in 10 of the pts (aortic arch,descending thoracic and abdominal and superficial venous thrombosis of both the lower extremities. In spite of anticoagulation aorta), type II in 4 pts ( descending thoracic aorta and abdominal aorta) and type IV in 1 therapy, a week later he developed pulmonary thromboembolism and pleuritis. Due to the patients (abdominal and pulmonary artery). The most commonly involved vessels were the progression of disease, plasmapheresis was started (22,7 ml/kg x 7 exchanges). He carotis communis (53%), renal (53%) and subclavian arteries (46%). All patients received responded to the treatment with resolution of symptoms and decrease of anti PR3 antibodies corticosteroid therapy and further immunosupressive therapy were added in 12 patients to normal values. (cyclophosphamide in 8 cases, methotrexate in 8 cases, azathioprine in 5 cases and Laboratory investigations did not reveal any known acquired risk factor for infliximab in 1 case). Angioplasty was performed in 5 patients, aorto-renal by-pass in 2, hypercoagulability. aortic graft in 1, and placement of renal arterious stent in 1. In 9 patients whom followed up Conclusion to 24 months or more, although laboratory markers of inflammation showed remission, Wegener’s granulomatosis in children can be accompanied by severe thrombotic control angiography revealed progression of lesions in 4 patients, remained unchanged in 2, complications. and partially healed in 3. One patient died with pulmonary hemorrhage due to pulmonary arteries involvement.

COD. PP 263 COD. PP 264 Serum IGF-1 and IGFBP-3 Levels in Henoch Shonlein Purpura STRUCTURE OF THE RENAL TUBULES DYSFUNCTION IN Yildiz B, Kural N, Aydin B, Caglar F, Colak O CHILDREN WITH PRELITHIASIS Eskisehir Osmangazi University, Department of Pediatric Nephrology , Meselik , 26480 V N Luchaninova*, O V Semeshina, V V Popova, A N Nee Eskisehir , Turkey Vladivostok State Medical University , 2, Ostryakova prospekt , 690002 Vladivostok , Russia Henoch-Schonlein Purpura (HSP) a common systemic vasculitis of childhood, may affect the skin, joints, gastrointestinal tract, and the kidney. The role of growth factors in HSP The term Prelithiasis (PL) signifies a group diseases that include disturbances of unclear. In this study, we were wanted to investigat role of insulin like growth hormone metabolism (Hyperoxaluria, Hyperuraturia). These impairments result in changes of kidney (IGF-1) and insuline like growth hormone-3 (IGFBP-3) in HSP. A 18 patiens in whom HSP function at different components of the nephron. was diagnosed and 18 healthy children were included in the study. Serum IGF-1, IGFBP-3, Objective: To study structure attendant tubules disturbances of kidneys in children with complement C3 and C4, immunoglobulins (Ig), erythrocyte sedimentation rate (ESR), Prelithiasis. leucocyte counts, C-reactive proteine (CRP) and protein/creatinin ratio in urine were Renal tubules dysfunction in 334 children with Prelithiasis and 146 healthy persons were measured. Also, urine analysis and stool occult blood (SOB) examination were performed. investigated. Metabolic disturbances were found in the form of Hyperoxaluria in 114 Hematuri were found in 8 (44,4%) patients but except one patient, heavy proteinuria were children, as Hyperuraturia in 94, and both Hyperoxaluria and Hyperuraturia were revealed not found. Ten (55,6%) patients had positive SOB. Serum IGF-1 and IGFBP-3 levels were in 126 children from group with PL. Urinalysis included determination of ammonia significantly higher in patients than in the control subjects (170,2±32,5/107,7±17,8 ng/ml excretion, titrying acids, uric acid, oxalates, H+ ion concentration, Na+, Cl-, K+, Mg++, and 3,9±0,3/2,2±0,2 ng/ml; p<0,01, respectively). Serum IGF-1 and IGFBP-3 levels were Ca++, and P+. significantly higher in HSP with hematuria than without hematuria and control subjects Results: Excretion of urine acid was 2,5 times more than the control group, and oxaluria (253,2±56,6/117,3±31,7/107,7±17,8 ng/ml, p=0,008 and 4,4±0,6/3,5±0,4/2,2±0,2 ng/ml, was 4,4 times higher (p<0,001). The concentration ratio of Na+/ Cl- was two times less than p<0,05, respectively). Serum IGF-1 levels did not significantly differ in HSP with positive the control group (p<0,001). The concentration of Mg++ion was half that of the control SOB than without SOB. But serum IGFBP-3 levels were significantly higher in HSP with group and the excretion was 1,7 times less. The concentration of Ca++ ion was 2,1 times positive SOB than control subjects (3,4±0,5/2,2±0,1 ng/ml, p<0,05 respectively). Serum more than the control group (p<0,001) and the excretion was 1,3 times higher (p<0,001). IGFBP-3 levels were negative correlated with serum IgG levels (r= -487, p=0,047). The Ca++/ Mg++ ratio was 4,5 times more than the control group (p<0,001). Finding of Conclussion: The increased IGF-1 and IGFBP-3 in HSP probably reflects the reactive ammonioacidogenesis were no different from those in the control group. The concentration growth processes in affected tissue and especially high serum IGFBP-3 levels may be show and excretion of the P+ ion and the K+ ion were normal. the activity of HSP. Conclusion: Dysfunction of the renal tubules associated with Prelithiasis contribute to increasing excretion Ca++, Cl-; decreasing excretion of Na+, Mg++ and impairment Na+/ Cl- and Ca++/ Mg++ ratio.

1588 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 265 COD. PP 266 Intestinal oxalate absorption in children with idiopathic calcium A new therapy for Nephrolitiasis in pediatric population urolithiasis measured with the standardized [13C2]oxalate absorption T Papalia, R Greco, R Bonofiglio test Department of Nephrology , Ospedale Annunziata , 87100 Cosenza , Italy Italy 1Przemysùaw Sikora, 2Gerd E. von Unruh, 3Albrecht Hesse, 1Maùgorzata Zajàczkowska, 4Bernd Hoppe 1. Department of Pediatric Nephrology, Medical University of Lublin, Phillantus niruri (Pn) is a plant belonging to the Euphorbiaceae family. It’s used in Brazilian Poland 2. Department of Internal Medicine I, University of Bonn, Germany 3. Department folk medicine by patients (pts) affected by urolithiasis. of Urology, University of Bonn, Germany 4.Division of Pediatric Nephrology, University Previous reports showed that an infusion of Pn to pts with renal calculi was effective in Children’s Hospital Cologne, Germany promoting stone elimination. DSK , Department of Pediatric Nephrology, Chodzki 2 , 20-093 Lublin , Poland In this work we estimate the effect of Pn intake in 6 children with kidney stones. We evaluated the effect of administration of Pn (Uristone 2 g/die) in 6 children (4 M/ 2 F, 9 Increased intestinal oxalate absorption may lead to urolithiasis resulting from secondary ± 5 years old) affected by urolithiasis. The Pn has been administered for 3 months in 4 hyperoxaluria. This problem has been rarely the subject of investigations before the children wih CaOx urinary stones and for 6 months in 2 with struvite stones. Nobody of introduction of the [13C2]oxalate absorption test. This relatively simple and non-invasive them had been undergone Extracorporeal shock wave lithotripsy. test gave rise to numerous studies on intestinal oxalate absorption. They demonstrated that Urinary and blood electrolytes were determined at baseline, 1 month and at the end of the up to one-third of adult patients with calcium oxalate urolithiasis were oxalate study. The patients were studied by renal ultrasonography at baseline, 1, 3, 6 months. hyperabsorbers. Such studies have not yet been performed in children. Therefore, the There were no differences in the mean values of urinary and plasma parameters before and purpose of our study was to evaluate intestinal absorption patterns of oxalate in children. after Pn intake, except for a significant reduction in the mean urinary calcium in 4 The study comprised 63 children with calcium urolithiasis aged 4.3-18.5 years. The controls hypercalciuric pts (6±1,3 vs 3,5±1 mg/Kg/die). were 30 healthy children aged 5.7-16.8 years. Under standardized conditions, the disodium In this follow up we observed that stone diameter was smaller than baseline renal ultrasound salt of [13C2]oxalic acid was administered orally at the dose of 25 mg for patients with < 30 control. The efficacy of Pn was more evident in children affected by struvite stones. kg body weight or 50 mg with a body weight of > 30 kg, respectively. In children with This work suggests Pn may represent an alternative form of treatment and/or prevention of urolithiasis, the mean oxalate absorption was significantly higher than that in controls urolithiasis, interfering with the early stages of stone formation. (15.63 ± 8.80 % vs 11.42 % ± 6.24 %). Based on the results obtained in controls, an Pn may represent a non toxic, low-cost and bioavailable therapeutic alternative for the intestinal oxalate absorption > 15 % was assumed abnormal. According to this criterion, management of urolithiasis in the children. oxalate hyperabsorption was diagnosed in 49.3 % of patients. In addition, we found a statistically significant correlation between intestinal oxalate absorption and urinary oxalate excretion (r = 0.542, p<0.001). Conclusion: Intestinal hyperabsorption of oxalate is an important risk factor for hyperoxaluria and hence for the development of calcium oxalate urolithiasis. Further studies are needed to explain the mechanism(s) of increased intestinal oxalate absorption.

COD. PP 267 COD. PP 268 PEDIATRIC UROLITHIASIS: 8 YEARS EXPERIENCE OF SINGLE EFECTIVENESS OF TREATMENT WITH BISPHOSPHONATES IN CENTER CHILDHOOD OSTEOPOROSIS Dursun I,Poyrazoglu HM,Dusunsel R,Gunduz Z,Gurgoze MK,Demirci D,Kucukayd›n M E Barrios, M J Hernández González, M D Rodrigo Jiménez*, S Armas Suarez, F Claverie- , Erciyes University Medical Faculty, Departments of Pediatric Nephrology , 38200 Martin, V García Nieto Pediatric Nephrology Unit, Hospital Universitario Nuestra Señora Kayseri , Turkey de Candelaria, Tenerife. *Hospital Son Dureta, Palma de Mallorca, Spain Hospital UniversitarionNuestra Señora de Candelaria , Pediatric Nephrology Unit , 38010 Purpose: The aim of this retrospective study is to investigate the clinical features, metabolic Santa Cruz de Tenerife , Spain and anatomic risk factors for kidney stones formation in our patients group. Materials and Methods: Between 1998 and 2005, 179 children (94 females, 85 males) Introduction referred to our department because of urolithiasis were enrolled to study. All patients were Bisphosphonates are synthetic analogues of pyrophosphate that inhibit bone resorption by investigated with respect to clinical presentation, urinary tract infection, anatomic their action on osteoclasts. They have been used in adults and have been found to be abnormalities, stone localization, positive family history, analysis of stone composition, effective and well tolerated in osteoporosis treatment. urinary metabolic risk factors (hypercalciuria, hyperuricosuria, hypocitraturia, Material and methods hyperoxaluria, hypomagnezuria), treatment modality and prognosis. We present the bone mineral density of 23 patients (21 males, 2 females) 13,3±4,18 years Results: The mean age at diagnosis of stone disease was 4.54.1 years. The mean follow- old (r: 2,3-17,3) with secondary osteoporosis before and after treatment with up duration was 8 (range, 1-98) months. The major clinical presentations of our patients bisphosphonates ( 17 alendronate, 2 pamidronate and 4 zoledronic acid), during a time of were abdominal pain in 64 children (35.8 %), hematuria in 25 (14%), flank pain in 22 (12.3 2±1,2 years (r:0,45-5). Osteocalcin, PTHi, 25OHD3, 1,25(OH)2,D3, FATR, levels were %), urinary tract infection in 19 (10.6 %), micturition difficulty in 14 (7.8 %) and dropping determined as well as the deoxypyridinolines/creatinine quotient in the second urine. Bone stone in 8 (4.5 %). Urinary tract infection was detected in 20 % of patients on admission. mineral density was measured before and after treatment with a Hologic QDR 4500 system. Forty three children (24%) had a urinary tract abnormality. A family history of stone We analysed data with no parametric test of Wilcoxon. disease was recorded for 98 patients (54.7 %). Stones were located within renal parenchyma Results in 90 patients. Hypercalciuria was determined in 55 of 130 children (42.3 %), In all cases ZDMO improved: ZDMO before treatment was -3,15±0,54 (r: -4,04 -2,15), hyperuricosuria in 40 of 73 children (54.8 %), hyperoxaluria in 26 of 95 children (27.4 %), ZDMO after treatment was -2,12±0,97 (r: -3,64 0,47) (p: ,001). DMO significantly hypocitraturia in 26 of 95 children ( 27.4 %) and hypomagnezuria in 17 of 33 children (51.5 increased after treatment; 0,7176±0,15 vs. 0,5653±0,13 (p:0,000). Dpyr/cr quotient %). In 63 of 91 children who had stone analysis, calcium oxalate was major mineral. significantly decreased after treatment; 21,21±15,38 vs. 43,54±38,04 (p: 0,004). Only one Surgical treatment was performed in 50 children, ESWL in 41 children. We follow up patient showed a bone fissure after treatment. In five cases, we found minor side effects: currently 119 children. Renal stone persisted in 40 of them. one patient had fiver, one had symptomatic hypophosphatemia with bone and muscular pane, one had asymptomatic hypocalcaemia and hypophosphatemia, one showed digestive intolerance, and one had nocturnal enuresis. Conclusions Bisphosphonates reduces fractures and significantly increases DMO in osteoporotic pediatric patients. Markers of bone resorption decrease after treatment, reflecting a decreased in bone turnover. Some patients had minor side effects

Pediatr Nephrol (2006) 21:1493–1635 1589

COD. PP 269 COD. PP 270 Thiazides effect over bone mineral density in hypercalciuric children Bone mineral density and response to furosemide stimuli in children M Monge, M González-García, M I. Luis Yanes, F Henriquez-Palop, A Ibáñez-Alonso, V with idiopathic hypercalciuria García-Nieto Pediatric Nephrology Unit, Hospital Universitario Nuestra Señora de M D Rodrigo Jiménez*, M I Luis Yanes, M J Hernández González, M Monge Zamorano, E Candelaria, Tenerife, Canary Islands, Spain Barrios,V García Nieto Pediatric Nephrology Unit, Hospital Universitario Nuestra Señora Hospital Universitario Nuestra Señora de Candelaria , Pediatric Nephrology Unit , 38010 de Candelaria, Tenerife. *Hospital Son Dureta, Palma de Mallorca, Spain Santa Cruz de Tenerife , Spain Hospital Universitario Nuestra Señora de Candelaria , Pediatric Nephrology Unit , 38010 Santa Cruz de Tenerife , Spain Thiazides are used in hypercalciuric (IH) children due to their hypocalciuric effect and subsequently for the possible increment in bone mineral density (BMD). We studied BMD Bone mineral density (BMD) is reduced in approximately 40% of children with idiopathic in IH children in order to determine the effect of thiazides on rates of bone mineral gaining. hypercalciuria (IH). Blood monocytes isolated from IH patients tend to produced Patients and methods. Twenty three children (13 males and 10 females) with IH were significantly more cytokines that would increase osteoclastic activity, and produce a treated with thiazides. 20 of them took clortalidone (dose: 25 mgr/day). The other three took reduction in BMD. Nevertheless, an acidification defect would also contribute to the hydroclorothiazide (dose: 25 mg/day). At the beginning of the study the mean age was reduction of BMD. 11,13±2.39 years (range 6.6-14.4 years). At the end of the study the age was 13.75±2.69 Patients and Methods. We have studied 60 children (25M, 35F) affected of IH, with an age years (range 7.5-19.2 years). BMD was performed using a Hologic QDR 4500 SL of 10.2±3.2 years (range: 3-18). Bone mineral densitometry (Hologic QDR 4500 SL densitometer (DEXA). The results were expressed as absolute values and as Z-score of densitometer; DEXA) and an acidification test (1 mg/kg of oral furosemide) were carried BMD (Z-BMD) and as Z-score of body mass index (Z-BMI). out in all children. We considered acidification defect when the minimum pH was above Results. At the end of treatment, the patients had higher BMD and BMI but differences 5.35, and osteopenia when Z-BMD was smaller than -1. were not statistical significant when both parameters were expressed as Z-score. Plasma Results. Children that did not acidify with furosemide stimuli (Group A, n=13; 21.7%) had creatinine and calcium levels were significantly incremented and calciuria and citraturia values in the urinary elimination of titratable acidity (TA) more reduced than those that did levels were significantly reduced. acidify (Group B) (8.2±4.8 vs. 18.1±10.3 µEq/min/1.73 m2, p=0.003), although differences 11 out of 23 children improved Z-BMD after the treatment but they presented significantly in the ammonium elimination (NH4+) were not observed. Group A children had Z-BMD higher BMI at the end of the study when compared to the non improved children. There values reduced compared to those of Group B (-1.07±0.87 vs. -1.62±0.77, p=0.04). A direct were no statistically differences between both subgroups with regard to the sex, the relationship between TA and BMD (r= 0,3; p=0.02) and between TA and calcitriol levels biochemical parameters or the thiazide doses. (r= 0.41, p=0.03) was observed. Conclusions. We have observed that the improvement in BMD in some hypercalciuric Conclusions. The acidification defect after furosemide stimuli is a marker of BMD children is not due to thiazides but to increasing BMI. reduction risk in children with IH. It is difficult to establish the causal relationship between both parameters, although a partial acidification defect could increase the bone resorption.

COD. PP 271 COD. PP 272 URINARY SODIUM/POTASSIUM EXCRETIONS AND THEIR AGE-RELATED DIFFERENCES IN URINARY CALCIUM RELEVANCE WITH URINARY CALCIUM EXCRETION IN EXCRETION OF HEALTHY TURKISH SCHOOLCHILDREN TURKISH SCHOOLCHILDREN A Gür Güven, M Koyun, S Akman, S Filiz, H Akbas, Y E Baysal, M G ültekin, N Dedeoglu M Koyun, A Gür Güven, S Akman, S Filiz, H Akbas, Y E Baysal, M G ültekin, N Dedeoglu , Akdeniz University, Medical Faculty, Department of Pediatric Nephrology , 07070 , Akdeniz University, Medical Faculty, Division of Pediatric Nephrology , 07070 Antalya , antalya , Turkey Turkey Generally accepted limit to define hypercalciuria is an urinary calcium/creatinine ratio of The main therapeutic approach in children with hypercalciuria is to limit sodium intake and (UCa/Cr) Q 0.21, and has been created in a study performed 3 decades ago in a restricted increase potassium intake. The objective of this study was to assess the relationship number of children. We aimed to investigate age-related distrubution of UCa/Cr in school- between urinary sodium and potassium excretions with calcium excretion. aged children from southern Turkey. This cross-sectional study was performed in Antalya, southern Turkey. Non-fasting, secon d Non-fasting, second morning urine samples were collected from 2143 children, who were morning urine samples were collected from 2143 children, who were selected by systemic randomly selected from 14 schools between November 2004 and March 2005. The 95th randomization method from 14 schools located in different parts of the city between percentile value was used for the upper limit of UCa/Cr ratio for each age group. A total o f November 2004 and March 2005. Urinary sodium and potassium were measured by ion 2143 children, 1161 boys (54.2%) and 982 girls, aged 7-14 years, were included in the selective analysis, calcium by Hitachi kit and creatinine by kinetic Jaffe method. Children study. 25, 50, 75, 90th and 95th percentile values of UCa/Cr ratio for each age were with a urinary calcium/creatinine ratio (UCa/Cr) Q 0.21 were considered as hypercalciuric. calculated and shown in the table. For statistical analysis, student T test and Pearson correlation test were used. Mean UCa/Cr of children aged 7-12 years was significantly higher than that of children A total of 2143 children, 1161 boys (54.2%) and 982 girls, aged 6-14 years (mean 10.25 ± aged 13-14 years (0.11±0.10 vs 0.07± 0.06, p<0.05). 2.36 years), were included in the study. Mean urinary sodium/potassium ratios (UNa/K) and We found that 90th percentile (not 95th) of UCa/Cr of children aged 8-12 years were close mean urinary sodium/creatinine ratios (UNa/Cr) of hypercalciuric children were higher than to 0.21, generally accepted limit for hypercalciuria, only matched with the 95th percentile of that of children without hypercalciuria (3.78±1.97 vs 2.43±1.29, p<0.05 and 3.05±1.42 vs 13-14 year olds. This may cause overestimation in the diagnosis of hypercalciuria in 1.98±1.41, p<0.05, respectively). No statistical significance was found in urinary younger children at least in our country. We suggest that age-specific reference values fo r potassium/creatinine ratios (UK/Cr) between children with and without hypercalciuria UCa/Cr should be re-established in each population. (0.91±0.43 vs 0.86±0.42, p>0.05). Moreover, UNa/K and UNa/Cr ratios were correlated with UCa/Cr ratios (r=0.41, p<0.01 and r=0.35, p<0.01, respectively); but UK/Cr was no t (r=0.05, p>0.01). Our results show that urinary potassium excretion is not as prominent as sodium excretion in children with hypercalciuria. It seems that, as a therapeutic approach, sodium restriction is more important than potassium supplementation in this entity. 1590 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 273 COD. PP 274 LOW FREQUENCY OF PAIN A TTACKS IN CHILDREN WITH PROTEIN INTAKE IN CHILDREN WITH IDIOPATHIC RECURRENT ABDOMINAL PAINS ( RAPs ) AND HYPERCALCIURIA (HC) AND/OR HYPERURICOSURIA (HU) C Polito, C Santoro, M Rea, V Narciso, F Iaccarino, L Graziano, A La Manna, , G Lama NEPHROLITHIASIS C Polito, L Graziano, N Valentini, L Pintozzi, L Tafuro, A La Manna, R Bismuto R Del Dipartimento di Pediatria, Nefrologia Pediatrica Seconda Università degli Studi di Napoli , Gado, , G Lama Via L. De Crecchio, 4 , 80138 Naples , Italy Italy Dipartimento di Pediatria, Nefrologia Pediatrica Seconda Università degli Studi di Napoli , Via L. De Crecchio, 4 , 80138 Naples , Italy Italy We evaluated the daily urinary excretion of urea (Uurea) – which closely reflects protein intake – in four age and sex- matched groups of children: 1) HC, 2) HU, 3) HC+HU, 4)

More than 100 different conditions have been associated with RAPs in children, although in controls. Each group included the 56 subjects required for 80% power, with type 1 error of most cases no organic disease was found despite extensive investigation. Abdominal 0.05 and type 2 error of 0.20, to detect a difference of 15% in Uurea among the 4 groups. ultrasound (US) has a generally low diagnostic value in RAPs. To determine clinical All were on free diet and were taking no drugs. Uurea was significantly (Confidence Interval excluding 0) higher in HC, HU and HC+HU hallmarks of urinary apparatus involvement may improve the cost-effectiveness of the investigations in children with RAPs. than in controls. HC+HU had Uurea significantly higher than HC and HU but UCa similar We evaluated the frequency of pain attacks in 44 consecutive children with RAPs , who to HC and UUA similar to HU. HC and HU had similar Uurea. UCa was significantly (r = were diagnosed by us having renal calculi ( 4-20 mm in diameter ) at renal US. 23 of them 0.46) correlated with Uurea in HC only; UUA was significantly (r = 0.46) correlated with were referred under the diagnosis of RAPs and 21 under the diagnosis of hematuria and/or Uurea in HU only. No correlation between Uurea and UCa or UUA resulted in HC+HU dysuria associated with RAPs. although they had the highest Uurea. 23/44 (52%) had no history of dysuria or gross hematuria. 16 out of the 23 had normal Evenly high protein intakes may be associated with HC or with HU in different subjects. An urinalysis at our first visit and were investigated for nephrolithiasis just because of RAPs even higher protein intake is associated with HC+HU without an evenly higher UCa than and a family history of urinary stone disease. The frequency of pain attacks in our patients HC nor an evenly higher UUA than HU. These data indicate a different individual (mean 2.7 3.6 SD, median 1.2 days/month) was over 4-fold lower than that reported in (genetic?) sensitivity among HC, HU and HC+HU children to their excessive dietary children with gastrointestinal (GI) organic or functional RAPs. 40/44 (90%) of our pts had protein intake 4 days of pain per month which is considered an index of healing in children with functional GI RAPs. The low frequency of pain attacks is a strong distinctive feature of RAPs associated with nephrolithiasis. Renal US is recommended in children with RAPs and family history of nephrolithiasis having 4 or less pain attacks per month although hematuria and dysuria are lacking

COD. PP 275 COD. PP 276 METABOLÝC EXAMINATION AND CLINICAL PRESENTATION Ceftriaxone associated nephrolithiasis OF PEDIATRIC UROLITHIASIS IN ISTANBUL : A SINGLE M Mohkam*1, A Gharib 2, S Armin 3, H Daneshmand 4, M Sharifian 1 1. Pediatric CENTER STUDY Nephrologist,Shahid Beheshti university,Tehran-IRAN 2. Pediatric Pathologist,Shahid Gökçe Ý, Alpay H, Özen A, B›y›kl› N, Özdemir N Marmara University Medical Faculty, Beheshti university,Tehran-IRAN 3. Pediatric Infectious diseases,Shahid Beheshti Pediatric Nephrology Department university,Tehran-IRAN 4. Pediatrician, Shahid Beheshti university, Tehran-IRAN Marmara University Medical Faculty , Marmara University Medical Faculty Pediatric Shahid Beheshti University, Mofid Children’s Hospital , Pediatric Nephrology Department, Nephrology Department Tophanelioðlu Cad. No 13-17 Altunizade , 81190 Ýstanbul , Shariati Ave , 1546815514 Tehran , IRAN Iran Turkey The prevalence of urolithiasis is 1.7 - 4.1% in female and about 4 - 9% in male worldwide. To evaluate clinical findings and metabolic examination of 76 children with urinary tract N owadays one of the most important etiologic factors for stone formation is the use of calculi followed by pediatric nephrology outpatient clinic during 1998-2006. various medications. Ceftriaxone is a widely used third-generation cephalosporin. It is The study evaluated the age at diagnosis, sex, presenting symptoms, family history, the generally considered very safe, but complications such as biliary pseudolithiasis, and rarely, localizations, dimensions and numbers of stones, urinary metabolic examinations, physical, nephrolithiasis have been reported in children. The aim of this study was evaluation of laboratory, and radiologic findings. prevalence of nephrolithiasis fallowing ceftriaxone therapy in children. This is a Quasi There were 35 boys (46%) and 41 girls (54%) with their ages at diagnosis ranged from 1 Exprimental and also a before and after study conducted between Oct. 2003 – Dec. 2005 on all children admitted due to pyelonephritis in Mofid Children’s Hospital. All patients were months-16 years with an average of 5,3 years in girls and 3 months to 15 years with an average of 6,3 years in boys respectively. At the time of diagnosis 24 (31,6%) children were treated with 75 mg/kg Ceftriaxone as intravenous infusion method. The first renal younger than 1 year of age. UTI’s were present in 54,2% of children younger than 1 years. ultrasonography was performed at 1st – 2nd day of admission and was repeated at the last The most common presenting symptom was hematuria in 22 patients (%28,9) followed by day of admission. We also evaluated target patients for the third time with renal abdominal pain in 18 patients (23,7%). For the 75,5% of the 49 patients urinary metabolic ultrasonography three months after treatment. After detection of stones in ultrasonography, examination was not normal (Tabe 1). The most common metabolic abnormality was blood and timed urine samples were obtained for hematologic and biochemical tests to rule hypercalciuria (39%) which was followed by hypocitraturia (31%). The 89,3 % of stones out other causes of nephrolithiasis. We evaluated 284 pediatric patients, 65% were female were located in kidneys, 3,1% were located in bladder and 7,7% in ureters. Positive family and 35% were male. The first ultrasonography was normal in all of our patients. On the history of urolithiasis was reported in 52,2% of patients. Stones measuring 6 mm and larger second evaluation the presence of stones were reported in four children (1.4%). An 8 year were associated with abnormal ultrasonographic findings mainly hydronephrosis, none o f old girl and a 4 month old, 2 and 3 year old boys, biochemical laboratory tests and random the stones measuring 3 mm or smaller (microlithiasis) resulted in ultrasonographic findings. urine for stone evaluation were in normal ranges. Last kidney ultrasonography was The presenting symptoms of urolithiasis show a wide spectrum so that high index of performed 3 months after discontinuation of treatment, the results were normal in four suspicion is important for early detection. Metabolic abnormality was found in 75% of the patients. Ceftriaxone can cause nephrolithiasis. This complication can be self limited as far cases. The detection of small stones and determination of the nature of stones may provide as hydration and mobilization are maintained. us appropriate management that would prevent subsequent renal injuries and recurrrences. We also emphasize the importance of screening for UTI’s in patients with urolithiasis especially those under 1 year of age.

Pediatr Nephrol (2006) 21:1493–1635 1591

COD. PP 277 COD. PP 278 THE INDUCTION OF SODIUM DEPENDENT HYPERTENSION IS GORDON SYNDROME: A FAMILY WITH THREE AFFECTED RELATED TO UP-REGULATION OF SODIUM AND CHLORIDE MEMBERS TRANSPORT PROTEINS EXPRESSED ALONG THE THICK A Bettinelli° N Borsa °°and M G Bianchetti* Department of Pediatrics, °Mandic Hospital, ASCENDING LIMB OF HENLE’S LOOP (LOH) Merate (Lecco), Italy and * Mendrisio and Bellinzona Hospitals, Switzerland; °°Laboratory G Capasso of Molecular Biology, IRCSS Policlinico, Milan (Italy). Chair of Nephrology Department of Pediatrics Second University of Napoli , Policlinico Department of Pediatrics , Mandic Hospital , 23807 Merate , Lecco Italy Nuovo Pad. 17 Via Pansini 5 , 80131 Napoli , Italy Background It has been demonstrated that hypertension of the Milan rats (MHS) is sodium-dependent. Gordon syndrome (Online Mendelian Inheritance in Man #145260) is a rare, genetically Recently we have found (Am J Physiol 2005) that the induction of hypertension in this heterogeneous familial disorder presenting with hyperkalemia, metabolic acidosis and strain of animals is related to increased sodium chloride transport along the LOH. In the tendency towards severe arterial hypertension. A hitherto unreported Italian family with present study we explore the molecular mechanism(s) related to this event by quantifying three affected members is described. the mRNA (real time PCR) and the protein (immunoblotting) abundance of sodium and Report chloride transporters expressed in the LOH cells. To this end, MHS rats were studied at 23- A 16-year-old girl (Case 1) with history of headache presented with hemiparesis on the left 25 days after birth, i.e. before the onset of overt hypertension. Milan normotensive (MNS) side and severe arterial hypertension (185 /110 mm Hg). The diagnostic work-up disclosed rats of the same age were used as controls. The following proteins were studied : alfa1- hyperkalemia (6.9 mmol/L), hyperchloremia (112 mmol/L) and hypobicarbonatemia (11.0 subunit Na+-K+-ATPasi; Na+-K+-2Cl- co-transport (NKCC2); K+ channel (ROMK); mmol/L). Treatment with hydrochlorothiazide was successful (initial dosage 37.5 mg/day; chloride channels (ClCKa and ClCKb); chloride channel sub-unit (Barttin). At mRNA level current dosage 12.5 mg/day). Growth was normal. these proteins were significantly increased in MHS as compared to MNS animals : 216% Blood pressure, plasma sodium, potassium, chloride and bicarbonate were normal at birth in for alfa1-subunit Na+-K+-ATPasi; 137% for NKCC2; 79% for ROMK; 162% for ClCKa; two female dizygous twins (Cases 2 and 3), the daughters of Case 1. However, 54% for ClCKb and 117% for Barttin. These results were fully confirmed by the hyperkalemia (6.9 respectively 6.4 mmol/L), hyperchloremia (110 respectively 111 immunoblotting experiments: indeed alfa1-subunit Na-K-ATPasi increased by 52%; mmol/L), metabolic acidosis (pH 7.183 respectively 7.181; plasma bicarbonate 12.5 NKCC2 by 36%; ROMK by 96% and ClCKa-b by 70%. These data demonstrate the respectively 12.0 mmol/L) in the presence of normal blood pressure and growth were noted enhanced coupled activities of luminal ROMK channels and NKCC2 co-transporter at the age of 14 months. In both infants the values normalized soon on hydrochlorothiazide together with the stimulation of the basal lateral Na+-K+ pump and ClCKa-b plus Barttin 12.5 mg/day. drive active and passive sodium chloride reabsorption in this portion of the nephron, thus Conclusions contributing to the development of hypertension. The present experience with three patients affected by Gordon syndrome indicates that clinically relevant hypertension-related target organ damage may develop before adulthood and confirms that the disorder is mostly transmitted in an autosomal dominant fashion. Furthermore the experience indicates that hyperkalemia and hyperchloremic metabolic acidosis sometimes present during infancy (on the contrary arterial hypertension tends to develop later in life). Finally treatment with thiazides is a very satisfactory long-term management.

COD. PP 279 COD. PP 280 PPAR -ã2 GENE PRO12 ALA MUTATION IN TURKISH CHILDREN Anemia after the angiotensin II receptor blocker irbesartan WITH METABOLIC SYNDROME Simonetti GD 1, Konrad M 1, Bianchetti MG 2, von Vigier R 1 1 Division of Paediatric B. S. Yeniay= presenting author F. Mutlubas A. Berdeli S. Mir Y. Tabel O. Yava þcan Nephrology, University Hospital, Inselspital Berne, Switzerland, 2 Department of Ege University Faculty of Medicine Pediatric Nephrology Department , Ege University pediatrics, Ospedale Mendrisio and Bellinzona, Switzerland Faculty of Medicine Pediatric Nephrology Department Bornova , 35100 Izmir , Turkey University children`s Hospital - Inselspital Berne , paediatric nephrology , 3010 Berne , Bern Switzerland BACKGROUND: Peroxisome proliferator-activated receptors (PPARs) are nuclea r hormone receptor superfamilies of ligand-activated transcription factors, and the PPAR-ã2 Case report subtype regulates adipocyte differentiation, lipid metabolism, and insulin sensitivity. Aim o f A 12 year old boy with history of congenital nephrotic syndrome of the Finnish type and a this study to investigate the distribution of PPAR-ã2 gene mutation in metabolic syndrome poor renal function (plasma creatinine approximately 210 µmol/l, urinary protein/creatinine patients. ratio 48 mg/mmol) 7 years after a cadaveric transplantation is on treatment with the METHODS: This study was performed on 22 patients (body mass index (BMI)>25kg/m2) immunosuppressants mycophenolate and sirolimus. This unusual immunosuppression was aged from 5 to 20 years (average: 12,43,7 years) . 22 healthy subjects with same ages started 2 years ago because of untreatable arterial hypertension and chronic allograft were included in as control group. Ambulatory blood pressure measurements, nephropathy while on therapy with cyclosporine A, azathioprin and prednisolone. In anthropometric measurements, fasting glucose-insulin, lipid profiles were measured in addition he is on antihypertensive medication with the calcium-channel blocker amlodipine obese children. Homeostatic model assessments(HOMA-IR) and quantitative insulin (0.08 mg/kg/d), with the b-blocker metoprolol (1.7 mg/kg/d) and with the angiotensin II sensitivity check indices(QUICKI) were calculated. Metabolic syndrome was diagnosed receptor blocker irbesartan (up to 10 mg/kg/d) started 3 years ago. Severe hypo-regenerative according to the NCEP-ATP III guidelines:1)waist circumference Q80cm 2) normocytic anemia (hemoglobin 70 g/l) was noted. Acute or chronic infection was ruled out (including Parvovirus B19), parenteral iron and treatment with erythropoietin failed to Q Q Q hypertriglyceridemia 150mg/dL 3)LDL cholesterol 50 mg/dL 4)hypertension increase hemoglobin, which rapidly increased within 4 weeks (hemoglobin 111 g/l) after 130/85mmHg 5)fasting hyperglycemiaQ110mg/dL. withdrawing irbesartan. PPAR-ã2 gene mutation was analyzed from genomic DNA by the PCR-RFLP base d Discussion method. This is the first pediatric case of anemia caused by medication with an angiotensin II RESULTS: All patients admitted with hyperten sion. Hyperlipidemia was present in 52.5% receptor blocker. The case brings out two points. First, anemia is a rare but recognized of subjects. 9% of patients had impaired glucose tolerance, 45.4% had insulin resistance and adverse event in patients with chronic kidney diseases on treatment with drugs blocking the 36.3% had hyperinsulinism. 20 children were found to have Pro12Pro wild type genotype, 2 renin-angiotensin II-aldosterone system such as converting enzyme inhibitors and had Pro12Ala heterozygote genotype in patients. Controls were all determined as Pro12Pro angiotensin II receptor blockers. Second, since recent reviews dealing with these drugs do genotype. Neither patients nor controls had been observed homozygote genotype for not sufficiently mention this relevant side effect, pediatric nephrologists are at risk to Ala12Ala polymorphisms (Table 1). There was no significant difference in BMI, wais t overlook their potential to induce anemia, therefore exposing affected children to circumference, blood pressure, lipid profiles, insulin levels, HOMA and QUICKI between unnecessary and often expensive diagnostic procedures. the two different PPAR-ã2 genotypes. CONCLUSION:The Pro12Ala mutation of the PPAR-ã2 gene may not be associated with metabolic syndrome in Turkish children. These results must be supported with large study populations.

1592 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 281 COD. PP 282 A case of low-renin hypertension associated with precocious puberty RENOVASCULAR HYPERTENSION IN CHILDHOOD: A NATION- Simonetti GD 1, Goeggel B 2, Diana A 2, Cachat F 3, Flück C 4, Janner M 4 1 Division of WIDE SURVEY Paediatric Nephrology, Department of Paediatrics, University Hospital, Inselspital Berne, A K Bayazit1, F Yalcinkaya2, N Cakar3, A Duzova4, Z Bircan5, S Aslan6, A Bakkaloglu4, Switzerland, 2 Department of Paediatrics, Neuchatel, Switzerland, 3 Division of Paediatric N Canpolat7, N Akkök 3, A Sirin8, M Ekim2, A Oner9, S Akman10, S Mir11, E Baskin12, Nephrology, CHUV Lausanne, Switzerland, 4 Division of Paediatric Endocrinology, H Ozpoyraz13, A Noyan1, I Akil14, S Bakkaloglu15 and A Soylu16. 1Pediatric Department of Paediatrics, University Hospital, Inselspital Berne, Switzerland. Nephrology, Cukurova University, School of Medicine, Adana, Turkey; 2Pediatric paediatric nephrology , University children`s Hospital - Inselspital Berne , 3010 Berne , Nephrology, Ankara University, School of Medicine, Ankara, Turkey; 3Pediatric Bern Switzerland Nephrology, SSK Diskapi Hospital, Ankara, Turkey; 4Pediatric Nephrology, Hacettepe University, School of Medicine, Ankara, Turkey; 5Pediatric Nephrology, Kocaeli Background University, School of Medicine, Izmit, Turkey; 6Pediatric Nephrology, Yuzuncu Yil Low renin hypertension is rare. Precocious puberty is usually idiopathic in girls, but may be University, School of Medicine, Van, Turkey; 7Pediatric Nephrology, Cerrahpasa observed in undiagnosed patients with congenital adrenal hyperplasia (CAH). We present a University, School of Medicine, Istanbul, Turkey; 8Pediatric Nephrology, Istanbul 5-year old girl with precocious puberty and low renin hypertension. University, School of Medicine, Istanbul, Turkey; 9Pediatric Nephrology, Dr. Sami Ulus Case Report Cocuk Hospital, Ankara, Turkey; 10Pediatric Nephrology, Akdeniz University, School of This African girl was diagnosed with idiopathic precocious puberty at the age of 2 years and Medicine, Antalya, Turkey; 11Pediatric Nephrology, Ege University, School of Medicine, blocked with the gonadotropin releasing hormone agonist triptorelin. At age of 5 years she Izmir, Turkey; 12Pediatric Nephrology, Baskent University, School of Medicine, Ankara, presented with arterial hypertension (157/82 mm Hg). Height was 126 cm (+ 3.7 SDS), T urkey; 13Pediatric Nephrology, Erciyes University, School of Medicine, Kayseri, Turkey; bone age 8 years. History was negative for familial arterial hypertension and licorice 14Pediatric Nephrology, Celal Bayar University, School of Medicine, Manisa, Turkey; ingestion. Creatininemia and urinalysis were normal. Mild hypokalemia (3.5 mmol/L) and 15Pediatric Nephrology, Gazi University, School of Medicine, Ankara, Turkey and severe hyporeninemia (1.3 ng/L; reference: 20-74) were noted. Plasma aldosterone (283 16Pediatric Nephrology, Dokuz Eylul University, School of Medicine, Izmir, Turkey. pmol/L; reference: 80-970), urine catecholamines, urine steroids profile and adrenal CUKUROVA UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF imaging (MRI) were normal. Glucocorticoid-remediable aldosteronism (GRA) was ruled PEDIATRIC NEPHROLOGY, 01330 ADANA , Turkey out by dexamethasone suppression test. Blood pressure and hypokalemia normalized INTRODUCTION AND AIMS: Renovascular disease accounts for 8-10% of all cases of (106/59 mm Hg) on amlodipine 0.35 mg/kg/d and amiloride 0.18 mg/kg/d. Arterial pediatric hypertension whereas in adults it s incidence is about 1%. Turkish Pediatric hypertension is not a known side effect of triptorelin. Hypertension Group aimed to constitute the first registry database for childhood Discussion renovascular hypertension in Turkey. Low renin hypertension with hypokalemia may be caused by apparent mineralocorticoid excess, GRA, primary aldosteronism, Cushing or Liddle syndromes and CAH. Although we METHODS: Demographic, clinical and laboratory data were recruited from Pediatric performed detailed studies, we were unable to identify the underlying cause of both arterial Nephrology centers. hypertension and precocious puberty. We therefore conclude that currently available diagnostic techniques sometimes fail to identify the cause of low renin hypertension. RESULTS: The registry was composed of 43 patients; 27 girls, 16 boys from 14 Pediatric Alternatively this case suggests the existence of a new, hitherto unreported cause of this Nephrology centers. The age at presentation ranged from 20 days to 17 years. Of these, 13 abnormality, potentially related to precocious puberty. (30 %) had fibromuscular dysplasia; 12 (28 %) Takayasu arteritis; 6 (14 %) neurofibromatosis; 1 (2 %) Williams syndrome; 1 (2 %) Kawasaki; 1 (2 %) midaortic syndrome; 1 (2 %) extrinsic compression to renal artery, 8 (19 %) unspecified bilateral renal artery stenosis. The mean blood pressure at the diagnosis was 167.1/109.9 mm Hg. Renovascular hypertension was found incidentally in 8 children, the others were symptomatic cases. Chief complaints were headache (20), seizure (8), epistaxis (2), growth retardation (2), cognitive dysfunction (2), and poliuria (1). Diagnosis was made with conventional angiography in 37 cases, MR angiography in 3 cases, CT angiography in 2 cases, and captopril DTPA scintigraphy in 1 case. Twenty-two children had bilateral, 21 children had unilateral renal artery stenosis. Treatment consisted of percutaneous transluminal angioplasty (17), surgery (aorta-renal bypass in 4, renal autotransplantation in 4), nephrectomy (4) or antihypertensive drugs only (14).

CONCLUSIONS: Fibromuscular dysplasia was the most common cause of renal artery COD. PP 283 stenosis followed by Takayasu arteritis. The importance of vasculitic disease, especially EVALUATION OF THE SAFETY OF SHORT ACTING NIFEDIPINE Takayasu arteritis should not be underestimated in children with renovascular hypertension. USE IN CHILDREN WITH SEVERE HYPERTENSION SECONDARY TO ACUTE POST STREPTOCOCCAL COD. PP 284 GLOMERULONEPHRITIS(APSGN) P Nourse, MI McCulloch TAKAYASU ARTERITIS IN CHILDREN: PRELIMINARY , PO Box 19063 7505 Tygerberg South Africa , 7505 Cape Town , Western Cape South EXPERIENCE WITH CYCLOPHOSPHAMIDE INDUCTION Africa FOLLOWED BY METHOTREXATE FOR MAINTENANCE TREATMENT Objectives of study: The objective of this study was to evaluate the safety of the use of short A Duzova, Y Bilginer, S Ozen, R Topaloglu, N Besbas, A Bakkaloglu acting nifedipine to treat severe hypertension secondary to APSGN in our paediatric Hacettepe University Faculty of Medicine , Hacettepe Univ. Faculty of Medicine, Dept. of population. Pediatrics, Pediatric Nephrology and Rheumatology Unit , 06100 Ankara , Turkey

Methods: We conducted a retrospective chart review of paediatric patients with acute pos t Background: Takayasu Arteritis (TA) is the vasculitis of aorta and its main branches. A streptococcal disease who received nifedipine for severe hypertension. We recorded the high relapse rate is observed in adults with various treatment protocols. dose per kilogram administered; all BP measurements and all adverse events reported Aim: We aimed to review our experience with cyclophosphamide (CYC) induction within six hours of a nifedipine dose regardless of the likelihood that those events were followed by methotrexate (MTX) for maintenance treatment in the last 7 years. related to the use of nifedipine Patients and Method: Six patients (4 F, 2 M; with an age range of 12-17 years) were diagnosed as TA according to the recently suggested criteria for childhood TA. Two were Patients: Patients admitted to hospital with the diagnosis of Acute Post Streptococcal siblings. Five had involvement of both the thoracic and abdominal aorta. Headache and Glomerulonephritis (APSGN) between 1999 and 2002 abdominal pain were the leading symptoms. One was erroneously diagnosed as Crohn’s . disease whereas in two the diagnosis was delayed since they were suspected to have familial Main outcome measures: Adverse events and BP recordings within six hours of the Mediterranean fever. Acute phase reactants were elevated in all except for the girl on administration of nifedipine. colchicine. One patient died due to pulmonary vasculitis at the first month of therapy. The remaining four with involvement of both the thoracic and abdominal aorta and branches Results: The charts of 129 patients with APSGN were found during that time and we received steroids with oral CYC (oral) for 12 weeks followed by weekly MTX for 12-18 reviewed 198 doses of nifedipine given to 57 patients. Mean age 7,4yrs (+/-3yrs); mean months. One patient who had vasculitis of the abdominal aorta and renal artery, received dose of nifedipine was 0,23mg/kg (+/-0,08mg/kg). One adverse event was noted 2hrs after a steroid + MTX. nifedipine dose. Results: All entered remission. Aortic bypasses were performed in two whereas aorta-renal Of the 44 doses where the BP was done within 2hrs 34% of patients had a MAP reduction bypass was performed in the other two patents. In one patient the contra-lateral renal artery of greater than 25%. Mean nifedipine doses were not significantly larger in those doses stenosis was managed by a balloon dilatation and unilateral nephrectomy had to be where there was a >25% reduction in MAP vs those where there was A<25% reduction in performed in another one. One had a relapse at one year with re-stenosis of the graft. There BP(p<0,05%). Nifedipine was effective in reducing BP in 78% of doses. were no side effects and all patients were fine at their last visits. Conclusion: The presented single-center experience suggests that CYC induction followed Conclusion: Short acting nifedipine can be used safely and is effective to treat children with by MTX is an effective and safe treatment for childhood TA. Large, multicenter studies are severe hypertension secondarily to APSGN. needed to confirm this observation. Pediatr Nephrol (2006) 21:1493–1635 1593

COD. PP 285 COD. PP 286 Prospective, single centre study of the efficacy of ramipril in the Abnormal urinary steroid profiles in hypertensive obese children treatment of obesity related hypertension in children. F Paize (presenting) & C Jones Cs Bereczki, A Barath, F Papp, S Turi , 107, Ellenbrook Road , M28 1ES Manchester , UK University of Szeged , Dept. Paediatrics, Koranyi str. 14-15 , H-6720 Szeged , Hungary BACKGROUND OBJECTIVE: The effect of overweight on blood pressure elevation (BP) is more frequently present in childhood. Several studies have demonstrated the efficacy of angiotensin- There is a recognised association between obesity and hypertension. The basis of this converting enzyme inhibitors (ACEI) therapy in obese hypertensive adults, but data on relationship is not completely understood. We have investigated abnormalities of adrenal children are very limited. androgen and cortisol metabolites in a series of hypertensive obese children. METHODS: 110 obese (BMI z score >2.5 SD) primary hypertensive (systolic or diastolic blood pressure 95th) children (aged 6 -17 years) were enrolled to this single centre CASE SERIES prospective study. Patients received ramipril (0.1-0,15 mg/bwkg/day) once daily. Ambulatory BP measurements were performed at start and after 1 and 6 months of Four males (aged 10 to 15) were evaluated for systolic blood pressures consistently above treatment. the 99.6th centile. All were overweight with BMI ranging from 27-35. Clinical RESULTS: 94 (85,5%) patients completed the six months ramipril therapy. Reduction in examinations, renal ultrasound and DMSA scans were normal. Plasma electrolytes, renin, 24-hour mean arterial pressure (MAP) was 4,95 mmHg (-1,02 SD) after 1 month and 10,14 aldosterone, cortisol, testosterone, ACTH and TSH were normal. 24 hour urinary steroid mmHg (-2,05 SD) 6 months treatment respectively. BP was reduced with equal efficacy profiles showed a generalised excess of adrenal androgen and cortisol metabolites in all during day- and night time. 3/110 (2,7%) patients were lost during the follow-up. Eleven cases (Table). Relevant recognised disorders of adrenal androgen and cortisol metabolism patients (10%) received second antihypertensive medication because of the blood pressure were excluded (Cushing’s disease, 11-â-hydroxylase deficiency, 17-á- hydroxylase remained uncontrolled. (7 pts metoprolol, 4 pts amlodipine) 8 (7,2%) patients suffered deficiency, dexamethasone-suppressible hyperaldosteronism and apparent mineralocorticoid recurrent cough, but other side effect has not observed. excess). The four children needed between 2 and 4 different antihypertensives to control CONCLUSION: The ramipril is effective and safe blood pressure lowering therapy and it their hypertension. has additional beneficial metabolic effects in children with obesity related primary hypertension. DISCUSSION Csabi et al (J Endocrinol Invest 2000; 23:435-9) also found elevated urinary cortisol metabolite excretion in hypertensive obese children. These results support the previous findings and provide new data on abnormal urinary adrenal androgen excretion in similar patients. Further studies are required to determine the relationship between obesity, hypertension and the observed abnormalities of urinary steroid excretion.

COD. PP 287 COD. PP 288 Improved control of hypertension in children after renal Long-term follow-up of renovascular hypertension manifested with transplantation cardiomyopathy in young children T Seeman, E Simkova, J Kreisinger, K Vondrak, J Dusek, P Dvorak, J Janda JH Lee (Presenting Author), MK Lee, WK Jhang, YH Kim, YS Park, JK Ko, IS Park Department of Pediatrics , University Hospital Motol, Charles University Prague , 15006 Department of Pediatrics, Asan Medical Center, University of Ulsan, College of Medicine, Prague , Czech Republic Seoul, Korea Asan Medical Center , Department of Pediatrics, Asan Medical Center Pungnap 2(i)-dong Introduction: arterial hypertension is a known risk factor for impaired graft as well as Songpa-gu , 138-736 Seoul , South Korea patient survival in patients after renal transplantation (RTx). However, control of hypertension in transplanted children is unsatisfactorily low – 50-80% of children treated Introduction: We report the long-term follow-up of renovascular hypertension (RVH) with with antihypertensive drugs still have hypertension (i.e. have uncontrolled hypertension). cardiomyopathy in young children. The aim of this interventional study was to improve BP control in children after RTx. Case 1: An eleven-month-old girl was admitted due to cardiomegaly detected on simple Methods: in 36 children after RTx ambulatory blood pressure monitoring (ABPM) and GFR chest X-ray. Blood pressure (BP) was 192/113 mmHg. Creatinine was 0.5 mg/dL. evaluation (Schwartz) were performed. In children with uncontrolled hypertension, the Echocardiography revealed dilated cardiomyopathy. Right renal artery stenosis (RAS) was number of antihypertensive drugs was increased to reach the goal BP <95th centile. ABPM found on conventional angiography (CA). Right relative renal function (RRF) was 16%. was repeated after 12 and 24 months. Balloon angioplasty failed. Hypertension was controlled with ACE inhibitor (ACEI) and Results: after 24 months daytime and night-time BP decreased (from +1.57 to +0.88 SDS diuretics. After 4 years of follow-up, creatinine was 0.5 mg/dL and right RRF was 19.9%. for night-time systolic BP and from +1.10 to +0.35 SDS for night-time diastolic BP, Case 2: A twenty-three-month-old boy was admitted due to anorexia, lethargy and weight p<0.05). The prevalence of uncontrolled hypertension decreased from 42% to 25% (NS). loss. BP was 190/141 mmHg. Creatinine was 0.4 mg/dL. Echocardiography revealed dilated Number of antihypertensive drugs increased from 2.1 to 2.7 drugs per patient (p<0.01), cardiomyopathy. Bilateral RAS was found on CA. Right RRF was 19.5%. Balloon namely that of ACE-inhibitors and diuretics (p<0.01). GFR decreased from 75.5 to 71.9 angioplasty was ineffective. Hypertension was controlled with ACEI, calcium channel ml/min/1.73m2 after 12 months but remained stable during the second year. Proteinuria blocker and diuretics. After 9 years of follow-up, creatinine was 0.8 mg/dL and right RRF decreased from 256 to 134 mg/m2/day (p<0.05). was 20.3%. Conclusion: this is the first prospective interventional trial on treatment of hypertension in Case 3: A seventeen-month-old girl was admitted for the evaluation of hypertrophic children after RTx. We demonstrated that the control of post-transplant hypertension can be cardiomyopathy which was found after detection of heart murmur. BP was 200/100 mmHg. improved by increasing the number of antihypertensive drugs, namely ACE-inhibitors and Creatinine was 0.2 mg/dL. Stenosis of the upper segmental branch of the right renal artery diuretics. Moreover graft function stabilized and proteinuria decreased during the second was found on CA. Right RRF was 17%. Hypertension was controlled with ACEI. After 8 year. years of follow-up, creatinine was 0.6 mg/dL and right RRF was 16%. Supported by grant of Ministry of Education Czech Republic No. 0021620819. Conclusioin: RVH can be manifested as a cardiomyopathy especially in young children. Long-term use of ACEI controlled RVH successfully without deterioration of renal function.

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COD. PP 289 COD. PP 290 Hypertension induced reversible posterior encephalopathy syndrome USE OF AMBULATORY BLOOD PRESSURE MONITORING IN V Askiti, A Mitsioni, J Nikas, S Mastro yanni, E Katsarou, CJ Stefanidis CHILDREN AFTER KIDNEY TRANSPLANTATION , Thivon and Levadias Str, Goudi , 11527 Athens , Greece D Paripovic,G Milosevski,M Kostic,D Kruscic,B Spasojevic,M Stanic,A Peco-Antic University Children’s Hospital, Belgrade Reversible posterior encephalopathy syndrome (PRES) is a recently described acute , Vo jvode Milenka 52/7 , 11000 Belgrade , Serbia Serbia & Montenegro encephalopathy with typical reversible radiological findings of bilateral grey and white matter abnormalities suggestive of oedema in the posterior regions of the cerebral Background: Pediatric kidney transplant recipients are a high-risk population for hemispheres. The causes are miscellaneous, the commonest being abrupt increase in blood hypertension and especially for nocturnal hypertension. The aim of this study was to pressure and treatment with immunosuppressive drugs. PRES is rare in children. Two ascertain the use of ambulatory blood pressure monitoring (ABPM) for assessment of blood children with end stage renal disease and hypertension induced PRES are presented. pressure (BP) in pediatric patients after renal transplantation. Results: Patient 1, a boy 11 year old, on hemodialysis, admitted because of severe Methods: We performed ABPM in 26 transplanted pediatric patients. ABPM was carrie d headaches, generalized seizures and abrupt elevation of blood pressure. Brain computed out using an oscillometric device (SpaceLab 90207) with appropriate cuff size on non- tomography scan (CT) revealed low density areas in the parietal lobes. Magnetic resonance dominant arm. The monitor was programmed to measure blood pressure every 15 min imaging (MRI) disclosed hyperintense cortical-subcortical lesions in the parietal lobes on during the day (6 am to 10 pm) and every 30 min during the night (10 p.m. to 6 am). T2 weighted and FLAIR sequencies. Patient 2, a boy 3 year old, on peritoneal dialysis, Hypertension was defined as a mean systolic and/or diastolic BP during the day and/or admitted because of generalized seizures and acute hypertensive crisis. MRI demonstrated night above the 95th percentile. Casual BP measurements were performed either at home or hyperintense occipital and cerebellar white matter lesions, subcortical white matter lesions during the clinical visit. in both occipital lobes, capsula, corpus callosum, left candate nucleus, posterior thalamus, Results: ABPM was available for analysis in 26 pediatric patients aged from 6 to 19 years putamen and left hippocampus. Both patients were treated with anticonvulsants and a (18 males and 8 females, age 14.5 ± 3.3 years) 3.1±2.6 years after renal transplantation. combination of multiple antihypertensive drugs. Follow-up brain CT scan and MRI, 40 and Hypertension was found in 50% of patients by casual BP and in 85% by ABPM. 52% o f 20 days conversely after treatment on patient 1 and patient 2, showed complete resolution of children showed both day and night hypertension, 38% had isolated night hypertension and the abnormal lesions which confirmed the diagnosis of PRES. Conclusions: Pediatric 4% had isolated daytime hypertension. 31% of patients had nocturnal hypertension while nephrologists must be aware of PRES since early diagnosis, appropriate therapy and their casual BP was normal. Abnormal dipping (<10%) was found in 81% of patients. removal of any offending medication might prevent progression to irreversible brain Conclusion: ABPM is a valuable method which enables detection of nocturnal hypertension damage. and it should regularly be applied in patients with renal grafts.

COD. PP 291 COD. PP 292 Essential hypertension in overweight and obese youth is associated with Endothelial function in adolescents and young adults with white-coat hyperuricemia and impaired endothelial function hypertension M Mraz*, D Potocekova, P Olexa, P Spurny, L Podracka, T Baltesova M Mraz*, D Potocekova, P Olexa, P Spurny, L Podracka, T Baltesova Safarik University , 1-st Department of Paediatrics, Tr. SNP 1 , 040 66 Kosice , Slova k Safarik University , 1-st Department of Paediatrics, Tr. SNP 1 , 040 66 Kosice , Slova k Republic Republic

AIMS: To evaluate the relationship between newly diagnosed essential hypertension (EH), AIMS: To evaluate endothelial function in adolescents and young adults with white-coat established markers of cardiovascular risk and endothelial function in overweight and obese hypertension (WCH) and normotension (NT). METHODS: The study group included 20 adolescents and young adults. METHODS: The study group included 63 subjects with subjects with WCH (10 males, 10 females) aged 19,5 ± 3,7 years and 40 NT controls (17 overweight or obesity (36 males/27 females, aged 19,8 ± 4,2 years, BMI 29,3±3,4 kg/m2). males, 23 females) aged 20,8 ± 3,5 years, matched for gender, age and body mass index. All subjects underwent 24-hours ABPM. According to the ABPM, 25 patients were The patients with overweight, obesity, smoking habit, dyslipidemia, diabetes mellitus and classified as having mild to moderate EH, whilst 38 subjects were normotensive (NT). The essential hypertension were excluded from the study. All subjects underwent office blood patients with smoking habit, diabetes mellitus, secondary hypertension and antihypertensive pressure measurements and 24-hours ABPM. WCH was defined as office hypertension with treatment were excluded. Total cholesterol, HDL, LDL, triglycerides, uric acid, creatinine ABPM normotension. Endothelial function was evaluated using brachial artery flow- and glucose levels were analyzed in fasting blood samples and urinary albumin excretion in mediated dilation (FMD). Maximal artery dilation response up to 180 seconds after cuff 8-hours urine samples. Endothelial function was evaluated using brachial artery flow- release (peak FMD, %) was assessed. Total cholesterol, HDL, LDL, triglycerides and uric mediated dilation (FMD). Maximal artery dilation response against baseline diameter up to acid levels were analyzed from fasting blood samples. RESULTS: No significant 180 seconds after cuff release (peak FMD, %) was assessed. RESULTS: Serum uric aci d differences were found in peak FMD response between WCH and NT groups (14,31±4,47 levels were significantly higher in EH than NT subjects (381±92 umol/l vs. 337±72 umol/l, % vs. 15,48±5,47 %, respectively, p=0,36). Moreover, no significant differences were foun d respectively, p=0,02). No significant differences were found in serum lipids, creatinine, in serum lipid profiles and uric acid levels between WCH and NT groups. fasting glucose and urinary albumin excretion between EH and NT groups. Peak FMD CONCLUSIONS: Adolescents and young adults with WCH without other cardiovascular response was significantly lower in EH group when compared with NT group (5,49±4,83 % risk factors do not show endothelial dysfunction and therefore bear no more risk of vs. 12,75±3,47 %, respectively, p<0,0001). CONCLUSIONS: Newly diagnosed EH in premature atherosclerosis than their healthy counterparts with normal blood pressure. overweight and obese youth is associated with hyperuricemia and endothelial dysfunction. Hyperuricemia may therefore play a causal role in the pathogenesis of EH and contribute to endothelial dysfunction and early-onset atherosclerosis in overweight and obese adolescents and young adults.

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COD. PP 293 COD. PP 294 AMBULATORY BLOOD PRESSURE MONITORING IN HEALTHY PROTRACTED FEBRILE MYALGIA RESENTING AS SCHOOLCHILDREN WITH A FAMILY HISTORY OF POLYARTERITIS NODOSA

HYPERTENSION Z Bircan, S Tugay E Baskin*, B Malbora, PI Agras, E Melek, N Cengiz, Y Uslu, H Sakalli, Haberal M Dept o f Kocaeli University Faculty of Medicine Pediatric Nephrology Department Umuttepe , Pediatric Nephrology, Baskent University, Ankara, Turkey [email protected] , 41380 Kocaeli , Turkey Baskent University hospital , Dept of Ped Nephrology 6.cadde 72/3 , 06490 Ankara , Turkey The insidious onset of unexplained fever, weight loss, skin lesions, abdominal pain and musculoskeletal pain should suggest the diagnosis of polyarteritis nodosa (PAN). Protracted The presence of positive family history increases the risk of development of primary febrile myalgia (PFM) should be kept in mind in the differential diagnosis because PAN hypertension. Phycisians must pay great attention to following up the children with positive and HSS has been reported 2% coincidentally in Familial Mediterranean Fever (FMF). In family history for primary hypertension. Ambulatory blood pressure monitoring (ABPM) this report four cases of PFM presenting as PAN will be described. may be more helpful to detect BP levels before HT becomes clinically overt. We aimed to 11, 15, 8 and 6 year old boys presented with severe mucle pain and abdominal pain lasting investigate the ABPM findings of healthy school children with and without positive family longer than 15 days. Shared past medical history included recurrent febrile abdominal pain history of hypertension or arthritis. Physical examination revealed stage 2 hypertension together with severely Seventy-nine healthy school children were included in the study. The mean age was 14.0 sensitive muscles. Laboratory examinations revealed high acute phase reactants, normal 1.9 (10-18) years. Family history for primary hypertension was determined by a duplex renal USG, negative p-ANCA, normal creatine kinase and complement levels. All questionnaire. There were 39 children (14 female, 24 males) with positive familial history these patients were hospitalized with the diagnosis of PAN and one of them went on to of primary HT [PHT (+) group] and 40 children (17 female/23 male) without familial renal angiography which was normal. With a single day steroid therapy, all the severe history of HT [PHT (-)] group. ABPM was performed in all subjects and findings were symptoms subsided together with hypertension in all the cases. evaluated. ABPM findings evaluated as overall day, awake and asleep revealed that the In the light of this case reports it is concluded that PFM is a common feature of FMF mean systolic, diastolic and mean arterial BP were significantly higher in PHT(+) group mimicking PAN in childhood. Hypertension is usually accompanied as a result of than in PHT (-) group (p<0,05). These differences persisted when the effect of BMI was sympathetic discharge because of severe myalgia. Prednisolone is the drug of choice and eliminated by univariate analysis. In PHT (+) group, systolic BP and diastolic BP load were sudden recovery is the main differentiating factor from PAN. significantly higher than HT (-) group (p<0, 05). The results of our study revealed that healthy children with positive family history for HT have significant changes in blood pressure parameters demonstrated by ABPM. In these children, ABPM will be useful to determine the children at risk of developing hypertension more effectively and take the preventive measures at an early age.

COD. PP 295 COD. PP 296 TAKAYASU ARTERITIS IN CHILDREN: PRELIMINARY OBESITY RELATED HYPERTENSION AND RENAL FUNCTIONS EXPERIENCE WITH CYCLOPHOSPHAMIDE INDUCTION IN CHILDREN FOLLOWED BY METHOTREXATE FOR MAINTENANCE E Temel, O Soylemezoglu, E C›ng›, E Ozgur, A Bideci,M Unlu . Presenting author: E TREATMENT Temel A Duzova, Y Bilginer, S Ozen, R Topaloglu, N Besbas, A Bakkaloglu GAZÝ UNÝVERSÝTY SCHOOL OF MEDÝCÝNE DEPARTMENT OF PED ÝATRÝC Hacettepe University Faculty of Medicine , Hacettepe Univ. Faculty of Medicine, Dept. of NEPHROLOGY , GAZÝ UNÝVERSÝTY HOSPÝTAL DEPARTMENT OF PED ÝATRÝC Pediatrics, Pediatric Nephrology and Rheumatology Unit , 06100 Ankara , Turkey NEPHROLOGY BESEVLER , 06500 ANKARA , Turke y

Background: Takayasu Arteritis (TA) is the vasculitis of aorta and its main branches. A Various abnormalities have been suggested to alter renal function in obesity including hypertension, hyperinsulinemia, insulin resistance and structural changes within the kidney. high relapse rate is observed in adults with various treatment protocols. Aim: We aimed to review our experience with cyclophosphamide (CYC) induction The aim of this study is to evaluate the renal functions and investigate the various factors followed by methotrexate (MTX) for maintenance treatment in the last 7 years. contributing to hypertension in obese children. A total of 31 obese children (ages: 6-16 Patients and Method: Six patients (4 F, 2 M; with an age range of 12-17 years) were years) with body mass index above 95th percentile were included in the study. Sixteen of diagnosed as TA according to the recently suggested criteria for childhood TA. Two were the patients were found to be hypertensive with ABP-monitoring. Although the estimated siblings. Five had involvement of both the thoracic and abdominal aorta. Headache and GFR was increased in all patients (>130 ml/min), no statistical difference was observed abdominal pain were the leading symptoms. One was erroneously diagnosed as Crohn’s between the hypertensive and normotensive group. Plasma renin levels were found to be disease whereas in two the diagnosis was delayed since they were suspected to have higher in the hypertensive group (26.8±21.2 vs. 17.1±16.15 pg/ml, p>0.05). Urinary familial Mediterranean fever. Acute phase reactants were elevated in all except for the girl albumin excretion, serum lipid parameters, the fasting glucose concentrations did not differ on colchicine. One patient died due to pulmonary vasculitis at the first month of therapy. in both groups, but the fasting insulin levels were higher in the hypertensive group The remaining four with involvement of both the thoracic and abdominal aorta and (18,7±14,7 IU/ml versus15±8,5 IU/ml, p>0.05). No correlation was observed with branches received steroids with oral CYC (oral) for 12 weeks followed by weekly MTX for microalbuminuria, insulin resistance and blood pressure values. Dyslipidemia was not 12-18 months. One patient who had vasculitis of the abdominal aorta and renal artery, prominent in the study population and the dynamic renal scintigraphy findings did not received steroid + MTX. reveal any difference among the groups. Results: All entered remission. Aortic bypasses were performed in two whereas aorta-renal bypass was performed in the other two patents. In one patient the contra-lateral renal artery The most prominant findings were the hyperfiltrative state of the kidneys and the stenosis was managed by a balloon dilatation and unilateral nephrectomy had to be hypertension in half of our patients. Limitations of the study are the study population who performed in another one. One had a relapse at one year with re-stenosis of the graft. There were admitted for the first time and the short follow-up period. More follow-up till the were no side effects and all patients were fine at their last visits. adulthood should be done to observe the renal effects of obesity and hypertension including Conclusion: The presented single-center experience suggests that CYC induction followed the renal histology and cardiovascular changes by MTX is an effective and safe treatment for childhood TA. Large, multicenter studies are needed to confirm this observation.

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COD. PP 297 COD. PP 298 CARDIAC FUNCTIONS IN OBESITY RELATED HYPERTENSION Obesity hypertension as a component of the metabolic syndrome O Soylemezoglu, E Temel, E Ozgur, S Tunaoglu, P Cinaz, S Bakkaloglu, K Fidan, N J Putnik, N Stajic, A. Licanski, D Zdravkovic, T Milenkovic, S Zivanovic, M Djordjevic, R Buyan. Presenting author: E Temel Bogdanovic Institute for Mother and Child Health Care, Belgrade Gazi University Hospital Pediatric Nephrology , Besevler, , 06510 Ankara , Turke y Institute for Mother and Child health Care , Radoja Dakica 6 , 11070 Belgrade , Serbia Serbia & Montenegro Obesity initiates a complex cascade of renal and cardiovascular disorders such as hypertension, atherosclerosis, hyperlipidemia and cardiomyopathy. The aim of this study is Metabolic syndrome is often defined as having any three or more of the following: obesity, to evaluate the cardiac functions along with the presence of hypertension in obese children. hypertension, high triglyceride, low HDL cholesterol and high blood glucose levels. The study included 50 obese (BMI above 95th percentile) and 20 normal weighed children In the last 12 months we examined 16 obese and hypertensive children and adolescents who as the control group. The APB-monitoring revealed %54 hypertensive children in the obese fullfilled criteria for the metabolic syndrome. group. Dyslipidemia was not observed in the study groups. The echocardiographic Obesity was defined as a body mass index (BMI) at or above the 95th percentile for age and measurements revealed the deteoriated systolic and the diastolic cardiac functions in the sex. Hypertension was confirmed by ambulatory blood pressure monitornig (ABPM). The obese group. The mitral atrial contraction and mitral early filling phases were significantly criteria for dyslipidemia were triglycerides level above 1,24 mmol/l and HDL cholesterol lower (0.76±0,27 vs 0.81±0.20 m/s; 1.19±0.19 vs 1.33±0.15 m/s); while the left ventricular below 1 mmol/l. Impaired glucose tolerance was defined as fasting blood glucose above 6,1 systolic and diastolic diameters (2.61±0.43 vs 2.17±0.45 cm; 4.21±0.54 vs 3.68±0.31 cm), mmol/. The two hour oral glucose tolerance test (OGTT) was performed and the criterion diastolic intraventricular septum diameter (1.00±0.19 cm vs 0.84±0.12cm), end-diastolic for hyperinsulinemic response was base insulin level above 20 IJ/ml and above 100 IJ/ml volume (77.53±22.54 ml vs 56.99±10.06 ml) were higher in the obese children comparing during the test. to the control. The hypertensive obese children had significantly lower diastolic left Females and males were represented equaly, with mean age 15,4 years. One third ventricule diameter (4.04±0.58 vs 4.40±0.43 cm) comparing to the normotensive group. The complained on headache. All of them were obese and hypertensive, 6/16 (38%) had one BMI of the obese patients had a positive correlation with the diastolic intraventricular more crtierion for the metabolic syndrome, 7/16 (43%) had four, and three of them (19%) septum diameter, systolic and diastolic posterior ventricular wall diameters, whereas a had all five criteria. None had electrocardiogram abnormalities, but two had first stage of negative correlation with left ventricule wall stress. hypertensive retinopathy. Hyperinsulinemic response was present in 56% of patients. All had normal GFR, 40% was hyperuricemic. Microalbuminuria measured in 6 pts was The results of this study demonstrate the high prevalance of hypertension and the cardiac elevated in 3. dysfunction in childhood obesity. The cardiac functions are affected even in the absence o f Obese and hypertensive children often have other components of the metabolic syndrome the risk factors. Therefore children with high body mass indexes should be evaluated and each of them is considered to accelerate atherosclerosis and development of carefully for possible cardiovascular complications. cardiovascular diseases. Therefore complete clinical and laboratory evaluation of obese children is necessery

COD. PP 299 COD. PP 300 DIFFERENT PREVALENCE OF HYPERTENSION IN SCHOOL- Laboratory Studies and Bone Densitometry as Markers of Bone Disease AGED CHILDREN ACCORDING TO DIFFERENT BLOOD in Children with CRF PRESSURE MEASUREMENTS M Zahrane; H Basaraa; A Esmael; Pediatric and Radiology Department*, Faculty of C. Corrado, M. M. D’Alessandro, F. Leone, G. Pavone, M.C. Sapia, S. Maringhini Medicine, Cairo University presenting author: Mona zahrane Nefrologia pediatrica. Ospedale G. Di Cristina. Palermo , 8 tolombat street ,Garden-City,2nd floor,Cairo-Egypt , 567 Cairo-Egypt , Egypt nefrologia pediatrica Ospedale G Di Cristina , piazza motalto , 90100 palermo , Italy Renal osteodystrophy encompasses a variety of skeletal disorder ranging from high turnover Aim of the study: In the last years hypertension (HYT) in children is increased. The lesions of secondary hyperparathyroidism (SHPT), to low turnover lesions, 53 children aged definition of HYT is based on the normative distribution of blood pressure (BP) in healthy (11 3.84) years, 17 on conservative treatment and 36 on haemodialysis were included in children. Accurate measurement of BP is difficult. Aim of this study was to compare two the study. BMD of lumbar spine and wrist were measured by (DEXA) and compared with different BP measurements; auscultatory (A) or oscillometric (B). age and sex matched controls, Our results shows that out of 53 patients, 25 (47%) are Methods: We registered age, height, weight in 422 children of primary and secondary osteopenic 22 (88%) on haemodialysis and 3 (12%) on conservative treatment, of these 13 school-children (6-14 years old). We measured blood pressure with clinical (24.4%) had severe osteopenia as regard BMD of the spine, while DEXA wrist shows 11 sphygmomanometer and with automatic oscillometric device OMRON. In both we used (21%) are osteopenic, 7 (64%) on regular haemodialysis and 4 (36%) on conservative III, of appropriate cuff in relation to upper arm size. A multivariate analysis of data was performed these 3 (5.66%) had severe osteopenia ,correlation between Z-score spine in the osteopenic using SPSS software package. group and different biochemical parameters shows non significant correlation except –ve Results: According to the SOMU formula prevalence of hypertension was found in 28% of correlation with duration and age of the patients, while Z-score wrist of the same group children using A measurements and in 21% using O devices. BP values were mean values shows +ve correlation with bicarbonate. our result shows that group with IPTH > 200 pg/ml of two measurements repeated in 15 minutes. are more osteopenic than those with lower IPHT levels, although difference did not reach BP values were directly related with age (p<0.001) and BMI (p<0.001) in both conditions. level of statistical significance P > 0.05,. We can conclude that osteopenia is frequent in When we divided our children according to their ages < 10 years (1) and >10 years (2) we patients with CRF more in the dialysed group, with longer duration of the disease, older age found: and severe acidosis, irrespective of the severity of the disease. Although, degree of 1: Systolic BP 113.7± 13.9 vs 106.3 ± 15 mmHg with A and O respectively (p< 0.05) ostopenia is not correlated with biochemical findings of (SHPT) but still patients with 1: Diastolic BP 66.7± 10.3 vs 61.4 ± 13.5 mmHg with A and O respectively (p<0.05) (SHPT) are more osteopenic and have lower cortical bone density 2: Systolic BP 116± 12.4 vs 116 ± 13.7 mmHg with A and O respectively (p: NS) 2: Diastolic BP 61.5± 7.4 vs 61.4 ± 10.7 mmHg with A and O respectively (p: NS) Conclusion: According to the Guidelines auscultation is the recommended method of BP measurement in children, while oscillometric devices must be validated. In our data BP values were different from those obtained by auscultation in children < 10 years. In this group the automatic devices minimize the observer bias.

Pediatr Nephrol (2006) 21:1493–1635 1597

COD. PP 301 COD. PP 302 Vitamin-D-induced vascular calcification in uremic rats is associated Bone mineral density and response to furosemide stimuli in children with Mg2+ accumulation with idiopathic hypercalciuria SC Verberckmoes 1, V Persy 1, GJ Behets 1, D Müller 2, D Haffner 2, ME De Broe 1, PC M D Rodrigo Jiménez*, Mª Isabel Luis Yanes, Mª J Hernández González, M. Monge D’Haese 1 ,U Querfeld 2 1 Department of Physiopathology, University of Antwerp, Zamorano, E Barrios, V García Nieto Unidad de Nefrologia Pediatrica, Hospital Belgium 2 Department of Pediatric Nephrology, Charité University, Berlin, Germany Universitario Nuestra Señora de Candelaria, Tenerife. *Hospital Son Dureta, Palma de Charité Universitätsmedizin Berlin , Campus Virchow Klinikum , 13353 Berlin , Germany Mallorca, Spain Germany Hospital Universitario Ntra. Sra. de Candelaria , Unidad de Nefrologia Pediatrica , 38010 Santa Cruz de Tenerife , Spain Uremia and Vascular calcifications (VC) were induced in rats by either a 4-week adenine treatment followed by a 10-week high (1.03%) phosphate diet (N=13) or 5/6 nephrectomy Bone mineral density (BMD) is reduced in approximately 40% of children with idiopathic followed by 6 weeks of 0.25 ng/kg/d calcitriol treatment in combination with a high (1.2%) hypercalciuria (IH). Blood monocytes isolated from IH patients (or individuals with IH) phosphate diet (N=12). Multi-element mapping for calcium and phosphorus and mineral tend to produced significantly more cytokines that would increase osteoclastic activity, and identification was performed on several regions of 10 µm-thick aortic sections by means of produce a reduction in BMD. Nevertheless, an acidification defect would also contribute to synchrotron µ-X-ray-fluorescence and -diffraction. Bulk calcium and magnesium content of the reduction of BMD. the aorta was assessed using flame atomic absorption spectrometry. Patients and Methods. We have studied 60 children (25M, 35F) affected of IH, with an age Based on the diffraction data the Von Kossa positive precipitate in the investigated aortic of 10.2±3.2 years (range: 3-18). Bone mineral densitometry (Hologic QDR 4500 SL regions (N=38) could be divided into three groups: (i) an amorphous precipitate in the densitometer; DEXA) and an acidification test (1 mg/kg of oral furosemide) were carried absence of any diffraction peak pattern (N=12); (ii) poorly crystalline apatite (N=16); (iii) a out in all children. We considered acidification defect when the minimum pH was above combination of apatite and whitlockite (N=10). As assessed by Chi-square analysis, the 5.35, and osteopenia when Z-BMD was smaller than -1. occurrence of these precipitates significantly differed between the two models. Moreover, Results. Children that did not acidify with furosemide stimuli (Group A, n=13; 21.7%) had the combination of apatite and whitlockite was exclusively found in the 5/6 nephrectomized values in the urinary elimination of titratable acidity (TA) more reduced than those that did calcitriol-treated animals. In the latter animals a significantly increased bulk acidify (Group B) (8.2±4.8 vs. 18.1±10.3 µEq/min/1.73 m2, p=0.003), although differences magnesium/calcium content of the calcified aortas was found as compared to the adenine in the ammonium elimination (NH4+) were not observed. Group A children had Z-BMD treated rats. values reduced compared to those of Group B (-1.07±0.87 vs. -1.62±0.77, p=0.04). A direct These data suggest that in adenine/phosphate-induced uremia-related VC calcium-apatite is relationship between TA and BMD (r= 0,3; p=0.02) and between TA and calcitriol levels the main component of the mineral phase. The presence of the magnesium-containing (r= 0.41, p=0.03) was observed. mineral whitlockite, only found in the vitamin-D-induced model of VC, suggests a Conclusions. The acidification defect after furosemide stimuli is a marker of BMD disturbed magnesium-metabolism to be involved in the pathogenesis of calcifications reduction risk in children with IH. It is difficult to establish the causal relationship between induced by calcitriol-treatment. both parameters, although a partial acidification defect could increase the bone resorption.

COD. PP 303 COD. PP 304 Vascular dysfunction in pathogenesis of osteopenia in children with HEIGHT GROWTH AND BONE MINERAL CONTENT IN chronic interstitial kidney diseases with arterial hypertension CHILDREN WITH IDIOPATHIC NEPHROTIC SYNDROME (INS) N Kartamysheva , A Sikatchev , T Sergeeva , A Kucherenko , A Tsygin , I Smirnov , O G Conti, R Chimenz, L Silipigni, E Di Tommaso, F La Torre, R Gallizzi, C Fede Paediatric Chumakova , Research Centre of Child Health, Moscow. Nephrology and Dialysis Unit, University of Messina Research Centre for Child Health , Pediatric Nephrology, Lomonosovsky pr. 2/62 , 119991 University of Messina , Nephrology and Dialysis Unit, via Consolare Valeria , 98100 Moscow , Russia Messina , Italy Italy

Aim. To determine the significance of vascular dysfunction in pathogenesis of osteopenia in There is still conflicting evidence on the risk of low height growth and bone mass in children with chronic interstitial kidney diseases. children with INS, requiring long-term glucocorticoid therapy. Materials and methods. We examined 6 healthy children without osteopenia and 16 children In last years (follow-up: 35.5 ± 7 months, range 24-48), we have investigated 24 children with osteopenia including 11 patients with chronic interstitial kidney diseases (5 – with (age:6.8 ± 2.4 years, range 3-12; gender:13 male and 11 female) with steroid-sensitive INS. arterial hypertension (group 1), 6 – without it (group 2)), 5 children without chronic 8/24 children presented frequent relapses (FR) or steroid-dependence (SD) INS. We have diseases (group 3). In all of them the blood level of marker of bone formation osteocalcin, tested clinical (height growth, height growth speed) and laboratory (serum calcium, serum urinary levels of marker of bone resorbtion C-telopeptide and marker of vascular phosphorus, serum alkaline phoshatase, serum parathyroid hormone) indexes. Moreover, we dysfunction molecule of cellular vascular adhesion-1 (VCAM-1) were measured by have effected bone ultrasound densitometry (Osteospace-Medi Link) to calcaneus side. The immunoenzyme assay. bone mineral density is evaluated by BUA (Broad-band Ultrasound Attenuation) and Results. We found an increase of the urinary concentration of VCAM-1 in group 1 measured by db/MHz. (1,44±2,49 ng/mmol of ñreatinine) as compared with healthy controls (0,13±0,016 ng/mmol Only 2 children, affected by SDNS, had during follow-up a progressive decrease of the of ñreatinine p<0,006), with group 2 (0,19±0,06 ng/mmol of ñreatinine, p<0,017), and with bone mineral density (-2SD). Moreover one of the 2 children evidenced a progressive group 3 (0,28±0,18 ng/mmol of ñreatinine). We determined a decrease of the blood level of decrease of the height growth speed (-2SD). The other children did not have a pathological osteocalcin in group 1 (35,58±22,16 ng/ml), ð<0,013 as compared with healthy controls height growth and bone mineral density. There was not significantly correlation with total (124,37±13,52 ng/ml), group 2 (128,97±54,47 ng/ml), and group 3 (168,76±15,35 ng/ml). steroid dosage and number of relapses. The laboratory values were regular. The decrease of the urinary concentration of C-telopeptide was determined in group 1 Our data indicate that the steroid therapy, given with appropriate dosage and time, does not (433,44 ± 231,01 ìg/mmol of ñreatinine), ð<0,009 as compared with healthy controls decrease the height growth and bone mineral density in children with INS. However, the (825,54±22,67 ìg/mmol of ñreatinine), group 2 (1219,43±342,43 ìg/mmol of ñreatinine), children with FRNS and SDNS, requiring long-term steroid doses, may have these and group 3 (1324,9±335,93 ìg/mmol of ñreatinine). complications. For this, it is important to test these indexes to begin other known Conclusion. Vascular dysfunction in arterial hypertension may suppress bone metabolism in therapeutic protocols, that allow to reduce the long-term steroid doses. children with chronic interstitial kidney diseases. 1598 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 305 COD. PP 306 PHYSICAL DEVELOPMENT AND STATE OF BONE IN BOYS AND Growth in pre-pubertal children on long-term dialysis YOUTHS HAVING RECEIVED GLUCOCORTOCOSTEROIDS FOR Presenting author: J C Cansick Other authors: S C Waller D Ridout L Rees NEPHROTIC SYNDROME FOR LOND TIME GREAT ORMOND STREET HOSPITAL , DEPT OF NEPHROLOGY, GREAT S V Baiko Republican Center for Pediatric Nephrology and Dialysis, Minsk, Belarus ORMOND STREET HOSPITAL, GREAT ORMOND STREET , WC1N 3JH LONDON , Republican Center for Pediatric Nephrology and Dialysis , Republican Center for Pediatric UK Nephrology and Dialysis , 220018 Minsk , - Belarus Growth failure is reported to be an important complication for children on dialysis. We 60 boys at the age of 6-16 (28 taking steroids and 32 without) and 13 youths at the age of reviewed the case notes of 35 chidren (23 boys), mean age at inclusion 2.8 years (range 17-25 in the remission (more than 6 months after finish therapy) of chronic 0.25-8.9 years, 17 children under 2 years), who had at least one year on dialysis. Data glomerulonephritis nephrotic forms and 145 healthy male at the age of 6-25 were examined. collection was stopped at 10 years of age, commencement of growth hormone or renal All patients were taking glucocorticosteroids not less than 1 year in the periods of transplantation. exacerbation. The decrease of growth of (SDS height -0,03±1,06, control 0,31±0,89, ð<0,05) was revealed by children with nephrotic syndrome. The least growth was observed The mean height standard deviation score (SDS) at the start of dialysis was –2.06. Growth in the group of children taking steroids at the age of 6-8 and 12-16 years (SDS height - rate was normal, with a median change in height SDS per year of –0.06 (range –1.07- 0,86±0,81 and -0,48±0,76, control 0,31±0,89, ð<0,001 and ð<0,05). The increase of body +2.39); children under two years showed catch-up growth with a median change in height weight ( SDS 1,66±1,41; control 0,28±1,09, ð<0,05) and Kettle II index (SDS 2,21±1,99, SDS in the first year on dialysis of +0.31 (range –0.78-+3.13). control 0,11±1,12, ð<0,05) was observed in this group in comparison with the control group. Mean calcium and ionised calcium levels were approximately at the mid-point and Complaints of pains and fatigue in the back and/or lower extremities were presented by phosphate level just above the mid-point of the respective normal ranges. The median PTH 68,75% of children. 9,6% (7 of 73) had fractures during or after steroid treatment. All level was 1.52 times the upper limit of normal. Growth rate correlated with alkaline episodes happened at the age of 12-15, fractures of metatarsal and metacarpal bones were phosphatase, p=0.001, but no other biochemical or haematological markers. diagnosed most frequent (4 episodes). 4 (30%) of 12 patients taking steroids for more than 5 years had fractions. Our results indicate that normal growth can occur in children on dialysis, with catch-up The decrease of mineral density of lumbar spine (L2-L4) was revealed at the age of 7-8 and growth seen in children under 2 years. This is with an intensive nutritional therapy and 15-16 (BMD 0,53±0,06, control 0,63±0,07 g/sm2, ð<0,01 and 0,84±0,15, control 1,05±0,13 medical therapy aiming to keep PTH within the normal range. g/sm2, ð<0,001) during taking steroids. The age rates of physical growth and development did not differ from the youths of same age but the decrease of mineral density of lumbar spine (BMD 1,0±0,1, control 1,15±0,15 g/sm2, ð<0,05) was diagnosed, at 4 of 12 osteopenia was diagnosed.

COD. PP 307 COD. PP 308 Histomorphometric findings in children prior to the commencement of CHRONIC LDL APHERESIS IN CHILDREN renal replacement therapy R Ponikvar, V Premru, R Žugiã, and J Buturovic S C Waller (1) A Freemont (2) L Rees (1) , Department of Nephrology, University Medical Center , 1000 Ljubljana , Slovenia (1) Nephro-Urology Unit, Institute of Child Health and Great Ormond Steet Hospital, (2) Osteoarticular Pathology, The Medical School, University of Manchester, UK. , c/o Dr L Background. The aim of our report is to present chronic LDL apheresis in 2 children Rees, Nephrology Offices, Frontage Building, Great Ormond Street , WC1N London , UK familial hypercholesterolemia, refractory to dietary and pharmacological intervention. Methods. Patient 1: 29-year woman, began with LDL apheresis (dextrane sulphate columns, The importance and relevance of renal osteodystrophy (ROD) has increased with improving Kaneka, Japan) at the age 13, every 2 weeks, 3 volumes of plasma (8000-9000 ml) patient survival. Little is known of the bone health in children prior to starting renal processed per session, vascular access were peripheral (cubital) veins. Simvastatin 40 replacement therapy (RRT). mg/day. Patient 2: 17-year boy, began with LDL apheresis at the age 6, 2 weeks. Membrane plasma Aim: To estimate the prevalence of renal osteodystrophy and investigate the relationship exchange was used for the first 4 years, followed by Kaneka LDL apheresis system for the between skeletal abnormalities and parathyroid hormone (PTH) levels in children starting last 6 years. Three plasma volumes (6800-7200 ml) were processed per session. Vascular RRT. access: double-lumen hemodialysis catheter for the first 2 years, left forearm AV-fistula later. Atorvastatin 20 mg/day. Methods: Following bone labelling with tetracycline eleven patients with chronic renal Results. Laboratory data for the patient No1 and No2, respectively: total cholesterol before insufficiency, median age 14.6 (range 9.2-17.1) years, underwent bone biopsy at the time o f procedure: 11.4 and 7.9 mmol/L, after: 1.8 and 3.0 mmol/L. LDL cholesterol before insertion of dialysis access or transplantation. PTH levels were recorded for an average of procedure: 8.1 and 8.1 mmol/L, after: 0.8 and 2.0 mmol/L. Time average concentration 1.0 (0.5-1.9) years pre-biopsy. (TAC) of total cholesterol: 7.1 and 6.6 mmol/L, TAC of LDL cholesterol: 5.6 and 5.1 mmol/L. Side effects: bradykinine reactions in a girl, mostly in her younger age, vascular Results: All patients demonstrated abnormal bone histology. access problems in a boy, before AV fistula was created. The girl is still in chronic Three patients (27 %) had low turnover disease, including two approaching an adynamic apheresis treatment (16 years), the boy received cadaveric liver graft after 10 years on LDL classification. Mean PTH levels pre-biopsy were 1.7, 4.0 and 6.5 pmol/L (normal range 0.7- apheresis, at the age of 16. Both are conducting normal and successful life. 5.6 pmol/L). Conclusion. LDL apheresis was very well tolerated extracorporeal procedure which Two patients (18 %) had mixed osteodystrophy; mean PTH levels pre-biopsy were just efficiently lowered serum cholesterol concentrations. above the upper limit of the normal range (ULN); 7.5 and 7.6 pmol/L. The remaining six patients (54 %) had changes indicative of hyperparathyroid ROD; all these patients had raised PTH levels. In three patients PTH levels were between one and three times ULN (11.4, 16.0 and 16.0 pmol/L). In the remaining three patients PTH levels were about four times ULN or greater (21.5, 27.1, and 28.8 pmol/L).

Conclusion: The presence of ROD was ubiquitous in children with severe chronic renal insufficiency. Lower levels of PTH were associated with low turnover bone disease and higher PTH levels with high turnover disease. Pediatr Nephrol (2006) 21:1493–1635 1599

COD. PP 309 COD. PP 310 Short-Term Changes in Growth, Body Composition and Biochemical Short-Term Changes in Growth, Bone Mineral Content and Markers in Children Post-Renal Transplantation Biochemical Markers in Children Post-Renal Transplantation H Maxwell 1 (Presenting Author), R Rashid 2, E Neill 1, W Smith 2, D King 1, A M H Maxwell 1 (Presenting Author), R Rashid 2, E Neill 1, D King 1, A M Wallace, S F Wallace 3, S F Ahmed 1 1 Renal Unit, Royal Hospital for Sick Children, Glasgow, UK 2 Ahmed 2. 1 Renal Unit, Royal Hospital for Sick Children, Glasgow, UK 2 Bone and Bone and Endocrine Group, Royal Hospital for Sick Children, Glasgow, UK 3 Dept of Endocrine Research Group, Royal Hospital for Sick Children, Glasgow, UK 3 Dept of Pathological Biochemistry, Glasgow Royal Infirmary, Glasgow Pathological Biochemistry, Glasgow Royal Infirmary, Glasgow, UK Renal Unit, Royal Hospital for Sick Children, , Renal Unit, Royal Hospital for Sick Renal Unit, Royal Hospital for Sick Children , Renal Unit, Royal Hospital for Sick Children, Dalnair St, Yorkhill , G3 8SJ Glasgow , UK Children, Dalnair St,, Yorkhill , G3 8SJ Glasgow , U K

We studied growth and body composition(BC) using dual energy x-ray absorptiometry We studied 10 children(6M:4F) following renal transplantation (median (DEXA) in 10 children(6M:4F) following renal transplantation (median age:12.0yrs,10th, age:12.0yrs,10th,90th centiles:5.2,13.9). Baseline immunosuppression was prednisolone, 90th centiles:5.2,13.9). Baseline immunosuppression was prednisolone, tacrolimus and tacrolimus and azathioprine. 6 children had previously received peritoneal dialysis for 2.5 azathioprine. Lean Mass(LM) and Fat Mass(FM) were adjusted for height (LM HSDS and years (1.3,6.3). At 0 and 6months growth was measured by anthropometry and bone mineral FM HSDS). Regional distribution of FM was expressed as percentage of predicted trunk:leg content(BMC), measured by dual energy x-ray absorptiometry, was calculated for total ratio(ppFR). Serum Leptin, Adiponectin, Interleukin-6(IL-6) and highly sensitive C reactive body (TB) and Lumbar spine (L2-L4) (LS). BMC was adjusted for height age and protein(CRP) were measured. expressed as percentage predicted Height BMC (ppHBMC). Biochemical markers bone Median Ht SDS and Ht velocity at 0 months were –1.7(-3.0,-0.7) and 3.4 cm/yr (1.4,6.1) specific alkaline phosphatase (bAlkP) and total deoxypyridinoline for Creatinine(DPD/Cr) and at 6 months –1.8(-2.9,-0.8) and 4.8 cm/yr (3.2,8.1) respectively. GFR at 6months was were expressed as %change over 6 months. 56ml/min/1.73m2 (46,68). Median %calorie and %protein intake were 97%(84,115) and Median Ht SDS and Ht velocity at 0 months were –1.8(-3.0, -0.7) and 3.4 cm/yr(1.4, 6.1) 98%(91,111) at 0 months and 94%(82,109) and 104%(96,114) at 6 months respectively. and at 6 months –1.7(-2.9, -0.8) and 4.8 cm/yr(3.2, 8.1). GFR at 6months was FM HSDS and LMHSDS at 0months were 1.0(0.1,1.8) and –0.9(-1.5,-0.4) and 1.3(0.6,1.9) 56ml/min/1.73m/2 (46, 68). Median total steroid and tacrolimus dose (mg/kg/day) over the and –0.5(-1.1,0.1) at 6months. Median ppFR was 168%(149,207) and 172%(149,187) at 0 6 month period were 0.6(0.4,0.8) and 0.25(0.1,0.4) respectively. There were no correlations and 6 months. There were no significant changes in FM, LM or ppFR during the study. % between GFR, steroid & immunosuppression doses and BMC or bone markers. increase in Il-2 was significant after 2 months, 66%(31,125) (p<0.05), but not after LSppHBMC decreased between 0 and 6 months, 99%(90,112) and 85%(81,87), p<0.05) but 6months, 13.6%(1.2,18.9). % change at 2 and 6 months were 107%(4,146) and 13.2%(- TBppHBMC, 86%(75, 107) and 81%(75, 86) did not change significantly. %change in 2.1,19.6) for leptin, 13.5%(-4.5,27.6) and –19.5%(-34.2,5.6) for adiponectin, and –18%(- bAlkP over 6months was not significant, –2%(-12, 5.1), but % change in DPD/Cr increased 36,2) and –15%(-28,4) for CRP. There were no correlations between GFR or steroid dose significantly 92.2%(51.3, 109) (p<0.05). There were significant inverse correlations and BC. between %change TB and LS ppHBMC and %change DPD/Cr (p<0.05, r,-0.6) during the In summary, growth is relatively well preserved, with no significant changes in LM or FM. study. Central adiposity is markedly raised before Tx but did not change significantly thereafter. Short term growth after transplantation is relatively normal, but there is a decrease in LS There were no sustained changes in the biochemical markers studied. BMC and correspondingly, a rise in DPD/Cr during the first 6months. No correlation was found with steroid dose.

COD. PP 311 COD. PP 312 Growth, microelements and vitamin status in children given sodium Unusual calcifications in a girl with end-stage renal disease: risk factors polystyrene sulfonate on a long term basis evaluation and treatment. 1 F Cachat F, 2 D Behne Department of Pediatrics, Division of Pediatric Nephrology, P Sorino, T Depalo, V Colella, R Bellantuono, G Messina , F.Puteo, M Giordano, D A University Hospital, Lausanne, Switzerland, and 2 Hahn-Meitner-Institut, Berlin, Germany Caringella Pediatric Nephrology and dialysis Unit, Pediatric Hospital "Giovanni XXIII", Department of Pediatrics, Pediatric Nephrology Unit , Rue du Bugnon , 1011 Lausanne , Bari, Italy Vaud Switzerland Pediatric Hospital "Giovanni XXIII" , via Amendola 207 , 70126 Bari , Italy

Background / aim of the study Unusual calcifications are a new interesting field of research, in both adult and paediatric Sodium polystyrene sulfonate (SPS) po has been used for K chelation in patients with patient population undergoing dialysis. hyperkalemia, but is associated with gastrointestinal side effects. We describe a method o f The presence of uncontrolled secondary hyperparatiroidism (SHPT), elevated serum Ca x P pre-treating the milk with SPS, and also present the long-term growth and product, the use of high dose vitamin D and Ca-containing phosphate binders, are microelement/vitamin status of one patient. traditionally considered as risk factors for the metastatic calcification growth in soft tissues and vessels. New emerging risk factors included: elevated homocysteine levels, chronic Results inflammation, oxidative stress, lack of proteins inhibitors calcification. Two patients had type I pseudohypoaldosteronism and one recessive polycystic kidney We report on a case of a 18-year old girl, undergoing dialysis since she was six because of a disease and hyperkalemia secondary to angiotensin receptor blockers and ACE inhibitor. Wilms bilateral tumor. The patient presented severe and diffused calcification of differen t organs: the peritoneal membrane and intestinal wall, abdominal vessels, cardiac valves and SPS was mixed with milk at a concentration of 3%, and the children were given only the coronary arteries, conjunctive and, unusually, in the limbus. surnatant. The three patients have been able to fully tolerate their daily milk intake, with no Multiple risk factors for the development of calcifications are present in this case: age, gastro-intestinal side effects and a markedly decrease number of hyperkalemia episodes. dialysis duration, SHPT, chronic inflammation, hyperhomocysteinemia, use of coumadin as anticoagulant therapy for central venous catheter. Long-term growth was normal in two patients, and sub-optimal in one. One patient had low The interruption of treatment with coumadin, vitamin D and Ca-containing phosphate levels of selenium and Zinc and vitamin B1, which could not be attributed to SPS chelation, binders together with the improvement of Ca-P metabolism and the use of calciomimetic, except for vitamin B1, as shown by milk analysis: gained the improvement of ocular lesions and prevented the progression of the other unusual calcifications. Milk: Na 11.8 mmol/l, K 22.8 mmol/l, Selenium 0.020 mg/kg, Zinc 5.3 mg/kg Whether or not calcifications could be reversed is not yet known, but exciting new studies suggest that this may be possible in the near future. Milk + SPS3%: Na 72.4 mmol/l, K 6.6 mmol/l, Selenium 0.019 mg/kg, Zinc 3.7 mg/kg

Milk: Vitamin A 181 IU/100 g, B1 0.18 mg/100 g, B2 0.1 mg/100 g, B6 0.03 mg/100 g, B12 0.3 mg/100 g, D3 217 IU/100 g

Milk + SPS3%: Vitamin A 188 IU/100 g, B1 0.05 mg/100 g, B2 0.1 mg/100 g, B6 0.03 mg/100 g, B12 0.5 mg/100 g, D3 164 IU/100 g

Conclusions The decrease in vitamin B1 in SPS-treated milk needs to be confirmed. Pre-treatment of milk with SPS is effective, safe and not associated with major selenium, Zinc or other vitamins deficiencies. The growth of patients given such a diet seems to be normal. 1600 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 313 COD. PP 314 Red Blood Cell Osmotic Fragility in Chronically Hemodialyzed Patients COMPLICATIONS OF INTERNAL CENTRAL VENOUS LINES M Zahrane; A M Kaddeh and A El-Khawaga* Pediatric Department and Chemical (PORTS) IN CHILDREN WITH CHRONIC RENAL DISEASE Pathology Department* Cairo University presenting author: Mona zahrane M Szczepañska1, K Szprynger1, P Stoksik2, A Morawiec –Knysak1, P Adamczyk1, K , 8 tolombat street, Garden- City, 2nd floor -Cairo- Egypt , 564 Cairo-Egypt , Egypt Ziora1, J Oúwiæcimska1 1 Department of Paediatrics, Nephrology and Endocrinology of Childhood, and 2 Department of Clinical Anaesthesiology, Silesian Academy of Medicine, Chronic renal failure induces anemia and short erythrocyte life span. So the Aim of our Zabrze, POLAND study To find the cause of shortened red cell survival in uremic patients and correlate with Department of Paediatrics, Nephrology and Endocrinology of Childhood , ul. 3 Maja different variables. We evaluated the RBC osmotic fragility in 36 chronic hemodialyze d 13/15 , 41-800 Zabrze , Poland patients.. Fifteen healthy volunteers served as controls. Biochemistry, hemoglobin, electrolytes, osmolarity and intact Parathormone and osmotic fragility were examined The application of central venous lines (CVL) in children has been widely accepted in the before and after the dialysis session. The results showed that MOF was significantly greater treatment of paediatric cancer. They are also increasingly used in chronic paediatric in hemodilayzed patients before dialysis than in the control group (0.45 0.03 vs 0.36 patients, in whom the CVL allows continuous access for medications, for parenteral 0.03%). The osmotic resistance to hemodialysis was also recorded after dialysis (0.42 hydration and nutrition as well as for frequent blood sampling. 0.05 vs 0.36 0.03%) comparison between MOF% and different biochemical indices, In the current study, the authors present their experience with subcutaneous port devices in intact parathormone (IPTH) before and after dialysis, shows significant decrease in BUN, eight children with chronic kidney diseases. In these children subcutaneous port devices creatinine, phosphorus, serum potassium and serum osmolarity (P < 0.0001) and significant (totally 9 ports) were applied for a mean of 26.7 months. The mean age at the time of increase in calcium, blood sugar (P < 0.001), also intact parathormone shows significant implantation was 2.2 years, and the mean body weight – 10.6 kg. In all children, it was decrease (P = 0.02) and MOF% shows significant decrease (P = 0.004), correlation analysis increasingly difficult to establish peripheral venous access. showed that the MOF was significantly correlated with urea nitrogen (r = 0.538) , serum In one child, a neck and chest haematoma complicated port implantation. Infectious osmolarity (r = 0.39) and intact parathormone (r = 0.691). In addition the osmotic fragility complications associated with implanted port device were not observed. Thrombotic was significantly higher in patients who had predialysis intact parathormone level > 100 complications occurred in six children with chronic renal failure – in five cases the lumen of pg/dl (P < 0.05). In conclusion hemodialysis can improve the osmotic fragility. The port device has been successfully recanalysed, in three cases this happened even several mechanism underlying this improvement may be the removal of low molecular weight times. In a single child, the thrombus was detected on the tip of CVL. In two children the uremic toxins, resulting in normalization of serum osmolarity. removal of port device was necessary because of CVL breakage and port device thrombosis, respectively. Two children died with functional port devices. The cause of death was not associated with implanted CVL. In conclusion, the application of subcutaneous port devices definitely improved the comfort of treatment but was significantly associated with thrombotic complications. Infectious complications were not detected as compared to haematological patients.

COD. PP 315 COD. PP 316 A comprehensive conservative management of ESRF: Three -year THE ANGIOTENSIN II RECEPTOR 1 BLOCKERS AS ADD-ON dialysis freedom. RENOPROTECTION IN CHILDREN WITH CHRONIC KIDNEY AJ Al Mosawi DISEASE TREATED WITH ACE-INHIBITORS University Hospital in Al Kahimiyia Bagha Iraq PO Box 70025 , Head of the department of M Litwin, R Grenda, J Sladowska, J Antoniewicz pediatrics , 70025 Baghdad , Iraq Iraq THE CHILDREN`S MEMORIAL HEALTH INSTITUTE , DEPT. OF NEPHROLOGY & ARTERIAL HYPERTENSION , 04-730 WARSAW , POLAND Polan d Background: With appropriate dietary and pharmacologic management, patients with non- terminal chronic renal failure (CRF) can be maintained surprisingly well, and the transition The standard renoprotection is based on inhibition of renin-angiotensin-system (RAS) by from non-terminal CRF to en-stage-renal failure ESRF represents a small decrement of angiotensin convertase inhibitors (ACEi) or angiotensin II receptor 1 blockers (AT1B). The renal function resulting in a large physiologic hurdle for the patient. The addition to these aim of our study was to analyze effects of addition of AT1B to ACEi based renoprotection effective traditional measures, an agent enhance fecal nitrogen excretion can possibly in children with CKD stage 2-4. Patients and methods: 11 children, aged 10.8 yrs (0.5 - 18 bridge this gap resulting from this small decrement of renal function obviating the need for yrs) with mean glomerular filtration rate (GFR) 50 ±45 ml/min/1.73m2. In 4 pts the primary RRT for some period of time renal disease was hemolytic uremic syndrome, in 3 congenital nephrotic syndrome (CNS), A novel regimen combining the traditional conservative management of CRF with addition in 3 reflux nephropathy, in 1 acute cortical necrosis. All pts were treated with complex of Acacia gum (AG) 1 g/kg /day has been reported to provide patients with ESRF dialysis hypotensive ACEi- based therapy. AT1B losartan was added in mean dose 0.7 mg/kg/day. freedom. Change in GFR, proteinuria and blood pressure at two 12 months intervals before and after Aim: To describe the longest period of dialysis freedom (3-year) achieved in history with adding AT1B were compared. Results: during 12 mts preceding AT1B therapy there was no this novel form of RRT. change in blood pressure and proteinuria and GFR declined in 9 of 11 pts. At 12-th month Patient and Method: An 11-year-old girl with ESRF who initially required 4 sessions o f of add-on therapy with AT1B there was significant decrease in both absolute and indexed intermittent peritoneal dialysis to control uremic symptoms despite conservative measures. blood pressure values. Proteinuria decreased in 8 pts, did not change in 1 and increased in 2 Thereafter, managed with a novel regimen combining the traditional conservative including one with CNS. GFR stabilized or increased in 8 pts and decreased in 3 pts with management of CRF including low protein diet with addition of Acacia gum (AG) 1 CNS. In 7 of 11 pts there was significant, but not threatening increase in serum potassium. g/kg /day. One year dialysis and improve well- being was achieved [1]. This patient Conclusion: add-on renoprotection with AT1B added to ACEi is safe and significantly continued the previously described regimen for additional two years. improves renoprotective effects of ACEi treatment in children with progressive Results. During these 2 years she continued in experiencing improved well- being and good nephropathies, including pts with advanced CKD. participation in outdoor activities, had never been acidotic or experienced any uremic symptoms.

References

1-Al-Mosawi AJ (2004). Acacia gum supplementation of a low- protein diet in children with

end-stage renal disease. Pediatr Nephrol 19; 1156-1159. Pediatr Nephrol (2006) 21:1493–1635 1601

COD. PP 317 COD. PP 318 Catch-up growth follows an abnormal pattern in moderate A COMPREHENSIVE CONSERVATIVE MANAGEMENT FOR experimental chronic renal failure (CRF). Growth hormone (GH) ESRF: THREE-YEAR DIALYSIS FREEOM. treatment normalizes it. AJ Al Mosawi I Molinos, F Santos, E Carbajo, E García, J Rodríguez, H Gil, O Alvarez-Garcia, V Loredo, University Hospital in al kadhimiyia , Head of the department of pediatrics , 70025 and L Mallada Baghdad , Iraq Hospital Universitario Central de Asturias. Universidad de Oviedo , Pediatria. Facultad de Medicina. Julian Claveria 6 , 33429 Oviedo , Asturias Spain Background: Conservative measures of non- terminal CRF, can only be non-terminal chronic renal failure (CRF) successful in and patients with ESRF can’t sustain life in the Objective. To find out in subjects with CRF and normal longitudinal growth rate if: a) absence of renal replacement therapy. catch-up growth occurs after a transient growth-retarding condition and b) the effect of GH A novel regimen combining the traditional conservative management of CRF with addition treatment on such process. Protocol. Moderate CRF was induced by partial nephrectomy of Acacia gum (AG) 1 g/kg /day has been reported to provide patients with ESRF dialysis (days 0 and 4) in young rats (NX). Normal growth rate was confirmed by similar osseous freedom. front advance, assessed by calcein labeling, in the tibiae of NX and control (C) rats. From Aim: To describe the longest period of dialysis freedom (3-year) achieved in history with days 11 to 13, food intake was restricted in a group of NX and C rats (NXR and CR). After this novel form of RRT. starting refeeding, a group of NXR and CR rats, received GH treatment from day 14 to 20 Patient and Method: An 11-year-old girl with ESRF who initially required 4 sessions o f (NXRGH and CRGH). Rats were sacrificed on days 14 (C, CR, NX, NXR), 17 and 21 (C, intermittent peritoneal dialysis to control uremic symptoms despite conservative measures. CR, CRGH, NX, NXR, NXRGH), and 36 (C, CR, NX, NXR). Results. With refeeding, Thereafter, managed with a novel regimen combining the traditional conservative growth rate of NXR and CR rats became significantly greater than that of C. Catch-up management of CRF including low protein diet with addition of Acacia gum (AG) 1 growth occurred later and with lower growth rate in NXR than CR rats whereas catch-up g/kg /day. One year dialysis and improve well- being was achieved [Published in October growth of NXRGH animals was similar to that of CR rats. Changes in growth rate were issue of Pediatric Nephrology 2004]. This patient continued the previously described associated with modifications in the histomorphometry and proliferative activity of growth regimen for additional two years. cartilage cells. Conclusions. In moderate experimental CRF catch-up growth occurs but Results. During these 2 years she continue in experiencing improved well- being and good with a different pattern from that observed in the presence of normal renal function. GH participation in outdoor activities, had never been acidotic or experienced any uremic treatment tends to normalize the pattern of catch-up growth in CRF. Changes in growth symptoms. A maximum urea level of 127 mg /dl and a serum creatinine of 5 mg/dl were velocity are associated to modifications in the structure and dynamics of chondrocytes. noted during a period of decreases adherence to dietary restriction and less compliance to AG therapy. Conclusion: This is the first paper describing three years dialysis freedom in a child with ESRF.

COD. PP 319 COD. PP 320 Growth hormone (GH) secretory response to ghrelin is preserved in Ghrelin administration transiently increases food intake in young young uremic rats uremic rats but does not result in sustained improvement of food O Alvarez-Garcia, J Rodriguez, E Garcia, H Gil, E Carbajo-Perez, F Santos consumption Hospital Universitario Central de Asturias. Universidad de Oviedo , Pediatria. Facultad de O Alvarez-Garcia, J Rodriguez, E Garcia, H Gil, L Mallada, V Loredo, E Carbajo, F Santos Medicina. Julian Claveria 6 , 33429 Oviedo , Asturias Spain Hospital Universitario Central de Asturias. Universidad de Oviedo , Pediatria. Facultad de Medicina. Julian Claveria 6 , 33429 Oviedo , Asturias Spain Objective. To find out whether ghrelin administration stimulates GH secretion in chronic renal failure (CRF). Materials and Methods. Three groups (n=5) of young rats were used: Objective. To examine whether ghrelin administration stimulates food intake in young nephrectomized fed ad libitum (Nx), sham-operated fed ad libitum (SAL), and sham- uremic rats. Materials and Methods. The lowest intraperitoneal ghrelin dose able to operated pair fed with Nx (SPF). CRF was induced by partial nephrectomy on days 0 and 4 stimulate feeding in young control rats (SAL) was found out by giving injections of saline and confirmed by measuring creatinine and urea nitrogen concentrations. On day 23, 3 nmol or ghrelin (100 pmol, 300 pmol, 1 nmol, 3 nmol, 10 nmol and 30 nmol; n=8-10 animals for of ghrelin were injected intravenously and serum GH concentrations measured by each dose). Food was weighed 2, 4 and 24 hours, thereafter. The resulting ghrelin dose was radioimmunoassay in samples obtained 0, 10, 20, 40 and 60 minutes thereafter. Results. As then administered to young uremic rats (Nx, n=6) with chronic renal failure (mean serum shown in the Figure, basal GH concentrations were similar in all groups. Ghrelin urea nitrogen 4 times above control values). Results. In SAL group, ghrelin significantly administration gave rise to similarly marked elevation of GH levels which were maximal 10 (p<0.05) increased food intake 2 (X±SEM, 1.8±0.2 vs 0.8±0.2 in untreated rats), 4 (2.9±0.4 minutes after ghrelin injection in all groups. Basal GH levels were again reached in SAL vs 1.7±0.2) and 24 (20.0±0.4 vs 18.2±0.7) hours following injection of the 30 nmol dose. and SPF at 40 minutes whereas Nx had not returned to basal GH levels even 60 min after Smaller doses were ineffective. In Nx, the 30 nmol dose of ghrelin increased 2 hour food ghrelin injection. Conclusion. GH secretory response to exogenous ghrelin is preserved in intake (1.3±0.2 vs 0.5±0.2 g, p<0.01), whereas the difference was not significant within the young uremic rats. Delayed return of GH concentrations to basal values in Nx suggests 4 hour postinjection period (1.9±0.2 vs 1.3±0.2 g) and was completely abolished at 24 hours decreased metabolic clearance and prolonged half life of GH in this model of CRF. (12.5±0.6 vs 12.2±0.5 g). Conclusion. Orexigenic ghrelin stimulus is present in young uremic rats but the effect is counterbalanced by a subsequent reduction in food intake. Accordingly, ghrelin is not useful as a therapeutic tool to improve food consumption in this experimental model of chronic renal failure. 1602 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 321 COD. PP 322 Plasma concentrations of total ghrelin are elevated in children with Renal growth factor in Wiedemann-Beckwith Syndrome chronic renal failure (CRF) and correlate with the severity of renal Afanetti M 1, Huynh Ngoc L1-3, Chami L1, Coache C2, Ambrosetti D3, Berard E1. 1 – function reduction Service de Pédiatrie CHU Nice (France); 2 – Hal de Fréjus; 3- Service d’anatomopathologie J Rodriguez, E Garcia, M Fernandez, L Mallada, F Santos CHU Nice. Presenting Author : Afanetti M Hospital Universitario Central de Asturias. Universidad de Oviedo , Pediatria. Facultad de , 2 rue spitalieri , 06000 Nice , France Medicina. Julian Claveria 6 , 33429 Oviedo , Asturias Spain W.., a girl born of un-consanguineous parents, exhibited at birth all signs of Wiedemann- CRF children undergo growth retardation and anorexia. Ghrelin promotes growth hormone Beckwith syndrome (WBS) (Birth weight 5.4kg for 53cm, hypotonia, ombilical hernia, secretion and increases appetite. macroglossia, palpebral angioma, organo-megaly, and hypoglycemia). Caryotype and study Aim. To investigate circulating levels of total and active ghrelin in children with CRF. of chromosome 11 was normal in the family. Moreover, she suffered from a malformative Methods. Eighteen children with CRF and 12 healthy controls were studied. Both groups uropathy. Multicystic non-functional left kidney (length 13cm) was early removed. Right were matched according to body mass index (BMI) and age. Blood nutritional markers kidney (7.6cm at birth) was hyper-echoic with large calices. During the 4 following years, including albumin, glucose, hemoglobin, C reactive protein, prealbumin, and ferritin were follow up was uneventful, with advanced growth (+2.5 SDS) and 3 urinary infections. Right measured. Plasma total and active ghrelin concentrations (pg/ml) were measured by kidney length was +3SDS and 8 large cysts appeared. Creatinine clearance declined to radioimmunoassay using commercial kits (Linco). Intraassay coefficients of variations were 45ml/mn/1.73m². When 4y old, she presented with tumoral aspect of the right kidney and 3.5% and 3.9 %, respectively. adenopathies along renal pedicle. After discussion, Wilms’ tumor was suspected and she Results. Active ghrelin concentrations (X±EEM) were similar in CRF patients (90.3±11.3) received chemotherapy before a 2/3 nephrectomy, only remaining superior right pole, which and controls (90.9±17.4) and did not show correlation with BMI, age or any of the was hyper-echoic and containing 2 large cysts (8 and 15 mm). Pathology showed biochemical variables. Total ghrelin concentrations were higher (p=0.001) in CRF children xanthogranulomatous pyelonephritis (XGP). Her creatininemia was 250µmol/L. (2393.2±326.1) than controls (1057.8±131.6). In control group, total ghrelin concentrations During the following 6 years, she suffered from anemia (EPO requiring), a growth decrease were negatively correlated with age (r = -0.699; p = 0.011) and BMI (r = -0.581; p = 0.048). and further retardation (rhGH requiring). In spite of only 1/6 dysplastic remaining renal In CRF group, total ghrelin levels were negatively correlated with glomerular filtration rate tissue, we observed an increase in kidney length (+2.5cm) and stability of creatinine level. (r = -0.665; p = 0.003) and age (r = -0.538; p = 0.021) and positively correlated with plasma This observation reminds us the possible confusion between Wilms’ tu mor and XGP. It also creatinine concentrations (r = -0.563; p = 0.015). The correlation with BMI was lost. No induces us to search for a factor of kidney growth in WBS. other correlations were found. Conclusions. These results show that total ghrelin, but not active ghrelin, is significantly elevated in plasma of children with CRF and correlates with severity of renal failure. Furthermore, the normal relationship of total ghrelin with BMI is not observed in CRF.

COD. PP 323 COD. PP 324 USEFULLNESS OF A SPECIFIC DATABASE FOR THE STUDY OF Intravenous Iron Treatment in Paediatric Chronic Renal Failure and CHRONIC RENAL INSUFFICIENCY (CRI) IN A DEVELOPING Peritoneal Dialysis Patients not on Erythropoietin COUNTRY HEG Morgan RCL Holt CA Jones BA Judd G Marra, SM Viganò, A Edefonti, M Sandoval*,C Urbina* and F Sereni Pediatric Royal Liverpool Children`s Hospital , Eaton Road , L12 2AP Liverpool , UK nephrology Unit, Policlinico Foundation, Milan *Pediatric Nephrology Unit, “La Mascota” Hospital, Managua BACKGROUND Unit of Pediatric Nephrology, Policlinico Foundation , Via Commenda 9 , 20122 Milan , Intravenous (IV) iron treatment reduces erythropoietin (EPO) dose in paediatric Italy haemodialysis patients. It’s efficacy in paediatric non-haemodialysis patients is less well established. IV iron is routinely given in our institution to these patients including some In the context of a project of development of pediatric nephrology in Nicaragua, data on who have not started EPO. The effect of this strategy was examined. children with CRI were collected in a database since 2002 with the aim of identifying the METHOD causes of CRI and death and analyzing the clinical impact of the project. Patients with chronic renal failure (CRF) or peritoneal dialysis (PD) not on EPO were In the period 2002-2005, 116 cases of CRI (mean age 7.6 ± 5.0 yrs, mean CrCl 43 ± identified. Case notes were reviewed for haemoglobin (Hb), red cell and iron indices for 6 34ml/min/1.73, 73 males) were enrolled: 37 % died, mostly because of complications of months before and at least 3 months after IV iron. ESRD. Since the establishment in Managua of a pediatric HD unit with transplant facilities RESULTS in 2005, 7 children started HD and 4 had a live-related donor transplant. Five patients were identified. Mean age 13.3yr, Mean IV iron (Venofer) dose=3.1 mg/kg. The comparison between Nicaraguan (see figure) and Italian (Italkid) data on CRI shows: Median number of doses=7, range 3-10. Hb increased significantly after IV iron 11.4+/-0.7 Æ a high prevalence (23.3 %) of unknown causes of CRI, which could be due to late to 12.8+/-1.3 g/dl (p=0.02 Fig 1.) Mean cell volume increased 87.7+/-3.4 to 90.1+/-3.7 fl (p=0.01) and mean cell Hb decreased 33.4+/-0.2 to 32.9+/-0.4 pg (p=0.03). Absolute and referral: in 74% of cases diagnosis of CRI was made when CrCl was < 30 ml/min/1.73; percentage reticulocyte count remained unchanged. There was no change in iron indices: Æ an underdiagnosis of VUR (2.6% vs 24% of Italkid) and a higher prevalence of Ferritin 55.1+/-31.3 to 97.3+/-46.5 ng/ml (p=0.3), Iron 18.9+/-6.9 to 18.1+/-4.2 umol/l neurogenic bladder (13.8% vs 3.7%), lupus nephritis (3.4 % vs 1%) and glomerulopathies (p=0.7), transferrin 1.9+/-1.6 to 2.0+/-0.1 g/l (p=1.0), transferrin saturation 35.7+/-8.1 to (34.5 % vs 6.8%). 40.3+/-18.0 % (p=0.5). These data underlie the need for diagnostic support in the Nicaraguan peripheral hospitals, CONCLUSION to allow for an earlier diagnosis and treatment of CRI and urinary tract infections and IV iron improved Hb levels in paediatric CRF and PD patients who were not receiving malformations. The high prevalence of neurogenic bladder and glomerulopathies suggests EPO. This strategy may delay the need for EPO treatment and deserves further evaluation. the primary and secondary treatment of these diseases be improved. The impact of the project in reducing mortality due to CRI will be evaluated over the next 2 years through an expanded database. Pediatr Nephrol (2006) 21:1493–1635 1603

COD. PP 325 COD. PP 326 Psychiatric disorders in a sample of Egyptian children with chronic Behavioral profile in a sample of Egyptian children with chronic renal renal failure failure M Amr, A Bakr, A Sarhan, A Hammad, M Ragab, A El-Refaey, A El-Mogy A Bakr,M Amr, A Sarhan, A Hammad, M Ragab, A El-Refaey, A El-Mogy Mansoura University Children`s Hospital , Pediatric Nephrology Unit, Mansoura University Mansoura University Children`s Hospital , Mansoura University Children`s Hospital, Children`s Hospital , 35516 Mansoura , Egypt Gumhoria street , 35516 Mansoura , Egypt

Psychiatric assessment was done according to DSM-IV TR criteria in 19 children with To identity the presence of behavioral problems in children with chronic renal failure (CRF) predialysis chronic renal failure (CRF) and 19 children with end stage renal failure on 19 patients in predialysis stage (group I) and 19 patients on regular hemodialysis (group II) regular hemodialysis. The prevalence rate of psychiatric disorders in all the studied patients using child behavior check list (CBCL). No significant differences were noticed in was 52.6%. Adjustment disorders were the most common disorders (18.4%) followed by externalizing CBCL score between the two groups while group II patients had significantly mode disorders (10.4%) and neurocognetive disorders (7.9%). Anxiety and elimination higher internalizing score compared with group I. However 36.8% of group II and 26.3% of disorders were reported in 5.3% and 2.6% respectively. The disorders were more prevalent group I patients had scores in the clinical range of the externalizing CBCL score. in dialysis (68.4%) than in predialysis patients (36.8%). However the presence of Concerning the internalizing scores, parents of group II patients reported problems of psychiatric disorders were not significantly associated with age, sex, severity of anemia, sornatic complains in 47.4%, withdrawn in 36.8%, and anxious/depressed in 31.6% while in duration of CRF or the efficiency or the duration of hemodialysis. In conclusion, psychiatric group I these complains were noticed in 42.1%, 15.8% and 5.3% respectively. Regarding disorders were prevalent in our patients especially those on hemodialysis. This array of the externalizing scores delinquent and aggressive behaviors were more prevalent in group disorders was more likely explained by the difficulties encountered in living with CRF than II compared with group I patients (15.8% vs 5.3% respectively). No significant correlations by demographic or physical factors. were found between any of CBCL scores and either of age, sex, severity of anemia, duration of CRF or the efficiency or the duration of hemodialysis. In conclusion behavioral problems were more common in CRF children on hemodialysis than in those in the predialysis stage. These children tend to display more internalizing problems in a trial to adapt to stressful life events inherent in living with CRF.

COD. PP 327 COD. PP 328 Angiotensin II receptor blockers as add-on renoprotection in children PRELIMINARY ASSESSMENT OF HEART FUNCTION IN with chronic renal disease treated with ACE inhibitors. CHRONICALLY DIALYSED CHILDREN M Litwin, R Grenda, J Sladowska, J Antoniewicz Droýdý D1, Rudziñski A 2, Kordon Z 2, Dro ýdý M 4, Zachwieja K 3, Miklaszewska M 3, The Children`s Memorial Health Institute , Dept. of Nephrology, Kidney Transplantation Dziedzic A 5, Pietrzyk JA 1 Dept. of Pediatric Nephrology1, Dept. of Pediatric and Arterial Hypertension; Al. Dzieci Polskich 20 , 04-730 Warsaw , Poland Cardiology2, Dialysis Unit3, Dept. of Nephrology4, Cracow, Children’s Hospital 5, Limanowa The standard renoprotection is based on inhibition of renin-angiotensin-system by Dept. of Pediatric Nephrology , 265 Wielicka Str. , 30-663 Cracow , Poland angiotensin convertase inhibitors (ACEi) or angiotensin II receptor 1 blockers (AT1B). The aim of our study was to analyze effects of combined therapy after addition of AT1B to The main aim of the study was an echocardiographic (ECHO) assessment of selected ACEi based renoprotection in children with CKD stage 2-4. Patients and methods: 11 cardiac parameters in dialysed children. Methodology: 16 chronically dialysed (6 HD, 10 children, aged 10.8 yrs (0.5 - 18 yrs) with mean glomerular filtration rate (GFR) 50 ±45 PD) children participated in the study (10 M, 6 F), aged 5 – 18,5 yrs (x = 12,2 ± 3.8 yrs). ml/min/1.73m2. In 4 pts the primary renal disease was hemolytic uremic syndrome, in 3 Echocardiography examinations were carried out with HP 5500 device and S4 ultrasound congenital nephrotic syndrome (CNS), in 3 reflux nephropathy, in 1 acute cortical necrosis. probe of variable frequency. Diastolic and systolic LV dimension, ejection fraction (EF) and All pts were treated with complex hypotensive ACEi- based therapy. AT1B losartan was LV mass index (LVMI) were evaluated. By means of pulsating Doppler method mitral flow added in mean dose 0.7 mg/kg/day. Change in GFR, proteinuria and blood pressure at two peak E and A velocity and isovolumetric relaxation time (IRT) were assessed. Results: On 12 months intervals before and after adding AT1B were compared. Results: during 12 mts the basis of ECHO examinations 3 groups were singled out: A (n=3) of normal heart preceding AT1B therapy there was no change in blood pressure and proteinuria and GF R function, B (n=3) of impaired systolic and diastolic heart function and C (n=10) of normal declined in 9 of 11 pts. At 12-th month of add-on therapy with AT1B there was significant systolic and impaired diastolic heart function. In group of children with severe cardiac decrease in both absolute and indexed blood pressure values. Proteinuria decreased in 8 pts, lesion (B group) a higher LV mass (A vs B vs C: 74,7 vs 119,9 vs 73,5 g/m) and did not change in 1 and increased in 2 including one with CNS. GFR stabilized or increased statistically significant lower ejection fraction (68,1 vs. 33,7 vs. 65,9 %) were ascertained. in 8 pts and decreased in 3 pts with CNS. In 7 of 11 pts there was significant, but not These children were anuric (996 vs. 0 vs. 1112 ml/d), their systolic (102,1 vs. 118,4 vs. threatening increase in serum potassium. Conclusion: add-on renoprotection with AT1B 117,9) and diastolic (64,4 vs. 84,8 vs. 77,9) blood pressure were significantly higher, so was added to ACEi is safe and significantly improves renoprotective effects of ACEi treatment the number or hipotensive medications (0,33 vs. 1,72 vs. 1,44). Conclusions: The great in children with progressive nephropathies, including pts with advanced CKD. However, no majority of chronically dialysed children demonstrates an impairment of cardiac function significant effect was seen in pts with CNS. mainly of diastolic parameters. Anuria and hypertension stand for a significant risk factor of cardiac lesion. 1604 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 329 COD. PP 330 NEUROPHYSIOLOGIC EVALUATION OF PERIPHERAL NERVE CONGENITALAND GENETIC RELATED CAUSES OF END- FUNCTION IN UREMIC EGYPTIAN CHILDREN STAGE RENAL DISEASE – DATA FROM POLISH REGISTRY OF M Ragab * presenting author M Al-Haggar M Al-Aiouty S Yehia RENAL REPLACEMENT THERAPY IN CHILDREN 2000-2004. , Tadawi General Hospital, PO box 3823 , 31481 Dammam , Saudi Arabia I Zagozdzon ( presenting author), A Zurowska, I Balasz, A Boguszewska, S Prokurat, J Pietrzyk, D Drozdz, M Szczepanska, E Stefaniak, A Jander, D Roszkowska-Blaim, H Information concerning clinical and sub-clinical peripheral neuropathy in uremic children is Ziolkowska, I Makulska, B Kollataj, T Jarmolinski, G Siten, R Stankiewicz, R Wiercinski still scarce. We aimed to evaluate role of neurophysiologic testing for detection o f Medical University of Gdansk , Department Paediatric Nephrology , 80-211 Gdansk , peripheral nerve dysfunction in asymptomatic uremic Egyptian children. A cohort of 81 Poland uremic children were enrolled from Pediatric Nephrology Unit in Mansoura University Children`s Hospital; it comprised 39 cases on conservative therapy; CG (27 males and 12 One of the objectives of Polish Registry of Renal Replacement Therapy in Children females, with mean age 9.8±3.3 years) and 42 cases under regular hemodialysis for at least established on 31st Dec. 2000 was to collect complete data on etiology of end stage renal 6 months; HG (27 males and 15 females, with mean age 11.8±1.6 years). A third group o f disease (ESRD) in polish children. twenty healthy children were taken as control (12 males, and 8 females, with mean age Material and Methods: Data on 469 patients (251 boys, 218 girls) aged 0-22 years treated 9.9±2.4 years). Nerve conduction studies including motor and sensory functions were done with renal replacement therapy (RRT) at 13 pediatric dialysis units in Poland from 2000 to successfully in most cases; data were analyzed using SPSS version 10.0.Different 2004 were analyzed. The mean age at start of dialysis was 10 years and 3 months. Renal proportions of abnormal motor and sensory conduction studies were reported in both diseases were defined according to EDTA coding system. Data is presented for the whole patients` groups with reference to pediatric ranges built-in Sierra II software. Comparing group, in 5-year age groups and separately for sexes. these observations to controls, motor peroneal and median conduction velocities as well as Results. Congenital and genetic renal diseases were the cause of ESRF in 56% of the polish sensory ulnar conduction velocity were significantly delayed in HG (38.46±4.49 Vs population of children and adolescents on RRT. 39% of causes were acquired diseases, 5% 48.33±3.35 for peroneal, 50.68±10.87 Vs 57.22±7.13 for median and 32.82±9.8 Vs remained unidentified. Congenital and genetic causes dominated in children < 5 years of 52.08±20.12 for ulnar nerve). However in CG antidromic sensory median conduction was age (71%). They accounted for 49%, 61% and 45% of causes in the consecutive 5-year age the only significant abnormality detected (41.13±9.63 Vs 53.89±12.32). F wave latencies in groups. The most numerous group of congenital diseases leading to ESRF were uropathies CG were almost normal but in HG they were moderately affected compared to controls.We (29%). In boys the most frequent uropathy was obstructive uropathy (25%), the majority concluded that sensory dysfunction could be early detected in asymptomatic uremic caused by posterior urethral valves. In girls the most frequent uropathies were reflux children by neurophysiologic testing. Further prospective studies should be warranted to nephropathy (10%) and nephropathy secondary to neurogenic bladder (9%).Uropathies evaluate sequential electrophysiological changes in response to hemodialysis. were followed by renal hypo-dysplasia without urinary tract anomalies (11%) and cystic diseases (10%). Results Conclusions: Congenital kidney anomalies and genetic diseases are the leading cause of end- stage renal disease in children up to 15 years of age.

COD. PP 331 COD. PP 332 Expression of granzyme B in cytotoxic T lymphocytes in children on A MODEL OF INTERNATIONAL COOPERATION IN PEDIATRIC dialysis - a pilot study NEPHROLOGY M Zaniew, J Zachwieja, M Lewandowska-Stachowiak, A Warz ywoda G Marra, A Edefonti, SM Vigano, G Selvaggio, M Sandova*l, Y Silva Galan* and F Sereni , Department of Pediatric Nephrology, Szpitalna 27/33 street , 60-572 Poznañ , Poland Pediatric Renal Units of Clinica Pediatrica De Marchi, Fondazione O.M. Policlinico, Mangiagalli e Regina Elena, Milano, Italy, and Hospital Manuel de Jesus Rivera - La End-stage renal disease (ESRD) patients are prone to infections that result from an impaired Mascota, Managua, Nicaragua* function of various cell types. Little is known, however, of cytotoxic T lymphocyte (CTL) Pediatric Renal Units of Clinica Pediatrica De Marchi, Fondazione O.M. Policlinico, activity, which is critical for defence against viruses and tumor cells. Thus, this study was Mangiagalli e Regina Elena , Via Commenda 9 , 20122 Milan , Italy conducted to establish CTL function by analyzing the expression of granzyme B (GrB) in children treated with dialysis. We studied 28 children (median age: 15 yrs) on chronic A project of international cooperation was started in 1996 with the aim of developing dialysis. 20 had no infection and were treated with hemodialysis (HD; n=8) and peritoneal pediatric nephrology in Nicaragua, It was financed initially by the Associazione Bambino dialysis (PD; n=12). 8 chronically HBV/HCV-infected children formed separate group. GrB Nefropatico (ABN), then by a joint venture of ABN, the Regional Government of expression was measured by intracellular staining (anti-GrB PE) in CD8+ and CD8+/CD28- Lombardy and a Nicaraguan charity association, to reach the present budget of about T cells by flow cytometry. This study demonstrated a tendency for a reduced intracellula r 250.000, 00 Euros/year. expression of GrB in HD patients compared to controls in CD8+ (13.50±8.75 vs. The project started with training in Milan 3 pediatric nephrologists, 2 pediatric urologists 19.35±12.54, NS) and CD8+/CD28- cells (17.57±16.85 vs. 25.20±16.59, p=0.075). There and 1 dialysis nurse, and the formalization of basic protocols. were no differences between PD patients and controls. However, in children on PD we The remodeling of the “La Mascota” Nephrology Unit was the second step, followed by the observed a higher proportion of CD8+/GrB+ cells (29.17±26.00 vs. 13.50±8.75, p=0.075) supply of basic and then more advanced diagnostic, instrumental (including renal biopsy) compared to those on HD. The analysis in children with chronic HBV/HCV infection and therapeutic tools. displayed evidence of increased percentage of GrB-positive CD8+ cells compared to As a third step, dialysis and living donor transplant programs were established in 2005. controls (p=0.043). Furthermore, we found a negative correlation between the number of T Finally, the project was extended to 5 peripheral hospitals, supplied whith basic diagnostic cells expressing GrB and BUN in children with ESRD (CD8+: r=-0.52, p=0.017; and treatment tools and protocols, and connected on-line with “La Mascota” for clinical CD8+/CD28-: r=-0.61, p=0.003). Conclusions: Children with chronic hepatitis on dialysis advice of complicated cases. The Managua and Milan units were also connected. show higher expression of GrB in CTL. Further longitudinal studies are required to In the meantime, a Nicaraguan database was implemented (about 1600 patients till now), determine CTL activity in dialyzed patients. which is the premise of an ongoing Registry of Chronic Renal Insufficiency. The clinical and organizational impact of our cooperation program has recently prompted the Nicaraguan Ministry of Health to finance the expenses of pediatric renal transplantation, starting from 2007. In conclusion, we propose a model to implement a comprehensive pediatric clinical assistance in a developing country, which includes a highly specialized hospital unit together whith a rather extensive territorial diagnostic and assistance program. Pediatr Nephrol (2006) 21:1493–1635 1605

COD. PP 333 COD. PP 334 LOW HAIR SELENIUM AND PLASMA GLUTATHIONE Use of Bioelectrical Impedance Analysis (BIA) to evaluate nutritional PEROXIDASE IN CHILDREN WITH CHRONIC RENAL FAILURE assessment and growth in children with Chronic Renal Failure (CRF). E Ortaç1, O Ozkaya 1, R Saraymen 2, N Y›ld›z 3, A Bedir 4, N Buyan5, K Bek1 , A A Pota, M L Sirico, A Pota, A Fella, G Malgeri, G Raddi, C Pecoraro Okuyucu4, K Baysal 6 1 Ondokuz May›s University Faculty of Medicine, Dept.of Pediatric Santobono Children`s Ospital , Department of Nephourology, Via M. Fiore 6 , 80129 Nephrology, Samsun,Türkiye 2 Dept.of Biochemistry, Erciyes University Faculty of Naples , Italy Medicine , Kayseri, Türkiye 3 Dept of Pediatrics, Social Security Göztepe Hospital, Ýstanbul, Türkiye 4 Dept of Biochemistry, Ondokuz May›s University, Faculty of Medicine, INTRODUCTION: Children with CRF are at risk of protein energy malnutrition and Samsun, Türkiye 5 Dept.of Pediatric Nephrology, Gazi University, Faculty of Medicine, growth impairment. Abnormalities in the distribution of fat and lean tissue compromise the Ankara, Türkiye 6 Dept of Pediatric Cardiology, Ondokuz May›s University, Faculty of interpretation of the common anthropometric measures to evaluate nutritional status. BIA is Medicine, Samsun, Türkiye used to estimate the volumes of body fluid compartments and some of the equations Ondokuz may›s University Faculty of Medicine , Department of Pediatric Nephrology , developed by this technique are used to estimate the Fat Free Mass(FFM), the Body Cell 55139 Samsun , Turkey Mass(BCM), the Muscle Mass(MM), the Body Cell Mass Index(BCMI) and the Bia Vector (BIVA). Aim of this study was to evaluate the association between BIA equations and Background/Aim:Selenium (Se) is a trace element which incorporates into the height, BMI and SDS for growth velocity in the follow-up of the children with CRF. selenoenzyme glutathione peroxidase (GSH-Px). There are conflicting results regarding the METHODS AND STATISTICAL ANALYSIS: We studied 70 children with CRF Se levels and activity of GSH-Px in adult uremic patients. The aim of this study was to (M/F,50/20; age 6.8±5.0years;Creatinine clearance 48±28ml/min) with different determine (I) the hair Se status (ii) possible relation between hair Se status and the nephropathies, and a follow-up of 12to96months. At each visit we measured height, BMI, antioxidant enzyme, GSH-Px (iii) the influence of different treatment procedures on hair Se SDS for growth velocity and the BIA measurements (19.4±10.6 status and GSH-Px activity in children with CRI , treated conservatively and those on HD determinations/child).Statistical analysis included ANOVA, stepwise linear regression and and on CAPD . Pearson correlation coefficient analysis as appropriate. RESULTS:The variation ( ? ) of BMI Methods: Ninety-three patients including 32 patients with CRI, treated conservatively, 42 every 6 months of follow-up is associated with ? FFM, ? BCM, ? MM, ? BCMI and ? BIVA PD patients and 19 HD patients and 34 healthy children were enrolled into the study. Hair (p<0.001). The ? of SDS for growth velocity every 6 months of follow-up is associated Se level was measured by atomic absorption spectrophotometer method. Plasma GSH-Px with ? FFM, ? BCM, ? MM, ? BCMI and ? BIVA (p<0.001). CONCLUSION: The strong activity was determined using a Randox test combination (RANSEL). association between BIA derived equations and BMI and between BIA derived equations Results: Hair Se levels were significantly lower in CRI (527.75 ± 261.08 ng/g), CAPD and SDS for growth velocity seems to indicate that the Bioelectrical Impedance Analysis is (547.25 ± 288.97 ng/g) and HD (485.42 ± 256.27 ng/g) groups when compared to control an easy, low cost and reliable method to evaluate the nutritional assessment and the growth group (1025.57 ± 345.80 ng/g) (p=0.001, p=0.001, p=0.001, respectively) There was no in children with CRF. statistically significant difference in hair Se levels among three groups. Plasma GSH-Px activity was significantly lower in CRI (30.43 ± 16.14 U/L), CAPD (18.93 ± 8.01 U/L) and HD (22.98 ± 11.05 U/L) groups when compared to control group (58.85 ± 16.89 U/L) (p=0.001, p=0.001, p=0.001, respectively). Conclusion: These results revealed decreased hair Se level and impaired antioxidative capacity in children with CRI, on CAPD and, HD. Whether Se supplements can prevent the oxidative stres in these patients should be further investigated with more detailed studies based on the present one.

COD. PP 335 COD. PP 336 Heart imaging by body surface mapping in children with chronic renal The CRF onset timing plays a more important role in the growth failure (CRF)- preliminary results velocity and nutritional status of children than the hGH treatment. D Polak-Jonkisz D Zwolinska K Laszki-Szczàchor W Pilecki M Sobieszczanska R Bednorz A Pota, M L Sirico, A Pota, A Fella, R Indaco, L Marzano, C Pecoraro K Musial Santobono Children`s Hospital , Department of Nephrourology, Via M. Fiore 6 , 80129 Medical University, ul.M.Sklodowskiej 50/52 , Department of Pediatric Nephrology , 50- Naples , Italy 369 Wroclaw , Poland The progressive loss of renal function in children with CRF leads to metabolic Cardiovascular complications are a significant problem in CRF patients. Among factors abnormalities and has a negative influence on nutritional state and growth. Children who destroying heart muscle there are hypertension, anemia, hypervolemia, uremic toxins and have a negative SDS for height or for height velocity for age, are candidate to receive electrolyte disturbances. They may lead to arrythmias and other abnormalities, found recombinant hGH treatment. The aim of our study is to evaluate the factors influencing especially in patients on hemodialysis. Body surface mapping is noninvasive method growth in children with CRF. We studied 70 children with CRF (M/F,50/20; Age, revealing early changes within the human heart. Isointegral map shows net changes in the 6.8±5.0years; Creatinine Clearance 48±28ml/min) with different nephropaties and with a exact period of time. The aim of the study was a preliminary analysis of changes in cardiac follow-up of 12 to 96months. We evaluated at each visit height, weight, the principal image examined by body surface mapping in children with CRF. The study was performe d progression and nutrition measurements and the therapies. We selected two groups on 18 CRF patients (mean age 16.3years) divided into several sugroups ( gr.IA-5 patients according to the mean values of SDS Growth Velocity(SDSGV) (gr.A, n=45pts with a on hemodialysis; gr.IB- 4 patients on peritoneal dialysis; gr.II - 9 CRF patients on positive and gr.B, n=25pts with a negative mean value of SDSGV during the follow-up).We conservative treatment). The control group consisted of 12 healthy children with normal performed ANOVA for continous and chi-square test for ordinal variables. Our data show electrocardiography. Kidney function ( serum urea, creatinine), hematocrit and classical that there was a difference between groups for CRF onset timing(p<0.05) and no difference electrocardiography were performed in all patients. The japanes system HPM 7100 was for Height and BMI SDS, gender and type of nephropaty at the beginning of follow-up. used to register electric field of heart ( 87 electrodes on surface: 59 electrodes in the front During the follow-up serum levels of Urea, Total Protein, Albumin and Albumin/Globulin and 28 electrodes on back). Map isointegral was created on base these records. In patients were more elevated in gr.A than in gr.B(p<0.05). There was no difference between groups were analysed area QRS and QRS-T on their isointegral maps. The obtained results are for loss of GFR (ml/year), for Hemoglobin and no difference in the percentage of patients shown in the table. Conclusions: 1. Body surface mapping describes precisely changes in recieving hGH (gr.A vs gr.B, 27%vs28%) and Erythropoietin (47%vs56%) treatment. Ou r distribution of integral values in different regions of heart muscle. 2. In patients on study suggests that the influence of CRF onset timing on the growth velocity and nutritional hemodialysis the isointegral maps indicate occurrence of disturbance block in left branch - status in children seems to be greater than hGH treatment. Hisa, at lack of deviation in classic electrocardiography. 1606 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 337 COD. PP 338 Prevalence of Complications in Children with Chronic Kidney Disease Should K/DOQI guidelines for anemia be used in children? according to K/DOQI G Filler, K Mylrea, J Feber, H Wong H Wong, K Mylrea, F Feber, G Fille r Children`s Hospital of Eastern Ontario , 401 Smyth Road , K1H8L1 Ottawa , Ontario Children`s Hospital of Eastern Ontario , 401 Smyth Road , K1H8L1 Ottawa , Ontario Canada Canada Publication of the National Kidney Foundation’s Dialysis Outcomes Quality Initiative Background: The Kidney Disease Outcome and Quality Initiative (K/DOQI) Group Clinical Practice Guidelines (K/DOQI guidelines) influenced the clinical practice also in recommended guidelines for the monitoring and treatment of chronic kidney disease (CKD) children, although the support for the anemia guidelines remains scarce. in 2002. These recommendations were based on the prevalence of known complications as Hemoglobin (Hgb) and hematocrit (Hkt) in children are age- and gender-specific. In a seen in adults. In children, the exact prevalence of these complications is not known. We cross-sectional study, we compared the K/DOQI anemia definitions (Hgb<110 g/L and therefore conducted a study to examine the current prevalence of complications of CKD in Hkt<0.33) with age-and gender-specific reference intervals in 351 children with CKD stage children using the K/DOQI recommendations. I-V. GFR was determined by Cystatin C GFR. Methods: Cross sectional survey of 366 patients with CKD in a single pediatric nephrology The Cystatin C-derived GFRs were 122±36 mL/min/1.73 m2 in patients with stage I CKD center. Clinical information was collected from the patient charts. Cystatin C was used as a (n=196), 76±8 mL/min/1.73 m2 in patients with stage II (n=104), 45±9 mL/min/1.73 m2 in measure of renal function. patients with stage III (n=36), and 22±5 mL/min/1.73 m2 in patients with stage IV and V Results: The most prevalent cause of kidney disease was uropathy (43.87%). Glomerular CKD (n=15). 59 patients were on iron therapy, 15 in stage I CKD (7.7%), 13 in stage II disease accounted for 27%. The overall prevalence of complications were as follows: CKD (12.5%), 18 in stage III (50%), and 13 in stage IV or V (86.7%). 9 children with stage hypertension 61.7%, anemia 36.6%, proteinuria 11.5%, metabolic bone disease 16.9% and II CKD (8.7%), 9 with stage III (25%), and 13 with stage IV or V (86.7%) received growth failure 11.5%. The prevalence of all complications increased with worsening stage Darbepoitin therapy. For Hgb, a total of 90 patients fitted the age- and gender derived of kidney disease (all p values significant). Metabolic bone disease and anemia occurred criteria, significantly lower than the 54 identified by the K/DOQI guidelines (p=0.0010). more frequently and at a higher glomerular filtration rate than in adults. In contrast, the Similarly, for Hkt, a total of 78 patients fitted the age- and gender derived criteria, overall prevalence of hypertension was lower than in adults. significantly lower than the 56 identified by the KDOQI guidelines (p=0.0435). There was a Conclusions: This study supports the use of the K/DOQI definition and staging criteria for significant correlation between the GFR and the Hgb z-score (p= 0.0068) or the Hkt (p= CKD in children. However, the prevalence of complications is markedly different from 0.0128), but not for the absolute Hgb. adult CKD patients. There was poor agreement between the conventional and the K/DOQI anemia definitions. This warrants additional studies on larger patient cohorts.

COD. PP 339 COD. PP 340 Behavioral profile in a sample of Egyptian children with chronic renal A case of severe anemia due to anti-erythropoeitin antibodies in chronic failure renal failure A Bakr, M Amr, A Sarhan, A Hammad, M Ra gab, A El-Refaey*, A El-Mogy* L Stapenhorst 1, J Gross 2, U Bangen 1, B B Beck 1, C Licht 1, J Devange 1, D Michalk 1, Mansoura University Children`s Hospital , Mansoura University Children`s Hospital, B Hoppe 1 1 Division of Pediatric Nephrology, University Children’s Hospital 2 Pediatric Nephrology Unit Gumohoria street , 35516 Mansoura , Egypt Molekularbiolog. Forschungslabor, Charité, Campus Virchow Klinikum, Berlin. Presenting author: L Stapenhorst To identity the presence of behavioral problems in children with chronic renal failure (CRF) Childrens Hospital University of Cologne , Josef-Stelzmannstr. 9 , 50931 Cologne , 19 patients in predialysis stage (group I) and 19 patients on regular hemodialysis (group II) Germany using child behavior check list (CBCL). No significant differences were noticed in externalizing CBCL score between the two groups while group II patients had significantly Recombinant human erythropoeitin (rHuEPO) is a major tool in the treatment of patients higher internalizing score compared with group I. However 36.8% of group II and 26.3% of with anemia caused by chronic renal failure (CRF). The development of anti-erythropoeitin group I patients had scores in the clinical range of the externalizing CBCL score. (anti-EPO) antibodies following treatment with rHuEPO has been observed in a small, but Concerning the internalizing scores, parents of group II patients reported problems of increasing number of patients. This causes pure red cell aplasia and requires at least sornatic complains in 47.4%, withdrawn in 36.8%, and anxious/depressed in 31.6% while in withdrawal of treatment. We report severe anemia due to anti-EPO antibodies in a 6 year- group I these complains were noticed in 42.1%, 15.8% and 5.3% respectively. Regarding old boy with cystic fibrosis, associated hepatic cirrhosis and end stage renal failure due to the externalizing scores delinquent and aggressive behaviors were more prevalent in group obstructive uropathy. rHuEPO therapy was started in a dosage of 130 i.U./kg body weight II compared with group I patients (15.8% vs 5.3% respectively). No significant correlations s.c. weekly, primarily with a good response. With decreasing kidney function anemia were found between any of CBCL scores and either of age, sex, severity of anemia, deteriorated and consecutively the rHuEPO dosage was stepwise increased up to 250 duration of CRF or the efficiency or the duration of hemodialysis. In conclusion behavioral i.U./kg weekly. In spite of optimized iron, folic acid, vitamine C and B12 supplementation problems were more common in CRF children on hemodialysis than in those in the he became refractory to treatment and hemoglobin decreased to a minimum of 4.8 g/dl, predialysis stage. These children tend to display more internalizing problems in a trial to hence blood transfusion was necessary. A bone marrow aspirate showed normal erythroid adapt to stressful life events inherent in living with CRF. precursors, no red cell maturation arrest and normal numbers of white cell and platelet precursors. We then identified circulating anti-erythropoietin antibodies with a maximum titer of 284.7 ng/ml as main culprit for the anemia. rHuEPO treatment was stopped, the anti- EPO antibody titer fell to 113 ng/ml after 6 weeks and to 30.2 ng/ml after 3 months without specific immunsuppressive therapy. Hemoglobin levels recovered and are currently stable with values around 9 mg/dl without rHuEPO treatment. In conclusion, anti-EPO antibodies have to be kept in mind in patients with treatment refractory anemia. Pediatr Nephrol (2006) 21:1493–1635 1607

COD. PP 341 COD. PP 342 FREQUENCY OF DYSPEPSIA, GASTRODUODENAL LESIONS Determinants of vascular changes in children with chronic renal AND H.PYLORI INFECTION IN DIALYSIS PATIENTS insufficiency F Ozcay*, E Baskin**, E Melek**, O Canan*, N Cengiz**,PI Agras**, H Sakalli**, Y H. Ziolkowska 1, M. Brzewski 2, M. Roszkowska-Blaim 1 1. Department of Pediatrics and Uslu** Depts of Pediatric Gastroenterology* and Nephrology**, Baskent University, Nephrology Medical University of Warsaw 2. Department of Pediatric Radiology Medical Ankara, TURKEY University of Warsaw Baskent University hospital , Dept of Ped Nephrology 6.cadde 72/3 , 06490 Ankara , Department of Pediatrics and Nephrology Medical University of Warsaw , Marszalkowska Turkey 24 , 00-576 Warsaw , Poland Poland

Dyspepsia and gastroduodenal lesions are more frequent in adult patients with chronic renal The aim of the study was to determine the risk factors of changes in arterial wall in children failure (CRF) than the normal population. The data related to GI findings in children with with CRI. CRF in the literature are limited. The aim of this study is to investigate the dyspeptic 60 patients, aged 13.9±4.4 years, 32 with chronic renal failure (CRF), 28 with end-stage symptoms, endoscopic findings and the frequency of Hp infection in dialysis patients. A renal disease (ESRD) were examined. Examinations of intima-media thickness (IMT) of total of 29 patients on dialysis were included in the study. The patients underwent upper GI carotid arteries were performed by one radiologist. In children were estimated: age, duration endoscopy. Urease test was performed in antral biopsy specimens in all patients. of dialysis therapy, doses of alphacalcidol and CaCO3, serum level of total cholesterol There were 18 male and 11 female patients with a mean age of 14.3 3.4 (8-20) years. (TC), HDL and LDL cholesterol, triglycerides (TG), calcium (sCa), phosphorus (sP), Twelve out of 29 patients were on PD, while 17 patients were on HD. The frequency o f parathormone total (PTH), CAP and CIP fragments, osteocalcine (OC), osteoprotegerin dyspepsia was 38% in all patients. Upper GI endoscopic examination revelead abnormal (OPG), fetuin A and alkaline phosphatase (AP). Calcium-phosphorus products (CaxP), findings in 75% of the patients in both groups. PD and HD groups were similar in respect to CAP/CIP ratio were calculated. According to IMT in healthy children (Jourdan et al. J upper GI endoscopic findings (p>0.05). Urease test in antral biopsy specimens revealed Hp Hyper 2005) patients were divided into two groups: I - with normal arteries (n=23), II - infection in 10 (58.8%) of patients in HD patients, while none of the PD patients had a arterial changes (n=37). positive test result. There were no significant relation between the dyspeptic symptoms and Results. Hypertension in 30.4% group I, and 48% group II was observed (NS). In group I the presence of Hp infection. the length of dialysis therapy was shorter (28±18 vs 61±39 months) and fetuin A level was As a result Hp infections were found to be more frequent in HD patients. Dyspeptic higher (114±12 vs 101±14 ng/ml) than in group II. In group I the tendencies (p = 0.06) to complaints are common in children with CRF. The frequency of these complaints is not higher CAP/CIP ratio (1.7±1.6 vs 1.4±1.7) and lower age (12.6±4.3 vs 14.7±4 years) was related to the type of dialysis and the presence of Hp infections. observed. The other parameters were not significantly different between group I and II. Conclusion: The changes in arterial wall in children with CRF are mainly related to length of time on dialysis therapy and low fetuin A level. The age and CAP/CIP ratio may be also significant for these changes.

COD. PP 343 COD. PP 344 Early detection and treatment of Membranoproliferative TACROLIMUS- A NEW THERAPY FOR STEROID RESISTANT glomerulonephritis(MPGN) type I in Children NEPHROTIC SYNDROME IN CHILDREN Sung-Do Kim, Byoung-Soo Cho S Gulati,A Kumar,Sharma RK,M Jain2, Prasad N and A Gupta Department of Nephrology East West Kidney Diseases Research Institute , Dept. of Pediatric Nephrology, Hoegi-dong, and Pathology2 ,Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow Dongdaemun-gu , 130-702 Seoul , South Korea India Sanjay Gandhi Post Graduate Institute of Medical Sciences , Rae Bareli rd , 226014 MPGN is one of the common chronic kidney diseases with poor prognosis. Mass school Lucknow , Uttar Pradesh India urinalysis screening test have been performed by law since 1998 in Korea. We compared the prognosis of MPGN between asymptomatic MPGN, which is detected by school This study was conducted evaluate the safety and efficacy of Tacrolimus in children with screening and symptomatic MPGN. We analyzed the characteristics and prognosis of the 15 SRNS.The study group comprised of 10 consecutive children with SNRS. All of them were patients with MPGN type I who admitted after 1998. Follow-up was continued for 4.5 years treated with 8 weeks course of standard prednisone therapy before being labelled as SRNS. (from 2 to 7 years). Among 15 patients, 7 patients were diagnosed through school urinary Tacrolimus was given at 0.15 – 2.0 mg/kg/day divided in two doses. These patients were screening, 8 patients presented with nephritic syndrome, acute renal failure or gross followed-up every 2 weekly initially for the first month, followed by monthly visits. Urine hematuria at diagnosis. In the school screening test, 4 patients presented proteinuria with spot protein creatinine estimation was done at each visit Besides blood glucose, serum hematuria, 1 patient did isolated proteinuria, and 2 patients did isolated hematuria. These creatinine, urea, electrolytes, albumin, and complete blood count were done once a month. last 2 patients showed also proteinuria during follow-up that was indicated for renal biopsy. The mean age of onset was 7.30 + 5.2 yrs and. there were 8 boys and 2 girls. Of the 10 Among them, only 2 patients showed hypocomplementemia initially. After pulse children, 5 had MCD, 3 had FSGS and another 2 had MesPGN on histopathology. Of these methylprednisolone, 4 patients had remission (57%) without proteinuria and hematuria, and 8 had primary steroid resistance, while 2 had secondary steroid resistance. Tacrolimus no patient has showed renal insufficiency. At diagnosis, 6 patients showed nephrotic resulted in complete remission in 7 of the 10 children, 1 had a partial remission and another syndrome, 1 patient showed gross hematuria with proteinuria and 1 patient was acute renal 2 children continued to have proteinuria.. None of the children developed hyperglycemia. failure with gross hematuria. Among them, 4 patients showed hypocomplementemia The mean urine spot protein/ creatinine ratios were significantly lower (17.7 +29.6 vs initially. And 2 patients had remission (25%), 1 patient required hemodialysis and 1 patient 1+1.24, p= 0.047) and the mean serum albumin levels were significantly greater ( 2.38+0.57 presented renal insufficiency. Although further long-term study is needed to confirm, vs 3+0.77, p=0.001) following Tacrolimus therapy as compared to those prior to therapy. however, our studies showed early detection by school screening and early massive We conclude that Tacrolimus is a useful therapeutic alternative in children with SRNS who methylprednisolone pulse therapy plus urokinase therapy might be helpful therapeutic are unresponsive to Cyclophosphamide and Cyclosporine regimen in patients with MPGN type I 1608 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 345 COD. PP 346 MYCOPHENOLATE MOFETIL IN THE TREATMENT OF Clinical and pathohistological characteristics of biopsy-proven renal STEROID-RESISTANT NEPHROTIC SYNDROME IN CHILDREN diseases in children in Croatia L Prikhodina*, V Dlin, O Turpitko, O Katysheva, T Lepaeva, E Agapov, T Nikishina, M D Batiniã1, M Šãukanec-Špoljar4, D Miloševiã1, M Šubat-Dežuloviã2, M Saraga3, J Ignatova Ðelmiš6, Z Puretiã5, A Cvitkoviã-Kuzmiã7, Lj Nižiã1, K Vrljièak1, M Matkoviã1, H Institute of Pediatrics & Children Surgery , Nephrology Department , 125412 Moscow , Kniewald1, I Borojeviã1, D Batiniã1, L Grkoviã1, S Flajšman2, Ð Košuljandiã-Vukiã3, M Russia Ãoriã4, M Glavina-Dundov3, G Ðorðeviã2, N Skitareliã8, M Spajiã9 Depts. of pediatric nephrology, University Children,s hospitals Zagreb1, Rijeka2 and Split3, Dept. of Steroid-resistant nephrotic syndrome (SRNS) carries the worst prognosis with a high rate of pathology, Clinical Hospital Rebro, Zagreb4, Dialysis Dept., Clinical Hospital Rebro, progression to ESRD in children. Recent reports have identified the potential beneficial use Zagreb5, Clinical Hospital „Sestre Milosrdnice“ Zagreb6, Clinical Children,s Hospital of mycophenolate mofetil (MMF) as a new immunosuppressive agent for the treatment of a „Zagreb“7, Croatia, General Hospitals Zadar8 and Karlovac9 variety of glomerular diseases. University Children`s Hospital , Dept. of Nephrology, Salata 4 , 10000 Zagreb , Croatia The purpose of the study was to determine the efficacy of MMF in the treatment of SRNS in children. There is little data on the spectrum of renal diseases among children in Croatia. A renal Six children (4M/2F; mean age at the start of MMF 14.3±1.3 years (range 10.0-17.5); diseases registry has been set up recently in an attempt to address this issue nationwide. disease mean duration 4.3±1.8 years) were studied. Three of the six patients previously Here we report the results of a retrospective analysis of clinical and histopathological data received treatment with cyclophosphamide and 2 with cyclosporine A. Renal biopsy of 565 children presenting to 7 hospitals in Croatia from 1991 to 2004 in whom kidney showed FSGS (n=3) and mesangial proliferative glomerulonephritis (n=3). The mean initial biopsy was performed. The most common indications for biopsy were nephrotic syndrome dose of MMF was 16.8±1.6 mg/kg/day (range 0.75-1.0 g/day) with a following full dose (39.2%), asymptomatic proteinuria/hematuria (21.7%) and nephritic syndrome (16.9%). All 30.9±1.3 mg/kg/day (peak 2.0 g/day). The actual mean duration of the treatment with MMF biopsies were analysed by light, immunofluorescent and electronmicroscopy. Primary was 10.7±2.3 months (range 2.0-17.0 months). glomerular diseases accounted for 65.4% of all biopsies, followed by secondary (14.8%) All patients had a decrease of proteinuria from a mean level at entry of 8.7±3.6 to 2.2±0.6 and hereditary glomerular diseases (12.0%). Among primary glomerular diseases the most g/l (by -77% from baseline) during treatment with MMF. One child with FSGS achieved a frequent were focal segmental glomerulosclerosis (FSGS) (25.0%), mesangial proliferative partial remission of SRNS. Serum creatinine and albumin values, GFR and BP (according glomerulonephritis (MEPGN) (19.2%) and IgA nephropathy (18.2%). The most common to ABMP) remained stable during the MMF therapy. secondary glomerular diseases were Henoch-Schönlein purpura (HSP) ( 47.9%) and Our preliminary results demonstrate that the use of MMF in the treatment of SRNS in systemic lupus erythematosus (SLE) (35.4%). The most frequent hereditary glomerular children is effective in reducing proteinuria and well tolerated without any gastrointestinal disease was Alport syndrome (80.9%). In the group of children with primary glomerular or hematological side effects. Further controlled clinical trials are needed to define the role diseases who presented with nephrotic syndrome the most frequent were FSGS (38.5%) and of MMF in the management of SRNS in children. MEPGN (24.0%). Minimal changes glomerulopathy (MCG) accounted for only 10.9% cases. IgA nephropathy, primary or related to HSP, was the most common biopsy proven renal disease in Croatian children (20.0% of all cases). The analysis provided data on the frequency of histological renal lesions in children in Croatia. The higher frequency of FSGS among Croatian children in comparison with similar analyses in other countries deserves further evaluation.

COD. PP 347 COD. PP 348 The role of Osteopontin C-707T Gene Polymorphism in susceptibility Is urinary transforming growth factor beta-1 (TGF-1) a useful and outcome of Focal Segmental Glomerulosclerosis biomarker in idiopathic nephrotic syndrome (INS) of childhood? N Besbas*1, K Ozgul2, M Kalyoncu1, F Ozaltin1, A Duzova1, S Ozen1, R Topaloglu1, A I F Shatat, MD1, E O`Riordan, MD2, F J Kaskel, MD, PhD1 and R P Woroniecki, MD1. Bakkaloglu1 1Dept. of Pediatric Nephrology, 2Dept. of Medical Biology and Tübitak 1Pediatric Nephrology, Children`s Hospital at Montefiore of the Albert Einstein College of DNA/Cell Bank. Hacettepe University Faculty of Medicine, Ankara, Turkey Medicine, Bronx, NY, United States and 2Renal Institute, New York Medical College, Hacettepe University Faculty of Medicine , Dept.of Pediatric Nephrology Sihhiye , 06100 Valhalla, NY, United States. Presentin g auther: I F Shatat Ankara , Turkey , 3450 Wayne Ave. Apt#26 L , 10467 Bronx , NY USA

Osteopontin (SPP1), is upregulated in several human renal diseases showing interstitial Background: The response to steroid therapy is used to characterize the INS of childhood as fibrosis. either steroid sensitive (SSNS) or steroid resistant (SRNS). Factors that can contribute to the We investigated 59 Turkish patients (aged 74.347.9 months) diagnosed with FSGS based differences between the two groups remain unknown. on renal biopsy to clarify the association between polymorphism at position 707C>T in the Based on our prior data using protein microarray chips which showed greater urinary coding region of the osteopontin gene and susceptibility and outcome of FSGS. Gender and cytokine expression in SSNS as compared to SRNS and controls (Cs), we attempted to age-matched 96 healthy children and children with minimal change disease (MCD) served quantitate TGF-1 levels by analyzing urine samples from the same patient population. as controls. The osteopontin genotype was identified by PCR- RFLP analysis. The genotype Objective: To confirm and quantitatively measure the differences in urinary TGF-1 levels frequency of the patients was as follows: 19 (32.2%) patients had C/C genotype, 37 (62.7%) between SSNS, SRNS and Cs. patients had C/T, 3 (5.1%) patients had T/T genotype. The distribution of osteopontin Design/Methods: To determine differences in urinary TGF-1 between SSNS, SRNS and Cs, genotypes for these alleles were similar among patients with FSGS and MCD and healthy with a cross sectional study design and using ELISA we re-analyzed the urine samples of 30 controls. The clinical parameters at presentation including renal function and proteinuria did patients from our previous patient population; SRNS (n=9), SSNS (n=11), and C (n=10). not differ significantly between patients with different genotypes. Urinary TGF-1 levels (pg/ml) corrected for urine creatinine (mg/dl) did not follow a normal During the observation period, the incidence of chronic renal failure (CRF) was distribution and values are presented as medians±SEM. Non-parametric tests were used to significantly higher, despite a shorter mean follow-up period (44%). Progression of renal test for statistical significance. disease was observed in 8 (32%) patients with the C/C genotype, in 17 patients (68%) with Results: Mean age, gender, glomerular filtration rate (calculated using the Schwartz the C/T genotype. SPP1 C/T polymorphism did not reveal statistically significant difference formula), and body mass index were not statistically different between the groups. Urine in genotype frequency between patients with declining renal function (n=25) and in those protein to creatinine ratios were 0.19±0.12 in SSNS vs. 4.1±3.4 in SRNS, P=0.0013. with stable renal function (n=34). This distribution of genotype frequencies was not Using protein microarray chips, median urinary TGF-1 levels corrected to urinary creatinine statistically different from patient with normal renal function and the total collective of in SSNS and SRNS were higher by 4.7X, 1.3X above C respectively, P=0.003, however, patients with FSGS. Our study revealed no association between C/T polymorphism of the when measured by ELISA, SSNS and SRNS median urinary TGF-1 levels(pg/ml) corrected osteopontin gene and susceptibility and outcome of FSGS. to urinary creatinine were 5.8X, 1.9X greater than Cs respectively, but did not reach statistical significance, P=0.28. Conclusions: Protein microarray chips showed differences in urinary cytokine profiles and TGF-1 levels between SSNS and SRNS and Cs. Using ELISA, urinary TGF-b1 levels trended to correlate with the array results, but were not statistically significant. This discrepancy may be related to smaller sample size, test sensitivity. Pediatr Nephrol (2006) 21:1493–1635 1609

COD. PP 349 COD. PP 350 EXPRESSION OF P-GLYCOPROTEIN P IN LYMPHOCYTES OF The clinicopathologic findings in 231 cases with idiopathic nephrotic CHILDREN WITH NEPHROTIC SYNDROME TREATED WITH syndrome PREDNISONE Ahmadzadeh Ali*, Derakhshan Ali, Hakimzadeh Mehran1, Zolfigol Ali A Wasilewska, W Zoch-Zwierz, M Pietuczu k Ahwaz Jondishapour university of medical sciences , Pediatrics Nephrology Unit, Abouzar I Department of Pediatrics, Medical University in Biaùystok, Poland , Waszyngtona 17 , 15- Children`s Hospital , 61636 Ahwaz , Khoozestan Iran 274 Biaùystok , Poland Idiopathic nephrotic syndrome (INS) is a common renal disease, characterized by Glucocorticoids (GC) are still the mainstay of therapy for nephrotic syndrome in children. proteinuria, hypoalbuminemia, hyperlipidemia and edema. Light microscopy shows three Poor response to GC may relate in part to overexpression of P-glycoprotein P (P-gp). The morphology patterns: minimal change nephrotic syndrome (MCNS), mesangial proliferative aim of the present study was to determine the expression of P-gp in lymphocytes (CD3) in glomerulonephritis (MesPGN) and focal segmental glomerular sclerosis (FSGS).The the peripheral blood of children with steroid-sensitive nephrotic syndrome (SSNS), in the purpose of present study was to assess the type and outcome of disease in patients with NS. dynamics of the disease. Material and methods: The study group consisted of 18 children Through a retrospective study we reviewed the medical files of patients with NS. Over 8 with SSNS in whom the examinations were carried out three times: IA – before treatment, years, (1996 to 2004), among 285 edematous children, 231 had INS and followed up at least during relapse, IB – after 3-4 weeks of prednisone treatment, IC – 2 months after finishing for 2 years. prednisone treatment. The control group (II) consisted of 18 healthy children. P-gp The clinical characteristics, laboratory data and histological findings were analysed. There expression in lymphocytes of peripheral blood was measured using flow cytometry. were 161 males; the median age at presentation was 4.5 years, 72.6% between 2-6 years Results: During NS relapse (A) mean expression of CD3/P-gp (3.441.95%) was highe r old. Of 231 patients 87% were initial steroid responders and 33.7% nonrelapsers. Thirty when compared to healthy controls (II) (1.240.58%). It concerned mainly the children children were steroid resistants in whom 24 renal biopsies were done. The histopathologic with 1st –3rd relapse of NS, in whom the CD3/P-gp expression was 4.331.75%. Howeve r study showed FSGS in 9, MesPGN in 5, membranoproliferative glomerulonephritis and in children with first episode of NS the expression of P-gp was normal (1.66 0.68 %) MCNS each in 4, membranous glomerulonephropathy and rapidly progressive (p>0.05). After GC treatment (B) CD3/P-gp expression increased to 7.883.99%. In glomerulonephritis each in one. Of 201 steroid responders 123 were relapsers in whom 50% remission (C) over 70% of children still showed P-gp values above the cut-off level. We were frequent relapsers. Complete remissions were seen in 68.4% after stoppage of steroid. also found a positive correlation between the P-gp expression and total prednisone dose. Seventy patients had hematuria, 36 hypertension and 6 chronic renal failure. Five children Conclusions: The expression of P-gp increases in the course of GC treatment. died in who 4 had FSGS and one MesPGN. Overexpression of P-gp in remission, after finishing of GC treatment suggests that P-gp Conclusion: The majority of cases were steroid sensitive, but only 13% were steroid may be involved in worse response to corticosteroids in frequent relapse patients. resistants in who 50% had FSGS. We also found an association between hypertension, renal insufficiency and FSGS, whereas there was no correlation between (micro or macro) hematuria and this pathology.

COD. PP 351 COD. PP 352 Toxoplasmosis-associated congenital nephrotic syndrome: a causal or Remission of steroid and cyclosporine resistant nephrotic syndrome casual coincidence? using multiple drug immunosuppression P Toth-Heyn, I Mattyus, J Szolnoki, P Sallay, M Kardos, GS Reusz Ist Department of L Perrin, V Guigonis, A Bensman, G Deschênes, T Ulinski Pediatrics, Semmelweis University, Budapest Hôpital Trousseau , Department of Pediatric Nephrology , 75012 Paris , France Ist Department of Pediatrics , Bokay J. u. 53. , 1083 Budapest , Hungary Nephrotic proteinuria in minimal change disease (MCD) is due to a circulating factor of Infectious causes are among the etiologic factors of congenital nephrotic syndrome (CNS) immunologic origin. It is usually steroid sensitive. End stage renal failure occurs if besides of genetically determined structural defects of podocyte foot processes. The treatment with both steroids and immunosuppressive drugs such as cyclosporine A remains coincidence of CNS with toxoplasmosis has rarely been reported, toxoplasma infection is inefficient. still, however, considered as a pathogenic factor for CNS. Interestingly, only one new case Methods. Two girls (2 and 3 yrs) and one boy (6 yrs) with secondary steroid resistant of toxoplasma-related CNS has been described since the identification of podocin and nephrotic syndrome that remained resistant after 30 days of oral prednisone (60 mg/m2 per nephrin mutations. day) and 3 pulses of methylprednisolone (1g/1.73 m2) followed by 30 days of IV We report the case of a male infant presenting with generalized edema, hypoproteinemia cyclosporine (blood level 500 – 600 ng/ml) were treated with a multiple and proteinuria at the age of 5 weeks. In addition to his proteinuria a macroscopic hematuria immunosuppressive therapy including plasma exchanges (N=20), oral cyclophosphamide was observed and later he exhibited elevated blood pressure. Daily albumin infusions and (150 mg/kg over 90 days), oral cyclosporine A (blood levels 400-600 ng/ml) and high dose furosemid significantly increased his diuresis and resolved the edema. The methylprednisolone pulses followed by oral prednisone and pefloxacin. histological analysis of renal biopsy specimens revealed a non-specific mesangial Results. All three children went into remission within 2 to 5 weeks. After a follow up of 46, proliferation without significant sclerosis or immune-deposits. The serological tests 36 and 25 months respectively we noted late steroid sensitive relapses after 22 and 19 performed in order to exclude infectious origin of CNS found a rising titer of toxoplasma months respectively in the first two patients. The character of their NS changed into a IgM-IgA antibodies, differing from maternal antibodies, proving an active toxoplasma steroid sensitive one with a low to moderate degree of steroid dependence. Disease infection. Accordingly, long term spiramycin therapy was initiated. progression towards end stage renal failure could be avoided with low treatment toxicity on The proteinuria did not react on 6 weeks steroid treatment. Cyclosporine therapy was then the long term. All three children have normal renal function, normal blood pressure and introduced in view of steroid resistance and histological findings. There was a good negative proteinuria. response to cyclosporine or/and spiramycin therapy, leading to cessation of proteinuria. Conclusion. A cumulative immunomodulatory activity is believed to be responsible for the The genetic forms of CNS are implausible in our patient in view of good cyclosporine sustained remission after initial removal of a yet unknown circulating factor. sensitivity. The clinical improvement on spiramycin clearly suggests toxoplasmosis as the cause of CNS. Retrospective histological analysis seems to confirm the toxoplasmosis- related origin of renal pathology. 1610 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 353 COD. PP 354 Clinical and Histological Relapse of Membranous Nephropathy with ATYPICAL HEMOLYTIC UREMIC SYNDROME ASSOCIATED Anti Tubular Basement Membrane Antibodies in a Pediatric Renal WITH ANTI-FACTOR H ANTIBODIES IN A 11 YEAR OLD BOY Transplant Recipient E Balzamo, MA Dragon-Durey, V Frémeaux-Bacchi, R Salomon, MF Gagnadoux, P T Ulinski, V Baudet-Bonneville, H Debiec, B Mougenot, S Nathanson, G Deschênes, A Niaudet Bensman Service de Néphrologie Pédiatrique, Hôpital Necker-Enfants Malades , 149, rue de Sèvres , Hôpital Trousseau , Department of Pediatric Nephrology , 75012 Paris , France 75015 Paris , France

Membranous nephropathy with antitubular basement membrane antibodies is a rare A 11 year old boy was admitted because of vomiting and asthenia. He presented with condition. Relapse of tubular dysfunction in renal transplant recipients has been published jaundice, edema, high blood pressure and macroscopic haematuria. Biological evaluation in one case, but a relapse of membranous nephropathy in the renal graft has not yet been showed haemolytic anemia (haemoglobin, 5.2g/dL), thrombocytopenia (platelets, 43 X reported. 109/L), proteinuria, 12 g/L and renal failure (serum creatinine, 239 µmol/L). He first A 3-year old boy presented first with steroid resistant nephrotic syndrome associated to received fresh frozen plasma (FFP) daily for 7 days. Serum reatinine remained stable tubular dysfunction. Renal biopsy revealed membranous nephropathy with interstitial (190µmol/L) and platelet count increased to 109 X 109/L. When FFP infusions were given fibrosis and granular deposits of IgA, IgG, and C3 along the tubular basement membrane. every other days, he developed a relapse with thrombocytopenia (25 X 109/L) and an Indirect immunofluorescence revealed circulating anti-tubular basement membrane increase of serum creatinine (308µmol/l). Three weeks after admission, he was treated with antibodies. Was transplanted at the age of 6 years. plasma exchanges (PE) (11 sessions) with FFP replacement, followed by an improvement An acute rejection episode on day 21 required three steroid pulses and OKT-3. Renal biopsy of renal function, an increase in platelet count and reversal of hemolysis. revealed the presence of interstitial and vascular rejection (BANFF III) and relapse of Plasma concentrations of C3, C4, factor B, factor H (FH), factor I and ADAMTS 13 activity tubular basement membrane deposits. Renal function normalized within 10 days and were normal. PCR for Shiga-toxin in the stools and detection of serum antibodies against remained stable (GFR estimated by Schwarz formula = 103 ml/min per 1.73). Proteinuria LPS were negative. High titers of anti-FH antibodies (isotype IgG3) were detected by remained negative and urinalysis normal over 5 years under the immunosuppressive ELISA on a serum at admission. A decrease of the antibodies titer was observed following regimen including FK, AZT, and prednisone. At the age of 11 years proteinuria increase d PE. progressively over 6 weeks reaching 2.8 g/day, whereas serum creatinine was stable. Renal In a recent report, anti-FH antibodies were detected in 3 out of 48 children with atypical biopsy revealed granular deposits along the glomerular basement membrane suggesting a HUS (J Am Soc Nephrol 2005; 16: 555). Together with this observation, it shows that late relapse of membranous nephropathy in the transplant. Rituximab therapy (day 0, 15, 30, atypical HUS may occur in the context of an autoimmune disease. PE are effective in and 60) followed by switch from AZT to MMF resulted in a complete biological remission removing anti-FH antibodies and the indication of additional immunosuppressive treatment with negative proteinuria. This is the first report of glomerular relapse of membranous should be discussed. nephropathy with anti tubular basement membrane antibodies in a renal transplant recipient.

COD. PP 355 COD. PP 356 Post-transplant Glomerulonephritis with Isolated C3 Deposits in Two Outcome of Henoch-Schönlein purpura nephritis after Children with Factor H Deficiency and Atypical Hemolytic and Uremic cyclophosphamide therapy Syndrome on Native Kidneys M Bald, M Holder, HE Leichter Pediatric Nephrology, Olgahospital Stuttgart, Germany O Boyer, V Frémeaux-Bacchi, E Balzamo, N Biebuyck, MF Gagnadoux, LH Noël, R Olgahospital , Bismarckstr. 8 , D-70176 Stuttgart , Germany Salomon, P Niaudet Service de Néphrologie Pédiatrique, Hôpital Necker-Enfants Malades , 149 rue de Sèvres , The outcome of Henoch-Schönlein purpura (HSP) nephritis is in general good. However if 75015 Paris , France patients develop nephrotic syndrome and/or decreased renal function during initial presentation, approximately 20 % of them develop long term renal sequelae. We report the first cases of atypical hemolytic uremic syndrome (HUS) associated with Between 1998 and 2005 thirty patients with HSP nephritis were seen in our Pediatric factor H (FH) deficiency on native kidneys and glomerulonephritis (GN) with C3 deposits Nephrology Department. Seven out of these patients including four boys and three girls after renal transplantation. with a mean age of 6 years (range 3 – 10 years) presented with severe HSP including skin, A 16 month old boy developed atypical HUS with low C3, low FH activity (40%), and joint and intestinal involvement as well as HSP nephritis. Five of them were nephrotic, one glomerular thrombotic microangiopathy (TM). Genetic studies revealed a heterozygous FH patient had decreased renal function and one patient was nephrotic with decreased renal mutation, a heterozygous FI mutation, and a rare CD46 polymorphism. Despite fresh frozen function. Renal biopsy showed crescents (mean 50 %) and subepithelial deposits in all plasma (FFP), he rapidly reached end-stage renal failure (ESRF), and was transplanted. Five patients. All were treated with prednisone 2 mg/kg/d which was slowly tapered as well as years later, GFR declined from 120 to 67ml/min/1.73m2. Blood cell count and urinary cyclophosphamide (1.6-2.2 mg/kg/d) for 8 weeks. After 8 weeks of therapy renal function sediment were normal. Renal histology revealed numerous mesangial and extramembranous was within normal limits (mean GFR 125 ml/min/1.73m², range 112-172), but microscopic C3 deposits, and grade 1 chronic allograft nephropathy (CAN1), with no sign of TM. Seven haematuria was present in all 7 patients and 4 of them had still nephrotic range proteinuria. years post-transplantation, he was asymptomatic, with stable GFR. After 2 years of follow-up no patient had major renal sequelae (proteinuria, hypertension or A 11 month old boy developed atypical HUS with low C3 level, low FH activity (3%) an d decreased renal function) with the exception of microscopic haematuria in 3 out of 5 TM on renal biopsy. He had a FH homozygous mutation. Recurrence of hemolytic anemia 7 patients. days following renal transplantation was treated with FFP. Five months later, transplant Our results indicate a favourite outcome in children with severe HSP nephritis treated with biopsy showed CAN1 and isolated mesangial and extra-membranous C3 deposits, with no prednisone and cyclophosphamide for 8 weeks. More studies (multicenter) to validate the sign of TM. Four years later, a second biopsy performed for a decreased GFR concomitant potential benefit of immunosuppressive therapy are needed. to a pulmonary infection showed TM associated with diffuse mesangial C3 deposits and CAN1. A transient increase of FFP infusions permitted a raise of GFR, and 5 years post- transplantation, GFR was stable. These observations suggest that GN with isolated C3 deposits and TM may be different expressions of the same disease. Pediatr Nephrol (2006) 21:1493–1635 1611

COD. PP 357 COD. PP 358 Association of thin basement membrane nephropathy (TBMN) with A Case Of ANCA-associated Pauci-immune Crescentic glomerulonephritis in children. Glomerulonephritis In Juvenile Rheumatoid Arthritis M Ignatova1, L Prikhodina1, E Golitsina2, V Varshavsky2, D Fedorov1, V Dlin1 Y S Hwang1(presenting author), J S Lee1, H J Jeong2 Department of Pediatrics1, The Moscow Institute of Pediatrics & Children Surgery , Taldomskay ST, 2 , 125412 Moscow , Institute of Kidney Disease1, Department of Pathology2, Yonsei University, College of Russia Medicine, Seoul, Korea Yonsei University College of Medicine , Department of Pediatrics, Yonsei University In spite of TBMN is the most common cause of persistent hematuria in children data on its College of Medicine, 134 Shinchon-Dong, Seodaemun-Ku , 120-752 Seoul , South Korea association with other GN and prognosis are limited. The aim of this study was to investigate of prevalence, clinical features and prognosis of [Background] TBMN in children. Juvenile rheumatoid arthritis(JRA) is the most common major connective tissue disease in From January 2004 to December 2005, findings from 52 native kidney biopsies done for children. Renal involvement in JRA is rare. Among the renal lesions, amyloidosis and drug- evaluation of renal disease were retrospectively studied. The overall prevalence of TBMN induced nephropathy are the most common and crescentic glomerulonephritis has rarely (the mean diffuse GBM thickness was <200 nm) was 19.2% (10 of 52). been reported. We followed ten children (5M/5F), mean age 8.9±1.8 years (range 5 – 17) with TBMN [Case presentation] associated with persistent microscopic hematuria in all of them; 3 of 10 patients presented A 15-year old boy presented with fever and gross hematuria for 2days, and vomiting and with nephrotic syndrome and normal renal function (2 patients has steroid-resistant NS). headache for 2weeks. He was diagnosed with systemic JRA 3years ago and treated with Renal biopsy showed mesangial proliferative glomerulonephritis in all cases including 4 several drugs. He had renal impairment and aseptic meningitis. Laboratory investigations patients with IgA nephropathy. Under immunofluorescence microscopy 4 cases were showed BUN/Cr 43/5.4mg/dL, ASO 120IU/mL, C3 54.9mg/dL, C4 19.1mg/dL, p-ANCA; positive for IgA, 2 for IgM and 2 for complement. No apparent evidence of familial positive, c-ANCA; negative, anti-MPO;271U, anti-proteinase3; negative, anti-GBM; hematuria in any patients was noted. negative, 24hr protein 46mg/m2/h, CCr 13.7mL/min/1.73m2. We started to treat aseptic After a mean follow up period of 24.0±6.5 months all children has microscopic hematuria meningitis and performed a kidney biopsy on the 4th day. Because the pathologic finding and mild proteinuria (0.38±0.099g/l), 20% (2 of 10) patients has hypertension and no renal showed Pauci-immune Crescentic progression (mean GFR 97.2±8.2 ml/min). Glomerulonephritis, we performed 3day course of methylprenisolone, followed by daily The present data indicate that patients with TBMN often have concomitant mesangial oral prednisolone. proliferative glomerulonephritis, particularly IgA nephropathy. The TBMN is considered to His renal function recovered gradually and became normal after 2 months. p-ANCA and be the pathological basis and predisposing alteration to GN, leading in time to increased anti-MPO became negative and C3 level was in the normal range. But he continued to proteinuria and incidences of hypertension. present with heavy proteinuria, so he was treated with cyclophosphamide for 12weeks. Even after cyclophosphamide treatment, urinalysis showed microscopic hematuria and proteinuria. We performed second renal biopsy. Now he is taking azathioprine, prednisolone and enalapril.

[conclusion] We experienced p-ANCA associated Pauci-immune crescentic glomerulonephritis in JRA and further studies are needed to define the role of JRA in these renal disease.

COD. PP 359 COD. PP 360 GROWTH AND FUNCTION OF THE RADIOLOGICALLY ACE Gene Polymorphism in Children with Henoch-Schonlein Purpura NORMAL SOLITARY KIDNEY DURING CHILDHOOD AND 1H Dursun, 1A Noyan, 1A K Bayazit, 1U S Celik, 2S Matyar, 1M Soran, 1M Buyukcelik, ADOLESCENCE 2G Attila,3N Cengiz, 1A Anarat Çukurova University School of Medicine, Departments of E Siomou1, F Papadopoulou2, A Fotopoulos3, A Katsaraki4, A K Mavridis5, A 1Pediatric Nephrology and 2 Biochemistry, Baskent University School of Medicine, Adana Siamopoulou1 Departments of Pediatrics1, Radiology2, Nuclear Medicine3, Statistics4, Research Hospital, Department of 3Pediatric Nephrology, Adana, TURKEY University Hospital of Ioannina and Laboratory of Microbiology, General Hospital Cukurova University School of Medicine , Department of Pediatric Nephrology , 01330 Chatzikosta5, Ioannina, Greece Adana , Turkey , EMMANOUIL XANTHOU 58 , 45445 IOANNINA , Greece The aim of this study is to investigate the effect of the angiotensin converting enzyme Compensatory hypertrophy and hyperfiltration of the solitary kidney (SK) has been found, (ACE) gene polymorphism on presentation and progression of children with Henoch- by experimental studies, to lead to focal glomerulosclerosis and loss of renal function. Schönlein purpura (HSP). We examined the insertion (I) and deletion (D) polymorphism in In order to estimate the growth and functional parameters of the radiologically normal SK, intron 16 of ACE gene by PCR amplification of genomic DNA of 54 children (1.5-17 years 25 children, aged 8-16 years, were studied (13 with congenital SK and 12 with acquired old at onset) with Henoch-Schönlein purpura. ACE genotypes, urine protein, haematuria from infancy). Twenty five healthy children, age and sex matched, were used as controls. and creatinine clearance were analyzed, and blood pressure was measured. Patients were Urinary tract ultrasound, Doppler sonography, 24-h creatinine clearance (CrCl), total divided into 3 groups as HSP nephritis group (14 patients), HSP with minor urinary protein excretion and screening for microalbuminuria were performed in patients and anomaly group (18 patients) and HSP without renal involvement group (22 patients). The controls. DTPA-GFR was performed only in patients. distribution of ACE genotypes in HSP nephritis was II (7%), ID (57%), DD (36%); in HSP The values of SK volume were higher, compared to controls (right kidney: 234.1±89.3 and with minor urinary anomaly was II (0%), ID (89%) DD (11%); and in HSP without renal 133.9±40.2 cm3 respectively, p=0.002 and left kidney: 209.8±83.4 and 130.5±37.2 cm3 involvement was II (5%), ID (72%), DD (23%). No association was found between the respectively, p=0.02). The resistance index of interlobar and arcuate arteries did not diffe r ACE genotype and the presence of renal involvement (÷2=4.39, p=0.356). DD genotype between patients (0.56±0.05 and 0.54±0.06) and controls (0.55±0.03 and 0.53±0.03). The was seen in 5 (42%), 2 (16%) and 5 (42%) of the patients with HSP nephritis, HSP with values of ClCr in patients (103.8±23.8 ml/min/1.73 m2) did not differ, compared to controls minor urinary anomaly and HSP without renal involvement patients respectively. In HSP (101.1±23.9 ml/min/1.73 m2) and did not correlate significantly with those of DTPA-GFR patients blood pressure and creatinine clearance were not significantly different among the (93.7±25.9 ml/min/1.73 m2). The 24-h protein excretion did not differ significantly between three genotypes. These results do not support an association between disease severity and patients and controls (93.2±66.7 and 65.4±23.3 mg/24h respectively), whereas the DD genotype in children with HSP; however larger studies are required to confirm this. microalbuminuria was slightly higher in patients, compared to controls (7.8±7.2 and 4.5±2.5 mg/24h respectively, p=0,06). In conclusion, the hyperfiltration of SK did not associate with findings of glomerulosclerosis, at least during the first 8-16 years of life. The follow-up is necessary to evaluate if the relatively higher microalbunuria in patients represents an early finding of future glomerulosclerosis. 1612 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 361 COD. PP 362 The morphological structure of nephropathies with the syndrome of Differential diagnostics of syndrome of isolated microscopic hematuria isolated microscopic hematuria in children in children Igor Zorin, Alexey Tsygin, Albina Vyalkova Albina Vyalkova, Igor Zorin, Alexande r Karpov, Boris Frolov, Yuriy Kopylov Scientific Center of children’s health of the Russian Academy of Medical Sciences, , Matrosskij pereulok, 22, kv.4 , 460000 Orenburg , Russia Moscow, Orenburg medical academy, Russia , Matrosskij pereulok, 22, kv.4 , 460000 Orenburg , Russia Isolated microscopic hematuria is one of the most difficult symptoms for differential diagnostics of renal and urological diseases. That’s why the aim of the study was to The aim of the study was to create morphological structure of nephropathies with the investigate the significance of osmotic resistance of urine erythrocytes in children with syndrome of isolated microscopic hematuria in children.We evaluated clinical features, isolated microscopic hematuria. We examined 60 patients with isolated microscopic laboratory data and histopathology of 121 children with the syndrome of isolated hematuria. hematuria persisting for more than 1 year. They were divided into two groups: Nephrobiopsy was performed, when non-glomerular causes were excluded. Indication for 1) with postrenal hematuria due urolithiasis (n=30), biopsy was microscopic isolated hematuria for more than 1 year. Renal tissue was studied 2) with glomerular hematuria due acute glomerulonephritis (n=30). with light, immunofluorescence and electron microscopy. The commonest cause of Definition of osmotic resistance of urine erythrocytes was carried out by our original nephropathies with the syndrome of isolated microscopic hematuria in children was method. The essence of the method consisted in quantitative calculation of urine mesangial proliferative glomerulonephritis in 29 patients (24,2%) followed by focal erythrocytes after 30 minutes of endurance in 0,45 % solution of NaCl. We established that segmental glomerulosclerosis and membranoproliferative glomerulonephritis in 17 (14 %) osmotic resistance of urine erythrocytes 49,83 + 3,53 % is characteristic for glomerular patients each, hereditary nephritis in 12 (10 %), chronic tubulointersticial nephritis in 10 hematuria, 65,09 % + 4,96 % is characteristic for postrenal hematuria (urological diseases). (8,2 %) cases, IgA nephropathy in 9 (7,4 %), endocapillary proliferative glomerulonephritis The ranges of the osmotic resistance of urine erythrocytes were significant different and membranous glomerulonephritis in 8 (6,6 %) patients each, minimal change disease in between children from comparing groups (p<0,0001). That’s why determination of osmotic 4 (3,3 %), exstracapillary glomerulonephritis in 3 (2,5 %) cases, thin glomerular basement resistance of urine erythrocytes can be used to differentiate glomerular and postrenal membrane disease, renal dysplasy, endocapillary exudative glomerulonephritis, IgÌ diseases in children with isolated microscopic hematuria. nephropathy in 1 (0,8 %) patients each.

COD. PP 363 COD. PP 364 Nephrotic state and high dose glucocorticoids do not inhibit serological CHILDREN IN CZECH REGISTRY OF RENAL BIOPSIES - 10 response to pneumococcal vaccine in children with the nephrotic YERS OF EXPERIENCE syndrome A Kolsky, E Jancova, I Rychlik, J Dusek, M Hladik, S Skalova, Z Pellantova, P Geier, V T Ulinski, M Dubrel, G Deschenes, A Bensman Rambousek, V Smrcka, J Starha, J Skibova, M Kolska, J Stejskal, J Janda, V Tesar et al., on Hôpital Trousseau , Department of Pediatric Nephrology , 75012 Paris , France behalf of the Czech Registry of Renal Biopsies , Dept. of Paediatrics, Thomayer Teaching Hospital, Videnska 800 , 140 59 Prague 4 , Nephrotic children are at risk for severe pneumococcal infections. Anti-pneumococcal Czech Republic vaccination is performed in many centers, but the best moment for the vaccination is controversially discussed. We investigated the serologic response after Pneumo23 Aim of Study: This report describes data collected by the National registry of renal biopsie vaccination in 19 children (5 girls, aged 3-18.3 years) with the nephrotic syndrome, (CRB) which includes 1434 renal biopsies (RB) in children and adolescents 18 years in immediately after the beginning of daily prednisone therapy at 60 mg/m2. All children had the years 1994-2003. CRB has been run since 1994 and includes currently 10 paediatric nephrotic range proteinuria and hypoalbuminemia at the time of vaccination. centres performing practically all RB of native kidney in children. Results: Mean age 12.6 Pneumo23 antibody level at presentation (M0) was 1.34±0.30 g/ml (mean±SE). Thirty 4.5 yrs (2.5 months - 18 yrs), boys 55.9%., girls 44.1%. 9.5% of children were 5 yrs, days after vaccination (M1) antibody levels increased 8-fold to 10.84±1.61 g/ml 21.3% were 5-10 yrs, 35.8% were 10-15 yrs and 33.6% were 18yrs. Concerning the (p<0.0001). Serum levels at M3 were 7.58±1.67. One year (M12) after vaccination antibody occurrence of renal diseases, primary glomerulonephritis (GN) (65.3%) and secondary GN levels remained increased (4.4±1.78) compared to M0 (p<0.01). However, there was a (25.7%) were the most frequent. The ratio of primary to secondary GN is decreasing in significant decrease compared to M1 (p<0.01). There was no increased delay until linear trend for time in this decade (from 7.7:1 to 4.8:1). The most common primary GN remission compared to a retrospective control group. Severe hypoalbuminemia (<7g/L) at were IgA GN (24.1%) and minimal change disease (10.1%). Secondary GN included thin- the time of vaccination was related to a lower baseline antibody level and a lower membrane glomerulopathy (12.3%), Alport syndrome (4.6%), Lupus nephritis (4%) and serological response on M1. However, antibody levels increased at least 2-fold in all Henoch-Schönlein purpura (2.8%). Out of all RB microscopic haematuria (HU) was present patients. in 60%, gross HU in 14.7%, proteinuria (PU) in 64% (22.6% 3,5g/24h). 12% of patients Conclusion. We demonstrated that nephrotic children on high dose glucocorticoid therapy were hypertonic and had significantly higher PU and level of plasma creatinine. 79.3% of respond well to anti-pneumococcal vaccination. Vaccination immediately after diagnosis o f RB were performed using ultrasound needle guidance, in 28.4% biopsy gun was used. nephrotic syndrome (NS) allows synthesis of protective antibodies even for children with Clinically serious complications were in 3.4% of patients (gross HU, hematoma). steroid dependent or steroid resistant forms of the NS, whereas a vaccination after tapering Conclusion: RB provides us important information about the epidemiology of GN in Czech of steroid doses would delay the development of a protective antibody level. Those patients Republic, about indications for performing RB and represents a base for co-operation in this who relapse during or after tapering off steroids have an increased Pneumo23 antibody level field. at the time of relapse. Pediatr Nephrol (2006) 21:1493–1635 1613

COD. PP 365 COD. PP 366 Fibrillary glomerulonephritis (FGN)-do we know enough to make firm MYCOPHENOLATE MOFETIL TREATMENT IN CHILDREN conclusions? WITH PRIMARY MEMBRANOPROLIFERATIVE M Bazina, M Saraga, M Glavina-Durdov, M Scukanec-Spoljar, D Vukic-Kosuljandic, M GLOMERULONEPHRITIS. Saraga-Babic Presentig author: M Saraga T Voznesenskaya, T Sergeeva, A Tsygin. Research Center for Child Health, Moscow, Clinical Hospital Split , Department of Pediatrics, Spinciceva 1 , 21000 Split , Croatia Russia. Croatia Research Centre for Child Health , Pediatric Nephrology, Lomonosovsky pr. 2/62 , 119991 Moscow , Russia Among the 65 children, that underwent kidney biopsy at Clinical Hospital Split in the 10- years long period, 27 (42%) had nephrotic syndrome. Out of 27 patients with nephrotic The aim of this study was to evaluate the efficacy of MMF treatment fot children with syndrome, in 18 patients (66%) biopsy was indicated because of inappropriate response to membranoproliferative glomerulonephritis. steroid therapy (dependence or resistance). In that group three patients (16,6 %) showed MMF was administered to 5 children with steroid-resistant nephrotic syndrome in whom pathohistological picture of FGN. Commonly, FGN was reported in literature as sporadic, the results of histopathological evaluation revealed type I membranoproliferative extremely rare condition, usually presented with steroid dependant nephrotic syndrome with glomerulonephritis. All patients had hematuria and hypertension, and 2 of them elevated progression in the end stage of renal disease (ESRD) in approximately 50% of patients, serum creatinine. during the period of 4 years after diagnosis. Histologically, it was characterised by presence The mean age at the presentation of the disease was 12,2 years. Before the MMF treatment of randomly oriented, unbranched fibrils of 10-12 nm in diameter, found in mesangial all patients were treated with intravenous pulse methylprednisolone. matrix, glomerular basement membrane, even extraglomerulary in other organs. Our study The mean age at treatment with MMF was 13 years. The mean dose of MMF was 1000 showed that FGN was really steroid dependant or resistant, but also showed higher mg/m² per day. The course duration was 12-14 month. All children received oral incidence of appearance, milder clinical course and better response to combined therapy prednisolon (1-2 mg/kg/day) and inhibitors of angiotensin converting enzyme (5-10 mg/day (cyclosporine and prednisone) than claimed in the literature. All of our three patients enalapril). In all the patients the dose of prednisolone was gradually decreased after 6-8 achieved remission with combined therapy, and all of them have still normal glomerular months of treatment. filtration rates. The mean period passed from the kidney biopsy in all three patients is All the patients responded to the treatment within 1-6 month after MMF was started: presently 3 years and 6 months. In conclusion, we would like to stress that incidence of 3 of them had achieved complete remission, 1 - partial remission, urinary protein level was FGN is probably underestimated, and we are convinced that incidence of FGN would rise decreased in 1 patient. There were no any side effects of MMF. At the end of the follow-up with routine use of electron microscopy for ultrastructural analyses of biopted kidneys, MMF was discontinued in 3 patients and all of them were in stable remission, in all patients especially in the group of children with steroid resistant or dependant nephrotic syndrome. serum albumin and serum creatinine were in normal limits. Conclusion: MMF with oral prednisolone may be an efficient treatment for children with type I membranoproliferative glomerulonephritis.

COD. PP 367 COD. PP 368 All antenatal membranous nephropathies are not secondary to Genetic Influence on Recurrence of Focal Segmental Glomerulosclerosis alloimmunisation against neutral endopeptidase (FSGS) in Paediatric Renal Transplantation: Results from the ECoFTS 1 V Guigonis 2 H Debiec 3 M Fiorenza 4 G Darreye 5 S Collardeau 6 MC Gubler 2 P T Jungraithmayr1, P Cochat2, S Fargue2, A Clara1, K Hofer1, S Weber3, G Cortina1, LB Ronco 5 R Bouvier 1 Department of Pediatrics, Hopital Dupuytren, Limoges, France 2 Zimmerhackl1 for the European Collaborative FSGS Transplantation Study (ECoFTS) INSERM U702/UPMC, Hopital Tenon, Paris, France 3 Department of Obstetrics, Hopital (http://ecofts.uklibk.ac.at) Departments of Paediatrics, Universities Innsbruck1, Austria, Dupuytren, Limoges, France 4 Department of Pathology, Limoges, France 5 Department of Lyon2, France and Heidelberg3, Germany Pathology, Hopital Edouard Heriot, Lyon, France 6 INSERM U574, Hopital Necker,Paris, , Universitätsklinik für Kinder- und Jugendheilkunde , 6020 Innsbruck , Austria France CHU Dupuytren , Department of pediatrics 8 Ave Martin Luther King , 87000 Limoges , Renal transplantation (RTx) in steroid resistant FSGS is complicated by high risk of disease France recurrence (DR). DR seems to be influenced by genetic background. 69 patients (p) with childhood onset of biopsy proven FSGS who had been transplanted at Introduction. We recently described 3 families with antenatal membranous nephropathies - least once were evaluated using a standardized questionnaire. Podocin mutations were occurring in fetuses - due to alloimmunisation against neutral endopeptidase (NEP) in their evaluated by genetic screening in 28 patients. mothers. Here we report a case of membranous nephropathy in a fetus with no NEP Of 69 patients 57 were Caucasians, 6 Arabs, 1 Asian and 5 others. Mean age at diagnosis alloimmunisation in the mother. Case presentation. A healthy 31-years-old woman was was 5.3+0.6 years (mean+SEM). The first RTx was done at age 11.4+0.8 years. 17 received referred to our prenatal diagnosis centre in her second pregnancy (after a miscarriage) at 17 a living related (LRD), 44 a deceased donor graft (DD), 8 data missing. 30 patients recurred weeks of gestation with sonographic abnormalities in her fetus. Sonographic findings (44%) after a mean time of 4.4+0.7 years (median 2.0 years), 22 with a DD (50%), 4 with included: intrauterine growth retardation, bilateral ventriculomegaly, oligohydramnios and LRD (24%), n.s.. 19 patients lost their graft (28%) after 8.0+5.2 years (mean+SEM, median hyperechogenic kidneys. At 19 weeks of gestation, a medical abortion was performed 3.8 years), 11 of those (58%) due to recurrence. A second transplantation was performed in considering the abnormalities’ severity. Fetal autopsy confirmed the sonographic findings 11 patients, all with a DD graft. DR occurred in 5 out of 7 patients (71%), data of 4 p were and additionally revealed that hydrocephalus was secondary to a sacral neural tube defect missing. Screening for podocin mutation revealed 5 patients with mutation. None of those and showed an enlargement of the spleen and the liver. Abundant extramedullary recurred compared to 13 recurring patients out of 20 p without NPHS2 mutation (p<0.05). haematopoiesis and siderosis present in different tissues associated with fibrosis of the liver Treatment of DR with plasmapheresis, cyclophosphamide and/or cyclosporine A had no was consistent with neonatal haemochromatosis. Careful microscopic examination of the significant positive effect on graft survival. kidneys allowed to reveal a membranous nephropathy. Similar deposits as those seen in the Prevention of recurrence remains a major challenge. Transplantation in patients with glomerular basement membrane were found in the adrenal glands. No anti-NEP reactivity podocin has lower DR.LRD kept their advantage regarding graft survival. A prospective was detected in the mother’s serum by indirect immunofluorescence or Western Blot transplant study in FSGS patients is urgently needed. analysis.Conclusion. Membranous nephropathy (or other antenatal nephropathies) should be looked for in cases of unexplained oligohydramnios. Other causes than alloimmunisation against NEP may lead to an antenatal-onset of membranous nephropathy. 1614 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 369 COD. PP 370 PODOCYTOPATHY OR FUNCTIONAL IMMATURITY OF Clinical Value of Autoantibodies against C1q in Children with GLOMERULAR FILTRATION BARRIER MIMICS Glomerulonephritis. GLOMERULOSCLEROSIS IN CHILDREN WITH NEPHROTIC I Kozyro, I Perahud, S Sadallah, A Sukalo, N Tur, L Titov, J Schifferli, M Trendelenburg SYNDROME: AN IMMUNOHISTOCHEMICAL APPROACH Belarus State Medical University , 2nd Childrens Hospital, Narochanskaja street 17 , D Ostalska-Nowicka, J Zachwieja, M Zaniew, M Nowicki1, A Siwi ñska, M Witt 2 220104 Minsk , Belarus Belarus Departments of Pediatric Cardiology and Nephrology, 1Histology and Embryology University of Medical Sciences in Poznan, 2Anatomy, University of Technology Dresden, Autoantibodies against the first component of the classical pathway of complement (anti- Germany C1q) can be found in a number of autoimmune, renal and infectious diseases. They are best University of Medical Sciences , Department of Pediatric Cardiology and Nephrology , described in adult patients with systemic lupus erythematosus (SLE) where a strong Szpitalna St. 27/33 , 60-572 Poznan , Poland Poland correlation between the occurrence of anti-C1q and severe lupus nephritis has been observed. However, the role of anti-C1q in children with SLE has not yet been determined. Idiopathic nephrotic syndrome in children may be complicated by the resistance to steroids Furthermore, the clinical importance of anti-C1q in other forms of glomerulonephritis (GN) which occurs mainly in diffuse mesangial proliferation (DMP) and focal segmental remains to be elucidated. The aim of this study was to investigate anti-C1q in children with glomerulosclerosis (FSGS).In our observation, in steroid-resistant nephrotic syndrome, the different forms of GN including lupus nephritis (LN). immature renal glomeruli can be detected (hypercellularity and a constant layer of cubical 112 children with different forms of GN were prospectively investigated for the presence of epithelial cells on the surface of glomerular tufts, without sclerosis, resembling M-stage of anti-C1q by an enzyme-linked immunosorbent assay and compared to 40 healthy controls. glomerulogenesis). At the electron microscopical level they possess podocytes not only on Associations between anti-C1q and disease manifestations at the time of the measurements the surface of glomerular tufts but also in the central part of the renal corpuscle. The and during follow-up were investigated. concept, that podocytes are the major culprit in the progression of glomerular diseases, is 21/112 patients were positive for anti-C1q compared to 0/40 healthy controls (p<0.001). gaining substantial ground due to their complex cytoskeletal machinery.The aim of this Anti-C1q were associated with activity in LN, and with disease severity in patients with study was the immunohistochemical analysis of the podocyte-associated proteins (ezrin, acute post-streptococcal GN (APSGN). In LN, 7/12 patients were found to be anti-C1q podocalyxin,synaptopodin and nephrin) in the renal glomeruli with, and without, signs of positive. 6 of these 7 had active disease at the time of the serum sampling compared to 1/5 immaturity in children with DMP and FSGS. In DMP with signs of immaturity podocytes in of the anti-C1q negative children (p<0.05). In children with APSGN, 8/24 were positive for the central region of the glomerulus were immunohistochemically negative.A positive anti-C1q. Anti-C1q positive APSGN patients had significantly higher proteinuria reaction was observed in the most superficial, continuous ‘layer’ of podocytes. This (p<0.0001) and more often hypertension (p<0.05) than those without anti-C1q. All 4 distribution mimicked the immunohistochemical pattern observed in FSGS, in which the patients in which APSGN did not resolve spontaneously were anti-C1q positive (p<0.01). central part of the glomerulus was occupied by foci of sclerosis.The initial steroid resistant Conclusions. Anti-C1q are associated with active lupus nephritis in children. In addition, course of nephrotic syndrome in children with signs of glomerular immaturity may be a children with anti-C1q positive APSGN have more severe disease than those who are anti- consequence of decreased glomerular filtration area defined by the absence or dysfunction C1q negative. These data suggest APSGN is another disease in which anti-C1q have a of cytoskeleton-associated proteins, namely ezrin, synaptopodin and nephrin, in podocytes pathogenic role. located in the central region of renal corpuscles

COD. PP 371 COD. PP 372 Successful medical treatment of extensive cerebral thrombosis in a child Mesangiocapillary glomerulonephritis with isolated anti-C1q with steroid-resistant nephrotic syndrome autoantibody. MK Lee (presenting author), JH Lee, YS Park Department of Pediatrics, Asan Medical Johnson SA, De S, Lane PJL, Milford DV, Ta ylor CM. Center, University of Ulsan, College of Medicine, Seoul, Korea Birmingham Childrens Hospital and University of Birmingham , Dept Nephrology, Dept Asan Medical Center , Department of Pediatrics, Asan Medical Center Pungnap 2(i)-dong Renal Immunobiology , B4 6NH Burmingham , UK UK Songpa-gu , 138-736 Seoul , South Korea Two boys aged 7 and 13 years presented with hypo-complementaemic, steroid resistant Introduction: Thrombosis is a complication of nephrotic syndrome which frequently occurs nephrotic syndrome with no preceding illness apart from mild urticaria in one. There were in femoral, mesenteric, or pulmonary veins but thrombosis in cerebral vessel is rare. We no features of systemic lupus erythematosus (SLE). Both children were normotensive and report a case of extensive cerebral thrombosis in a child with steroid-resistant nephrotic had normal renal function initially and have been followed for 3 and 1 years respectively. syndrome who were successfully recovered after warfarin and aspirin administration and Investigations were as follows:(table) remission of nephrotic syndrome by cyclosporine. Case: A nine-year-old boy was admitted to our hospital for kidney biopsy due to steroi d resistant nephrotic syndrome. He complained of abdominal pain and severe pulsatile frontal *normal range 0-15 units/ml headache. Generalized edema was noticed. Blood pressure was 110/67 mmHg and heart rate 101/min. Hemoglobin was 17 g/dL, hematocrit 51.2%, platelet 266,000/mm3, protein Histology showed mesangiocapillary glomerulonephritis (MCGN) with extensive deposits 5.3 g/dL, albumin 1.8 g/dL, cholesterol 380 mg/dL, PT 0.86 INR, aPTT 43.3 sec (normal of IgG, IgA, IgM, C1q and C9 in capillary walls. EM identified deposits in sub-endothelial, 25~35 sec), fibrinogen 583 mg/dL (200~400 mg/dL), antithrombinIII 57% (80~120%), membranous and sub-epithelial sites. protein C 133% (70~140%), protein S 119% (65~140%), D-dimer 18.24 ug/ml (<0.4 ug/ml). On urinalysis, albumin was 4+. Extensive thrombus was found in superior sagittal Neither child remitted on high-dose steroid plus mycophenolate, and anti-C1q antibodies sinus and right transverse sinus on brain MRI. After heparin infusion, nausea and chest (C1q-ab) persisted in spite of treatment. Case 1 showed a decline in GFR at two years, and a tightness developed, so warfarin and low dose aspirin were administered for follow-up biopsy indicated disease progression. Rituximab 750mg/m2BSA was added on 2 anticoagulation. Kidney biopsy could not be performed. Cyclosporine was administered occasions 2 weeks apart, but after 3 months C1q-ab persisted. No other autoantibodies have with slow steroid tapering. His headache improved 2 weeks later and proteinuria emerged. disappeared 1 month later. Two months later, the majority of thrombus disappeared on brain MRI and he is still in remission state of nephrotic syndrome during follow-up period. Given the predictive value of C1q-ab for nephritis in SLE, and the “full house” Conclusion: Extensive cerebral thrombosis in a child with steroid-resistant nephrotic immunohistochemical findings that closely resemble lupus nephritis, we propose that there syndrome was successfully treated with warfarin and aspirin which was accompanied by may a distinctive pattern of glomerulonephritis associated with isolated anti-C1q-ab. remission of nephrotic syndrome by cyclosporine. Pediatr Nephrol (2006) 21:1493–1635 1615

COD. PP 373 COD. PP 374 ACUTE POST-STREPTOCOCCAL GLOMERULONEPHRITIS AND SURVEY OF THE GEORGIAN REGISTRY OF RENAL BIOPSIES ACUTE EBSTEIN-BARR VIRUS GENOME-POSITIVE (1996-2005) TUBULOINTERSTITIAL NEPHRITIS I Rtskhiladse L Zangurashvili N Abramishvili R Waldher r M Subat-Dezulovic (1), N Sindicic (1), S Flajsman-Raspor (1), G Djordjevic (2), N Brncic Children’s Healthcare Centre Mrcheveli , Br. Subalashvili str. 44 , 0108 Tbilisi , Geor gia (3) (1) Clinical Medical center Rijeka, Dept of Pediatiatric Nephrology (2) Clinical Medical center Rijeka, Dept of Pathology (3) Clinical Medical center Rijeka, dept of Infective The renal biopsy registry of the Georgian Paediatric Nephrology Association has obtained diseases Presenting Author: M Subat-Dezulovic data from 273 patients with biopsy-proven renal diseases between 1996 and December 2005 Clinical Medical Center Rijeka , Children`s Hospital, Dept of Pediatric nephrology , +385 (all renal biopsies done in the country in this time) including clinical data: age 5-75 y (mean RIJEKA , Croatia Croatia 34.7), sex M 127 (56%), F 98 (44%). Renal biopsies from children (<15 year) (n=25; 9%) and transplanted patients (n=20; 7%) are included. Results were classified according to the Renal involvement in infectious mononucleosis caused by Ebstein-Barr virus (EBV) is WHO classification of glomerulopathies (Churg et al. 1995). All morphological analyses infrequent and even less reported simmultaneusly with postreptococcal glomerulonephritis were performed in one centre (Prof. Waldherr, Heidelberg, Germany). (PSGN). We report an 11-year-old boy who presented with clinical signs of infective The pattern of biopsy-proven glomerulopathies in 273 patients was distributed as following: mononucleosis and acute nephritic syndrome manifested by gross hematuria, hypertension primary glomerulopathies (73.1%), glomerulopathies in metabolic diseases (6.8%), and mild renal failure. In addition to fever, tonsillitis, lymphadenopathy, hepatomegalia an d secondary glomerulopathies in systemic diseases (5.7%) and glomerulopathies in vascular atypical lymphocytosis, his viral serology tests were indicative of acute EBV infection. In diseases (4.9%). 7.3% were biopsies from transplanted kidneys, other glomerulopathies the same time, documented streptococcal etiology with law C3 was more convincing cause (1.9%) and 9 unclassified cases. Inadequate material was obtained in 1.5% of cases. Among of renal damage. Renal biopsy revealed diffuse proliferative glomerulonephritis with the primary glomerulopathies diffuse glomerulonephritis (GN) was the most frequent mesangium deposits and subepithelial electron-dence deposits supporting the diagnosis of (54.8%), followed by focal-segmental GN (31%) and minimal change disease (11.7%). The PSGN. Less pronounced was acute tubulointerstitial nephritis with mononuclear cell group of metabolic glomerulopathies was mainly composed of patients with amyloidosis infiltrations that happened to be immunohistochemicaly positive with T lymphocyte marker (83.3%). In the group of vascular disease patients suffered from benign nephrosclerosis CD45RD. The presence of EBV in mononuclear cells was finely confirmed by polymerase (56.3%) and the thrombotic microangiopathies (31.3%). In the group of diffuse GN, chain reaction (PCR) and Southern blot technical specific marker for EBV. The proliferative GN (57%) was the most common, followed by membranous GN (40.2%) and simultaneous occurrence of PSGN and EBV-genome-positive tubulointerstital nephritis to sclerosing GN (2.8%). The pattern of diffuse proliferative GN was further subclassified: our knowledge has not been previously reported. The prompt recovery and uneventful mesangiocapillary GN (34,4%), crescentic GN (31.3.%), endocapillary proliferative GN follow-up for more than three years indicates favorable prognosis, although chronic active (25%) and mesangial-proliferative GN (9.4%). EBV infection could not be excluded with certainty and warrants further surveillance.

COD. PP 375 COD. PP 376 A case of steroid-dependent nephrotic syndrome treated with NEPHRON NUMBER IN PATIEN TS WITH MINIMAL CHANGE rituximab. NEPHROTIC SYNDROME (MCNS) AND FOCAL SEGMENTAL 1 A Dallocchio 2 F Trimoreau 3 J Feuillard 4 V Guigonis 1 and 4 Department of pediatrics, GLOMERULOSCLEROSIS (FSGS) CHU Dupuytren, Limoges, France 2 and 3 Department of biological hematology, CHU KH Kim*1, HW Park2, SJ Hong3 1. NHIC Ilsan Hospital, Department of Pediatrics 2. Dupuytren, Limoges, France Pochon CHA University, Department of Pediatrics 3. Konkuk University, Department of CHU Dupuytren , Department of pediatrics, 8 Ave Martin Luther King , 87000 Limoges , Pediatrics * Presenting Author France NHIC Ilsan Hospital , 1232 Baeksok-dong, Ilsan-gu , 411-719 Koyang-shi , Kyonggi-do South Korea Introduction: High level steroid dependent nephrotic syndromes (SDNS) are sometimes difficult to deal with since toxicity of conventional treatments may limit the therapeutic It has been proposed that a decreased nephron number may be associated with the increased approach. We present here an idiopathic nephrotic syndrome successfully treated with risk of glomerulosclerosis. rituximab. Case: A 7-years-old girl has been treated for a steroid-dependent nephrotic In order to test the hypothesis that a reduced number and increased volume of glomeruli syndrome since the age of three. Relapse of proteinuria occurred despite an oral contribute to the pathogenesis of focal segmental glomerulosclerosis (FSGS), we compared cyclophosphamide treatment. A leg bone pain syndrome led to switch from ciclosporin to the number and volume of glomeruli in 9 patients with FSGS and 8 with minimal change tacrolimus. Tacrolimus allowed withdrawal of corticosteroids and led to a 18-months period nephrotic syndrome (MCNS). without relapses. Relapse occurred during tacrolimus tapering attempt. Then the disease Mean glomerular volume was measured using the method of Weibel and Gomez. An turned out to a high-level steroid-dependent nephrotic syndrome since 60mg/m²/d of estimate of glomerular number (index) was obtained by multiplying the cortical volume of a prednisone associated with 0.2 mg/kg/d of tacrolimus (through level 18µg/L) were kidney by the fraction of renal cortex made up of glomeruli and dividing this by the mean necessary to maintain remission of proteinuria. Mycophenolate mofetil did not lead to any glomerular volume for that kidney x 106 (J Am Soc Nephrol. 5:1659-68, 1995). We improvement. Rituximab treatment was then started. Only three 375mg/m² injections were determined kidney volume from ultrasonic measurement. performed as CD19 lymphocyte had disappeared after the third injection. The other Patients with FSGS had significantly greater glomerular volume than patients with MCNS immunosuppressive treatments were then progressively tapered off without proteinuria [2.02 ± 0.36 (x106 mm3) vs. 1.57 ± 0.27 (x106 mm3)]. But there was no significant relapses. CD19 lymphocytes had remained undetectable for 6 months after Rituximab difference in the Index of glomerular number (estimated glomerular number) between treatment. Twelve months after the onset of rituximab therapy, prednisone was withdrawn FSGS & MCNS patients (2.8 ± 1.4 vs. 3.0 ± 0.8). and tacrolimus was tapered off to 0.09 mg/kg (through level 5.2 µg/L). Adverse effects In summary, the glomerular volume was greater in FSGS patients than MCNS patients. But were: transitory neutropenia following the third injection of rituximab and pneumocystosis there was no significant difference in the Index of glomerular number. despite pentamidine prophylaxis. Conclusion According to the two other published cases, this case suggests that rituximab may be an effective treatment for steroid dependent nephrotic syndrome. Such cases highlight the possible implication of B lymphocytes in the pathogenesis of SDNS. 1616 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 377 COD. PP 378 The characteristics of focal segmental glomerulosclerosis in Egyptian A case of steroid-dependent nephrotic syndrome treated with rituximab Children: Single center study. A Dallocchio F Trimoreau J Feuillard V Guigonis ahmed el-refaey, Ashraf Bakr, Amr Sarhan, Ayman Hammad, Mohamed Ragab,Atef El- CHU Dupuytren , Pediatric Department , 87000 Limoges , France Mogy , mansoura university children`s hospital , 35516 mansoura , dakahlia Egypt Introduction: High level steroid dependent nephrotic syndromes (SDNS) are sometimes difficult to manage since toxicity of conventional treatments may limit the therapeutic To highlight the characteristics of Egyptian children with focal segmental approach. We present here an idiopathic nephrotic syndrome successfully treated with glomerulosclerosis (FSGS) who were followed in the Nephrology Division, Mansoura rituximab. Case: A 7-years-old girl has been treated for a steroid-dependent nephrotic University Children`s hospital, the records of 34 biopsy proven FSGS patients (25 males syndrome since the age of three. Relapse of proteinuria occurred despite an oral and 9 females, aged 6.7 ± 4.8 years) were retrospectively analyzed. All patients were cyclophosphamide treatment. A leg bone pain syndrome led to switch from ciclosporin to presented with nephrotic syndrome, two patients (5.9%) presented with gross hematuria, tacrolimus. Tacrolimus allowed withdrawal of corticosteroids and led to a 18-months period five patients (14.7%) were hypertensive and five patients (14.7%) had renal impairment. without relapses. Relapse occurred during tacrolimus tapering attempt. Then the disease Family history of FSGS was present in 5% of our patients. All our patients had none turned out to a high-level steroid-dependent nephrotic syndrome since 60mg/m²/d of otherwise specified type of FSGS. All our series patients were steroid resistant, 64.7 % prednisone associated with 0.2 mg/kg/d of tacrolimus (through level 18µg/L) were initial resistant and 29.4 % late resistant. The Mendosa protocol was given as a main necessary to maintain remission of proteinuria. Mycophenolate mofetil did not lead to any protocol of therapy in 85 % of our patients out of them13 patients (44.8%) were responders, improvement. Rituximab treatment was then started. Only three 375mg/m² injections were 16 patients (55.2%) were resistant. At last observation, 38.3% of the cases were in performed as CD19 lymphocyte had disappeared after the third injection. The other remission, 7% on dialysis, 6% died and 48% of them lost follow up. immunosuppressive treatments were then progressively tapered off without proteinuria relapses. CD19 lymphocytes had remained undetectable for 6 months after Rituximab treatment. Twelve months after the onset of rituximab therapy, prednisone was withdrawn and tacrolimus was tapered off to 0.09 mg/kg (through level 5.2 µg/L). Adverse effects were: transitory neutropenia following the third injection of rituximab and pneumocystosis despite pentamidine prophylaxis. Conclusion According to the only two other published cases, this case suggests that rituximab may be an effective treatment for steroid dependant nephrotic syndrome. Such cases highlight the possible implication of B lymphocytes in the pathogenesis of SDNS.

COD. PP 379 COD. PP 380 Long-term outcome of cyclosporine A and cyclophosphamide treatment Combined occurrence of organic aciduria, spinal muscular atrophy and in childhood nephrotic syndrome diffuse mesangial sclerosis. Coincidence or a new disease entity? V Sümegi, I Haszon, Cs Bereczki, S Túri Gy Tálosi1, K Rácz1, I Németh2, L Kaizer2, E Karg1, S Túri1. Departments of 1Paediatrics , University of Szeged, Department of Pediatrics, Korányi fasor 14-15 , H-6720 Szeged , and 2Pathology, University of Szeged, Szeged, Hungary. Hungary Department of Paediatrics, University of Szeged. , Korányi fasor 14-15. , H-6725 Szeged , Hungary A retrospective study was made on 37 children with idiopathic nephrotic syndrome (INS) who were admitted between 1989 and 2000 (follow-up time 5-13 years, median 7.1 years). Mesangial sclerosis may cause uraemic condition and nephrotic symptoms in infancy. Our 15 children (7 FSGS, 5 MCNS, 3 IgMNP) were selected in group I and received aim is to present our case, who had a combined illness of three rare diseases. cyclosporine A (CSA). The infant was first admitted shortly after birth. She was delivered at home, as a 10th living Group II consisted of 22 children (3 FSGS, 10 MCNS, 9 IgMNP) who received child from the 11th pregnancy of the mother. On arrival she was expressly hypotonic, with cyclophosphamide (CP). At the start of NS we followed the ISKDC recommendations. All repeated hypoglycaemic periods, although certain history of perinatal hypoxia was not patients received more than one steroid course; (median: 4). The duration of CSA treatment known. Mass tandem spectrometry showed elevation in the C4-acylcarnitine region, raising was 28±15 months. CP was introduced orally for 2.5±0.5 months. the likelihood of short chain acyl-carnitine dehydrogenase or isobutyril CoA dehydrogenase In the CSA group, the level of proteinuria decreased significantly from 3.98±2.35 g/day defect. Renal function tests were normal. At the age of 1 month she was sent to a country (X±SD) to 0.88±1.4 g/day; in the CP group from 3.9±2.9 to 0.55±1.4 g/day (p<0.001). hospital nearby her living place, further metabolic examinations were planned. The relapse-free period after the end of the therapy was longer in the CP group (p<0.001). One month later the child was referred with a septic shock condition. She became oligo- At the end of the 5 year follow-up 10/15 patients (66.6%) were in remission in the CSA anuric and we lost her in a multi-organ failure. Pathohistological examination of the kidneys group, with or without treatment. In the CP-treated group, 20/22 patients (90.9%) were in revealed typical signs of diffuse mesangial sclerosis, resembling the picture of wt-1 gene the same condition (p<0.05). The blood pressure and the creatinine clearance level were not mutation, while the musculature and spinal cord pathohistology found spinal muscular significantly different between the two groups after the five year follow-up. atrophy. Nevertheless, the relapse rate was lower and the relapse free period was longer in the CP It is very unlikely, that two or even more rare diseases would occur together. We did no t treated group, in the long term, both CP and CSA seem to be advantageous choice found literature connections between any two of the three diseases present in this case. following the steroid monotherapy of INS patients. Pediatr Nephrol (2006) 21:1493–1635 1617

COD. PP 381 COD. PP 382 Pharmacokinetics of cyclosporine and therapeutic efficacy in children THERAPEUTIC DRUG MONITORING (TDM) OF with idiopathic nephritic syndrome MYCOPHENOLATE-MOFETIL (MMF) AND MYCOPHENOLATE Masashi Morooka, Kayoko Umemura, Nihoko Ito, Yasuto Yamamoto and Yoshizo Asano SODIC (CS-MPS) IN CHILDREN WITH CORTICO-DEPENDENT Fujita Health University School of Medicine , Department of Pediatrics, , 4701192 NEPHROTIC SYNDROME (CDNS) AND LUPUS NEPHRITIS (LN) Toyoake , Aichi Japan M. Caropreso, F Nuzzi, G Malgieri, M D`Armiento, R Indaco, M Gallo, A De Rosa, V Bisesti, MM Balletta, C Pecoraro Department of NephroUrology, Santobono Background: Cyclosporine (CsA) has been used in frequently relapsing (FR) idiopathic Children`Hospital, Naples, Italy neprotic syndrome (NS). But the relationship between the concentration and the efficacy in Santobono Children`s Hospital , Department of NephroUrology, via Mario Fiore n°6 , children with NS is still unclear. We studied the relationship between phamacokinetics (PK) 80129 Naples , Italy and therapeutic efficacy of CsA. Material and methods: Sixteen patients (mean age 9.6, M:F 9:7) with steroid dependent and We studied the TDM of MMF in 35 children (M19, mean age 11.2y,3.1-18) with cortico- FRNS (12 MCNSs and 4 FSGSs) were entered into this study. They all took microemulsion dependent nephrotic syndrome (CDNS) and 12(3M, mean age 16.4,5.6-18.9) with LN and formulation of CsA (2.3~5.9mg/kg/day) devised twice a day before the meal. We assayed CS-MPS in 10 children (5M, mean age 6.3, 3.5-11.6) with CDNS and 3 girls with LN concentrations of CsA and estimated the PK parameters using concentration time profiles (mean age 18.1, 15,6-20.2). Mean dose of MMF and CS-MPS was 29mg/kg/day and by moment analysis. We devised these patients into two groups with estimated Cmax over 24mg/kg/day, respectively; mean value of through level was 2.4 ìg (0.9-4.2). All patients than 600ng/ml (group A) and less than 500ng/ml (group B), and compared the number of received steroids before MMF/CS-MPS. Until now TDM of these drugs was studied only in relapse and the amount of prednisolone (PSL) between before and after starting CsA. transplanted patients where concomitant antirejection drugs intefere with MPA clearance. Results: The mean values of estimated Cmax were as follows, group A; 882.2 ng/ml, group Our study population may represent a pure model, because most patients received just B; 298.8 ng/ml. Only group A showed statistically significant reductions in both the numbe r MMF, 18(31.5%) received also Prednisone. After oral administration, mean bioavailability of relapse (pre;2.4/year, post; 0.6/year) and the amount of PSL (pre; 0.66mg/kg/month, is 90% with mean Tmax: 56min (15-70) for MMF and 250min.(80-270) for EC-MPS. post; 0.22mg/kg/month). Group B also showed these reductions, but they were not Corticosteroids interfere on AUC, not on Tmax. We could evaluate the TDM of both drugs statistically significant. in the same subject. In 2 children with CDNS and 2 with LN, MMF was shifted to EC-MPS Discussion and Conclusion: From our data, higher concentration of CsA showed better because of gastrointestinal side effects. TDM of EC-MPS showed us that EC- therapeutic effectiveness in children with FRNS, so we should set Cmax over than MPS,administered on empty stomach hits max concentration after 2 hours with same AUC 600ng/ml. Furthermore, we need to conduct further investigations because of small sample of MMF. Moreover, on EC-MPS therapy gastrointestinal symptoms disappeared allowing size and add the analysis of side effects such as tubular interstitial damages due to high us to stop gastroprotective drugs. Our experience suggests that, in children with CDSN and concentration of CsA. LN treated with MMF or EC-MPS, TDM is useful to avoid risks related to small range between lack of efficacy and toxicity, to detect non-compliant patients and to standardize dose regimens in small children with their relatively larger volume and faster hepatic metabolism.

COD. PP 383 COD. PP 384 Membranoproliferative glomerulonephritis (MPGN) with C3 Epidemiology of Nephrotic Syndrome deposits,C3 nephritic factor ( C3NeF) and heterozygous factor H (FH) P Geier (1), Z Dolezel (2), J Starha (2), H Tomaskova (3), A Kudlickova (4) Dept of or factor I (FI) mutations. Pediatrics, Teaching Hospital, Palacky University, Olomouc,(1) Dept of Pediatrics, MA.Macher1,V.Baudouin1, V.Frémeaux-Bacchi2, MA.Dragon-Durey2, M.Peuchmaur3, Childrens Hospital, Masaryk University, Brno,(2) Dept of Pediatrics, Municipality Hospital C.Loirat1 1.Service de néphrologie Hôpital Robert Debré, Paris, 2. Laboratoire Ostrava (3) Dept of Pediatrics, Municipality Hospital Hodonin (4), Czech Republic d’Immunologie Biologique Hôpital Européen Georges Pompidou, Paris, 3.Laboratoire Teaching Hospital , Dept of Pediatrics, I.P.Pavlova 6, , 772 00 OLOMOUC , Czech d’Anatomo-pathologie Hôpital Robert Debré, Paris, France. Republic Hopital Robert Debre , Service de nephrologie, 48 Bd Serurier , 75935 cedx 19 Paris , France Background: Nephrotic syndrome (NS) is a rare disease with incidence between 2 - 7/100 000 children. In the last 10 years there are some reports about increasing incidence of FSGS The association of C3NeF with MPGN type I or II is well established. C3NeF, an Ig among the nephrotic children and most of them are from North America. There are only a autoantibody, prolongs the enzymatic half-life of C3 convertase (C3bBb), producing few epidemiologic data from Europe. continuous C3 activation. Methods:A working group of pediatricians and pediatric nephrologists who treat children We report 2 children who developed MPGN with C3 deposits in association with C3NeF with NS was created in four regions of Czech Republic. NS, remission, relaps, and heterozygous mutations in FH (1 case) and FI (1 case) genes. steroidresistance, steroiddependence was defined according ISKDC. All patients were Case 1. This 30 months-old boy presented with recurrent macroscopic hematuria (HU) and treated uniformly in concordance with Evidence-based guidelines (6+6 regimen). A proteinuria (PU)( 1 to 4 g/l) without nephrotic syndrome (NS) since age 2. Renal biopsy questionaires which contained basic data concerning the course of the disease were filled (RB) showed MPGN type II with mesangial hypercellularity and thickening of capillary out and collected at one centre. Analysis of questionaires provided basic epidemiological walls with C3 deposits with atypical presence of humps. data. There were 791 564 children living in this region in 2004. Case 2. This 13 years- old boy was referred for recently diagnosed NS but edema since 2 y. Results: 28 patiens with NS were newly diagnosed in the time period from January 1st, RB demonstrated MPGN type I with sub- endothelial C3 deposits. 2004 until December 31st, 2005. Incidence of NS is 1,75 / 100 000 children. 14,3% of complement charasteristics of patients: see table patiens were corticoresistant, 30.7% were corticodependent and 53.8% with occasional relapses. Incidence of steroidresistant NS is 0,25/100 000. As alternative treatment was given cyclophosphamide in 30.7% and/or cyclosporine A in 17.8%. These case reports show that deficiencies in FH or FI, 2 major regulatory proteins of All 4 patients with corticoresistant NS underwent percutaneous renal biopsy. Histological complement alternative pathway, have a role in the pathogenesis of MPGN with C3NeF. findings were as follows: 1x FSGS, 1x difuse mesangial proliferation, 1x C1q nephropathy The association of homozygous FH deficiency with MPGN and various types of GN (other and 1x membranous nephropathy. that hemolytic uremic syndrome) has been reported in 8 and 7 cases respectively. But the Conclusion: The incidence of NS is comparable with other reports from Europe. The association of MPGN with heterozygous FH or FI mutations had not been reported until yet. incidence of steroidresistant NS is low and the same as reported in UK in the 90th. 1618 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 385 COD. PP 386 Allergy, CD23+CD19+ and CD25+CD4+ Lymphocyte Subsets and Polymorphic marker R229Q in children with nephritic syndrome Nephrotic syndrome EK Petrosyan, A N Tzygin, A E Shestakov Yildiz B, Kural N, Ayata M, Gulbas Z Russion Medical University , Lipechkaja str.14-203 , 115404 Moscow , Russia Eskisehir Osmangazi University, Department of Pediatric Nephrology , Meselik , 26480 Eskisehir , Turkey We investigated polymorphic marker R229Q (G755A), at children with nephrotic syndrome (NS). Among researched patients from with minimal change nephrotic syndrome (MCNS) Steroid responsive minimal change nephrotic syndrome (SS-MCNS) is the most common was 58, with focal-segmental glomerulosclerosis ãëîìåðóëîñêëåðîçîì (FSGS) 21 and 39 form of nephrotic syndrome in childhood and it has been recognized association with children with mezangioprolypherative glomerulonephritis (MPGN) . The control group has allergic disease. However, immunogical mechanisms of this association unclear. Aim of the consisted from 80 person without disease of kidneys. Polymorphic marker R229Q it was present study, to understand of immune response during active nephrotic phase (ANP: stud-ied with help PCR of a method. As a result of research by us the following urinary protein >40 mg/m2 per hour, serum albumin <2.0 g/dl) and remission stage (RS) in distributions of genotypes are received: at patients from NS- GG-85,6 of % GA-14,4 of %, SS-MCNS. We were analyzed lymphocyte subsets (CD3, CD4, CD8, CD19, in control group GG-95,5 of % GA-4,5 of % (2=4,9 p <0,05). However the greatest CD23+CD19+, CD25+CD4+) and immunoglobulins (Ig) in different stages of the SS- frequency of genotype GA - 25,64 % were marked at patients with MPGN in comparison MCNS and atopic SS-MCNS before corticosteroid treatment. A total of 25 patients with with other forms glomeru-lonephritis:MCNS-GA-8,62 %; FSGS-GA-16,6 % (2=10,76 p SS-MCNS (13 (52%) of 25 patients with RS and 12 (48%) of 25 patients with ANP) and 25 <0,001)). We speculate, that high association of genotype GA with MPGN, defines healthy children were recruited for studies. Of the 15 (60%) patients had a history of atopy. development in NS in structure of the given morphological form. The serum IgE levels (U/ml) in ANP were significantly higher than remission and control subjects (540,9±248,9/112,4±34,4 and p<0,05; 540,9±248,9/15±3,1 and p<0.05, respectively). The percentage of CD3, CD4, CD8 and CD19 cells did not differ between patients with ANP and RS. The percentage of CD23+CD19+ cells were increased in ANP compared to RS (15,8±3,9/8,5±0,5%, p<0.05) and controls (15,8±3,9/6,5±1,2%, p<0.01). Also, CD23+CD19+ cells were increased in patients with atopy than without atopy (14,3±2,7/8,3±0,4%, p<0,05). The percentage of CD25+CD4+ cells did not differ between patients with ANP and remission and control subjects (p>0,05). These data suggests patients with SS-MCNS have abnormalities of CD23+CD19+ cells and we think that therapy of regulatory T cells analogous may prevent of ANP in SS-MCNS in fiture.

COD. PP 387 COD. PP 388 Treatment and Outcome of Pediatric Patients with Primary Focal CHANGES IN SERUM LIPOPROTEIN (a) LEVELS IN CHILDREN Segmental Glomerulosclerosis WITH MINIMAL CHANGE NEPHROTIC SYNDROME DURING Yavaþcan Ö, Sözeri BY, Mutlubaþ F, Kabasakal C, Mir S, Department of Pediatric ALBUMIN-FUROSEMID AND PREDNISONE TREATMENT Nephrology, Ege University, Faculty of Medicine, Izmir, Turkey. S Tugay, Z Bircan Izmir Tepecik Teaching Hospital Department of Pediatric Nephrology , Izmir Tepeci k Kocaeli University , Kocaeli University Faculty of Medicine Pediatric Nephrology Teaching Hospital Department of Pediatric Nephrology , 35100 Izmir , Turkey Department Umuttepe , 41380 Kocaeli , Turkey

Idiopathic focal segmental glomerulosclerosis (FSGS) is one of the leading causes of end It has been known that serum lipoprotein (a) (Lp (a)) has been increased in nephrotic stage renal disease (ESRD) in childhood nephrotic syndrome. The aim of this retrospective syndrome. In this study Lp (a) levels and the relation between Lp (a) and other lipid study is to demonstrate treatment, and outcome of patients with FSGS. parameters were analyzed during albumin-furosemide and prednisone treatment The patient population consisted of 38 children ranging in age at disease onset from 12 to Eleven children with severe nephrotic edema (6 girls, 5 boys) with minimal change 186 months (average: 68.351.5 months). The patient population included 25 boys (65.7%) nephrotic syndrome (MCNS) were studied. Lp (a), cholesterol, triglyceride, LDL, VLDL, and 13 girls (34.3%). Patients evaluated at their last visits after 49.2±44.9 months (6173 HDL, albumin were recorded during both albumin-furosemide and prednisone treatment. patient months). We examined records of patients with FSGS for information on baseline All parameters were measured before, 2 and 24 hours after albumin-(%20 albumin solution, clinical parameters, morphological parameters on biopsy, age, gender, treatment regimens 0.5 g/kg infused for one hour), furosemide (2mg/kg , IV 30 min. after albumin infusion) and and outcomes. Podocin mutation (PM) was investigated in 14 patients. Prednisolone also before the beginning of prednisone, on the day of beginning of diuresis and on the 3rd treatment was the first choice for all patients, but 25 patients needed additive treatments day of remission. Statistical analysis was performed by Pearson and Wilcoxon tests (P which consist of prolonged steroid treatment, oral cyclosporine or cyclophosphamide. <0.005). Nephrotic syndrome was most frequently presentation (92.1%). On biopsy, sclerosis was Decrease of Lp(a) (74.30±80.12, 53.49±52.13 mg/dl) and LDL (266.18±89.10, found in 20 patients (53.6%). While, among these patients ESRD, non-remission and 217.36±62.36 mg/dl) were recorded as statistically significant at the 2nd hour of albumine- remission were observed 26.6%, 60%, 13.3%, patients without sclerosis these ratios were furosemide treatment. On the day of diuresis during prednisone treatment increase of observed 33.7%, 7.6%, 61.5% in follow-up respectively (p<0.05). In 12 patients was cholesterol, LDL, HDL, VLDL were recorded as statistically significant together with detected to PM and 9 patients with PM have developed ESRD in follow-up. increase of albumin, but unchanged Lp(a) (p>0.050). On the day of remission only Lp(a) FSGS is a heterogeneous disease and most patients progress to ESRD. In these patients (48,02±49,59 mg/dl) levels were in the normal interval together with albumin. should be surely investigated PM. However, the sclerosis on early biopsy is important for It was concluded that Lp(a) is the only lipid parameter which affected from albumin progression ESRD. The overall high risk of ESRD with FSGS serves to emphasize the need infusion and also it is also the first improved lipid parameter during remission. for alternative treatments. Pediatr Nephrol (2006) 21:1493–1635 1619

COD. PP 389 COD. PP 390 STEROID SENSITIVE NEPHROTIC SYNDROME and ATOPY Two Cases with Transitory Minimal Change Disease to Focal Segmental R Topaloglu(1),E Varol(1),B Sekerel(2),H Canpinar(3),D Guc(3),N Besbas(1),S Ozen(1),A Glomerulosclerosis Bakkaloglu(1) 1Pediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara, PK Kim, JH Song, JS Song* Departments of Pediatrics & Pathology*, Kwandong Turkey 2Pediatric Allergy, Hacettepe University faculty of Medicine, Ankara, Turkey University College of Medicine, Koyang, Korea 3Basic Oncology, Hacettepe University Institute of Oncology, Ankara, Turkey , Hwajung-dong Myongji Hospital Dept. of Pediatrics , 697-24 Dukyang-ku , Koyang South Hacettepe University faculty of Medicine , Department of Pediatric Nephrology , 06100 Korea Ankara , Turkey Background Minimal change disease(MCD) is the most common pathological entity We aimed to define the association with atopy and steroid sensitive nephrotic syndrome underlying nephrotic syndrome in the pediatric population and usually having good (SSNS). prognosis. But focal segmental glomerulosclerosis(FSGS) progress frequently, and leads to Thirty children with SSNS (15 in relapse 15 in remission) 12 atopic patients and 12 health end-stage renal failure in most patients. It has been proven by repeated renal biopsies that controls were enrolled the study. Demographic characteristics and history of atopy were some patients with apparent MCD at the initial biopsy, progress to FSGS. We experienced defined. Blood total eosinophil count, serum total and specific IgE levels were measured. two cases of MCD at initial renal biopsy who progressed to FSGS. Serum soluble IgE receptor (sCD23) were quantified with human sCD23 ELISA kit and Clinical Case (case1) A 4-year-old girl was admitted because of gross hematuria. percentage of mononuclear cells producing IL-4 and IL-13 which are regulatory cytokines Proteinuria was not improved for 6 weeks and renal biopsy was performed. The pathologic of IgE synthesis were measured with flow cytometry. Skin prick tests were performed in all finding suggested MCD. Three years later, a second renal biopsy was performed, because patients. microscipic hematuria and proteinuria(1002 mg/day) were noted for past 2 months. There Depending on skin prick tests, specific IgE levels and clinical history atopy was found in was no pathologic change. After another 2 years later, a third renal biopsy was performe d only two of patients. There were no significant differences in total eosinophil counts, serum because of persistent proteinuria(5313 mg/day), and the final pathologic finding suggested IgE levels and percentage of IL-4 producing cells between relapse, remission, atopy and FSGS. control groups. Although serum total IgE levels were higher in atopy and relapse groups (case 2) A 5-year-old boy was admitted because of periorbital swelling for 3 days. Despite these differences did not reach the statistical significance. The percentage of mononuclear of corticosteroid therapy for 6 weeks, proteinuria(4220 mg/day) was not improved. Renal cells producing IL-13 was significantly high in relapse group compared with control group biopsy was performed and the pathologic finding suggested MCD. Despite of aggressive (p<0.05). A statistically significant increase was also found in sCD23 levels in relapse steroid and cyclosporine treatment for 2 years, hematuria and proteinuria(8772 mg/day) compared with remission, atopy and control groups (p<0.05). were persisted. Second renal biopsy was performed and the pathologic finding suggested We have found very low number of atopy in our patients with nephrotic syndrome. Our data FSGS. suggest that the elevated serum IgE, sCD23 levels and increase percentage of IL-13 Conclusion Children with MCD who had frequent relapse in spite of corticosteroid therapy, producing cells during relapse may reflect some common immune activation following or no remission should be mentioned with repeated renal biopsy and other therapeutic various stimuli rather than a direct association with atopy. regimen for FSGS.

COD. PP 391 COD. PP 392 A very unusual presentation of IgA nephropathy in a child ENDOTHELIN-1 PLASMA LEVELS IN NEPHROTIC SYNDROME F Ozaltin*1, Y Bilginer1, S Gucer2, A Bakkaloglu1 Hacettepe University Faculty of T Margieva, T Sergeeva, A Ts ygin , Research Centre for Child Health, Moscow Medicine, Dept.of Pediatrics, Units of Nephrology1 and Pathology2 Research Centre for Child Health , Pediatric Nephrology, Lomonosovsky pr. 2/62 , 119991 , Hacettepe University Faculty of Medicine Dept.of Pediatric Nephrology Sihhiye , 06100 Moscow , Russia Ankara , Turkey Endothelin-1 (ET-1) is a powerful renal and systemic vasoconstrictor with growth- A 10-year-old male was referred to our center due to nephrotic syndrome. His previous and promoting properties. It is derived mainly from endothelial cells and detected as a marker of family histories were uneventful except for a tetanus toxoid vaccination, which had been endothelial dysfunction. It facilitate extracellular matrix accumulation and progression of performed 1 mo ago. There were neither consanguinity between parents nor renal disease in tissue fibrosis, including renal fibrosis. the family. Physical examination showed diffuse edema with normal blood pressure. The aim of our study was to investigate plasma levels of ET-1 in children (n=51, 27 males, Complete blood count and blood chemistry including serum complement profile were 24 females, 5-16 years old) with nephrotic syndrome (NS) and 15 healthy same age within normal limits except for albumin (1.7 g/dl) and cholesterol (394mg/dl). Urinanalysis subjects. 26 patients had a relapse of the disease, others had remission. showed massive proteinuria (12g/24h) and hematuria. Renal ultrasonography demonstrated Plasma levels of ET-1 were measured by ELISA. bilateral minimal renal enlargement and increased echogenicity. An oral prednisone was Results. ET-1 was elevated in relapse of focal segmental glomerulosclerosis (FSGS) and instituted (60mg/m2) for 4 weeks. Diuresis was observed however nephrotic range membranoproliferative GN (MPGN): 2,61±1,05fmol/ml, 3,51±1,77f/mol respectively, proteinuria persisted. Pulse i.v. methyl prednisolone (500mg/day, 3 consecutive days) was p<0,0001 compared with controls (0,6±0,3fmol/ml), minimal change disease administered and alternate day oral prednisone (40mg/m2) was continued. Since no (0,7±0,38fmol/ml) and mesangioproliferative GN (MesPGN) (0,8±0,1fmol/ml). Children remission was observed following steroid therapy, a renal biopsy was performed. IgA who had elevation of arterial blood pressure demonstrated increased levels of plasma ET-1 nephropathy was diagnosed based on light, immunoflorescence and electron microscopic (3,65±1,09fmol/ml, p<0,0001 compared with normotensive subjects). findings. Pozzi’s protocol modified by adding cyclosporine A, enalapril and fish oil for 5 Normal levels of ET-1 was observed in remission in all morphological forms of NS (p>0,05 months were started. At the end of 6 months, blood chemistry including total protein, compared with controls). albumin and lipid levels normalized. However, 1g/24h proteinuria persisted Conclusion. Increased plasma ET-1 levels is likely to contribute to glomerulosclerosis With this patient, we aim to point out that IgA nephropathy could come to medical attention directly by elevation of BP, induction of the formation of extracellular matrix proteins and with nephrotic presentation, which is very unusual for the disease. Since there is no fibronectin or via potentiation of TGF-â effects. consensus how to treat children with IgA nephropathy in the literature, we would like to share our experience in this patient, who presents a very severe course of the disease. 1620 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 393 COD. PP 394 Chlorambucil therapy in children with steroid-resistant nephrotic Pediatric Continuous ambulatory peritoneal dialysis : one centre syndrome. experience JA Kari A Alkushi HO Alshaya Yildiz B, Kural N, Evim M, Kural Y, Hanci S King AbdulAziz University Hospital , Paediatrics , P O Box 80215 Jeddah , Saudi Arabia Eskisehir Osmangazi University, Department of Pediatric Nephrology , Meselik , 26480 Eskisehir , Turkey Background: Chlorambucil (CHL) had been used for treatment of steroid sensitive nephrotic syndrome (SSNS) as steroid sparing agent in those with frequent relapsing or Continuous ambulatory peritoneal dialysis (CAPD) has become a popular form of renal steroid dependent course. However, its use for treating steroid resistant nephrotic syndrome replacement therapy in pediatric patients. Unfortunately despite recent advance in PD (SRNS) is limited to few small studies. It was found to induce complete or partial remission techniques and equipment, complications of CAPD may be potentially life-threatening. In in patients with SRNS caused by either focal segmental glomerulosclerosis (FSGS), this paper, we show our experience of CAPD. A 28 children (13 boys, 15 girls, mean age: mesangiol proliferative glomerulonephritis (MPGN) or minimal change disease (MCD). 12,9±4,3 years) who treated with CAPD were included in this study between February 2002-November 2005. Diagnosis of our children were reflux (40,3%), glomerular disease Methods: A retrospective study was conducted to evaluate the role of CHL in the (35,5%), cystic diseases (11,3%), agenesic/disgenesic kidney (6,2%), vasculitis (3,2%) and management of children with SRNS. Seven patients with SRNS (five patients with IgM metabolic diseases (3,2%). The hemoglobulin and albumin levels were 9,4±1,4 and 3,8±0,8 nephropathy, one with FSGS one with diffuse mesangial hypercellularity (DMH) received g/dl (mean±SD). Serum calcium, phosphorus, alkaline phosphatase and paratyroid hormone 8-12 weeks of CHL. Their mean + SD age at presentation was 4.8 + 2.6 years, median levels were 9,5±1,5 mg/dl, 4,8±1,2 mg/dl, 551,6±435 U/L and 463±644,7 pg/ml (range) 4 (2-9) years. The total accumulative dose (mean + SD) was 10.1 + 3.2 (7.0-15.2) respectively. Measurement of blood urea nitrogen, creatinine (Cr) and Kt/V were showed mg/kg. that CAPD was effective in our patients (49,9±15,5 mg/dl, 7±2,4 mg/dl and 2,2±0,9 respectively). We found a positive correlation between Kt/V and hemoglobulin (r=0,317; Results: Two patients with IgM nephropathy achieved complete and sustained remission. p<0,05) and Kt/V with albumin (r=0,256; p<0,05). Peritonitis was most frequent Both of them received 12 weeks course with total accumulative dose of 15.2 and 14mg/kg. complications of CAPD (20 peritonitis attacks in 28 patients). A 3 (10,7%) of 28 patients One patient with FSGS achieved partial remission with 8 weeks course of CHL therapy. No had fungal peritonitis. Other complications were hypervolemia and hypertension (21,4%), side effects were observed in any of our patients hidrocele/herni (7%), malrotation of catheter (10,7%) and pleuroperitoneal fluid access (3,6%). During the follow-up period, 1 (3,6%) of 28 patient was transferred to hemodialysis Conclusion: CHL therapy in a total accumulative dose of 15 mg/kg and 12 weeks duration and 2 (7,2%) of 28 patients died owing to sepsis and cardiopulmonary complications. In could result in complete remission in children with SRNS secondary to IgM nephropathy. conclusion, CAPD may provide adequate of metabolic control and Kt/V reflects levels of Further randomized controlled studies are required. hemoglobulin and albumin in end stage renal disease.

COD. PP 395 COD. PP 396 The importance of residual renal function in children on chronic Continuous Ambulatory Peritoneal Dialysis in Iranian Children – Multi peritoneal dialysis. central Experiences. CJ Stefanidis, A Mitsioni, V Askiti, E Siomou, D Siapera. 1. N. Hooman –Assistant Professor1 2. A. Madani –Associate Professor 2 3. M. Sharifian – , Thivon and Levadias Str, Goudi , 11527 Athens , Greece Associate Professor 3 4. H. Otoukesh –Associate Professor 1 5. S. T. Esfehani –Associate Professor 2 6. M. Mohkam –Assistant Professor 3 7. P. Mohceni –Assistant Professor 2 8. OBJECTIVE: The aim of this retrospective single-centre study was to analyse the impact of A. Mahdavi – Assistant Professor 1 9. N. Ataii –Associate Professor 2 10.A. Derakhshan – residual renal function (RRF) on outcome of 33 chronic peritoneal dialysis (PD) patients Associate Professor 4 11.MH. Fallahzadeh –Professor 4 12.G H. Al Hashemi –Professor4 (6.3+/-4.5 years of age). 13. M. Basiratnia –Assistant Professor 4 13.F. Golikhani –CAPD Nurse – BC3 14. E. Latif MEASUREMENTS: During a 15 year period we performed 285 measurements of –CAPD Nurse – BC2 1Division of Pediatric Nephrology - Ali Asgar Children Hospital- normalized equivalent of protein nitrogen appearance (nPNA), Kt/V urea, creatinine Iran University of Medical Sciences 2 Division of Pediatric Nephrology – Markaz Tebi clearance (Ccr) in urine and 24-h effluent collection. RRF was calculated as the average of Koudakan– Tehran University of Medical Sciences 3 Division of Pediatric Nephrology – Ccr and urea clearance in 24-h urine. The follow-up period was 95 patient-years. All Mofid Children Hospital – Shahid Beheshti 4University of Medical Sciences– Division of patients had at least three measurements /year. Pediatric Nephrology – Namazee Hospital – Shiraz Uniersity of Medical Sciences RESULTS: At the initiation of PD 23 patien ts had a RRF >1 ml/min/1.73 m2 and 10 were Iran University of Medical sciences , N201 , Ali asgar Children Hospital, Vahid dasgerdi anuric. The two groups did not differ in age, body size and duration of PD (2.8+/-1.3 versus st., Modares Frw. , 34317 TEHRAN , Tehran Iran 3.1+/-2.1 years). The RRF contributed to 46 +/-18% of Ccr at the first month of PD and to 35+/-16% at the end of the follow-up. The reduction rate of RRF was higher in children Objective: To study epidemiology of Iranian children on CAPD. with proteinuria, higher nPNA and history of aminoglycoside administration. Compared with patients with RRF >1 ml/min/1.73 m2, anuric children had lower Ccr (66 Method: The records of children on CAPD were collected from four main dialysis centers +/-12 versus 98 +/- 23 L/week/1.73 m2, p<0.0001), lower Kt/V urea (2.7+/-0.4 versus (Ali Asgar, Markaz Tebi, Mofid, and Namazee Children Hospital). Peritonitis rate, patients 3.3+/-1.0, p=0.0002), lower delta height SDS (p=0.0001), lower values of serum albumin survival were determined. T-student, Chi2, Kaplan mayer were used to compare means, (p=0.008), higher decline of ultrafiltration rate (p=0.0001) and higher rate of PD failure (p = frequency and survival. P<0.05 was considered significant. 0.04, Fisher`s exact test). CONCLUSIONS: RRF is an important contributor to the adequacy parameters and has a Result: Between 1993 and 2004, 67 children (32 females, 35 males) with a mean age of significant effect on nutrition, growth and outcome of children on PD. 32.64 months (range 0.08 – 156) were on CAPD. The etiologies of renal failure were hereditary (30%), cystic (28%), glomerulopathy (25%), and uropathy (16%). 118 Tenckhof f catheters were inserted surgically. The most frequent surgical complications were hernia and leakage. Peritonitis rate was 1:4.85 patients` months. Peritonitis was higher in children <12 months, and lower BMI at start of CAPD ( P= 0.01). The result of peritoneal fluid cultures were gram positive (32%) and gram negative (28%), negative (30%), fungi (10%). There was significant correlation between fungal peritonitis and peritonitis rate and the first episode of peritonitis (P = 0.01). The mean of patient survival was 0.88 year (95% CI 0.61 - 1.16). The outcome of children were recovery ( 9% ) , transplantation ( 7.5% ) , switch to hemodyalisis ( 12% ) , still on CAPD ( 12% ) , and death ( 58%).

Conclusion: We recommend tighter nutritional control, periodical re-education to parents and medical staffs to reduce mortality and morbidity.

Acknowledge: This study was supported by Iran University of Medical Sciences grant No 552. Pediatr Nephrol (2006) 21:1493–1635 1621

COD. PP 397 COD. PP 398 Chronic peritoneal dialysis in infants in Poland Laparoscopic assisted peritoneal dialysis catheter implantation in A Jander1, M Nowicki 1, M Tkaczyk 1, I Makulska 2, D Zwoliñska, J Latoszyñska 3, A paediatric patients Boguszewska-Bàczkowska 3, R Grenda 3, I Baùasz-Chmielewska 4, I Zagoýdýon 4, B M. Castagnetti, E. Verrina, G. Mattioli, A.Trivelli, M. Torre, V. Jasonni, F. Perfumo Leúniewska 4, A Ýurowska 4, E Stefaniak 5, J Zachwieja 5, B Leszczyñska 6, M IG Gaslini Children`s Hospital and Research Institut , Department of Paediatric Surgery - Roszkowska-Blaim 6, K Zachwieja 7, J A Pietrzyk 7, R Wierci ñski 8, W Zoch-Zwierz 8, R Largo G Gaslini,5 , 16147 Genoa , Italy Italy Stankiewicz 9, B Koùùàtaj 10, M Zajàczkowska 10 Presenting Author: M Tkaczyk Nephrology and Dialysis Department Polish Mother’s Memorial Hospital in Ùódê1, Purpose: To assess feasibility and complications of laparoscopic assisted placement of Dialysis and Nephrology Departments in Wrocùaw2, Warszawa3,6, Gdañsk4, Poznañ5, peritoneal dialysis catheters (PDC) in paediatric patients. Kraków7, Biaùystok8, Toruñ9,Lublin10 Materials and Methods: Fifteen patients with a median age of 14,1 (1,4 – 20,5) years Dept. Nephrology and Dialysis, Polish Mother`s Memorial Hospital Research Institute , underwent a laparoscopic assisted PDC insertion. A single 10 mm epigastric port was used 281/289 Rzgowska St , 93-338 Ùódê , Poland unless detection of concomitant diseases at laparoscopic exploration of the abdominal cavity. A double-cuffed straight Tenckhoff catheter was implanted with the deep cuff being Peritoneal dialysis (PD) is a method of choice in renal replacement therapy in small placed within a pre-peritoneal tunnel underneath the left rectus muscle sheath. Catheter tip children with end stage renal disease (esrd) but constitutes various ethical dilemma and was positioned in the left iliac fossa by stylet wire manipulation under laparoscopic control. clinical problem. The aim of the study was to assess the frequency of complications of The exit site was oriented laterally or downward. Subtotal omentectomy was performed via peritoneal dialysis, metabolic disturbances and outcome in children who started chronic the epigastric port site. peritoneal dialysis in infancy. We retrospectively analysed peritoneal dialysis treatment in Results: Median operating time was 55 (30 – 115) minutes. A single port was used in 8 33 children <1 year of age (26 M, 7 F) in the years 1993-2005 in 10 paediatric centres in cases. A right patent processus vaginalis was detected in 1 patient and repaired by open Poland. Results: mean age at the start of dialysis was 4.5±3,5 month (range 2 day to 11 m), surgery. Intra-abdominal adhesyolisis was performed in 2 cases. PD was started in median 6 mean body weight 5.4±2.6kg (range 2.5 to 11 kg), serum creatinine – 3.7±1.5mg/dl, (1 – 15) days after surgery. No early peri-catheter leakages or infectious complications calcium-2.4±1.5mg/dl, phosphate – 6.1±3,1.7mg/dl, haemoglobin – 10.4±2.4g/l. The occurred. Four blockages occurred in 3 patients. One catheter responded to flushing, one peritonitis rate was 1/8.8 patient-month and exit site infection 1/19 patient-month up to age was rescued laparoscopically, and the third was changed two times by a laparoscopic 1 year. The main causes of bacterial peritonitis and exit site infections were St. aureus and assisted technique. St. epidermidis. The mean duration of PD was 6.4±3.9 (<1 year of life) and total 35.5±28 Conclusion: Laparoscopic control allows careful assessment of the abdominal cavity, months. 10 children (30%) required hernia repairs, 12 catheters were replaced, and in 2 recognition and treatment of possible intra-abdominal diseases, and precise placement of cases repositioned. Of the 33 infants 6 died (3 in infancy), 12 underwent renal PDCs minimizing post-operative leaks. Mechanical obstruction remains a common cause of transplantation, in 2 children PD was stopped and 13 (were still dialysed at the date of data early catheter malfunctioning. Laparoscopy can also be useful to rescue blocked catheters. collection. Conclusion: Chronic peritoneal dialysis in infants is connected with high mortality rate, risk of infectious and surgical complications and remained a great challenge for paediatric nephrologists.

COD. PP 399 COD. PP 400 Acute hydrothorax and genital edema in a child with continuous Encapsulating Peritoneal Sclerosis in a Child after Transfer from ambulatory peritoneal dialysis Peritoneal Dialysis to Hemodialysis, who experienced Peritoneal K Bek1, O Özkaya1, E Atalay2, B Dede2 1 Ondokuz May›s University Faculty of Dialysis for 2 Years Medicine, Department of Pediatric Nephrology, Samsun, TURKEY 2 Ondokuz May ›s K H Paik, H Y Lee, S K Lee, D K Jin Department of Pediatrics, Samsung Medical Center, University Faculty of Medicine, Department of Pediatrics, Samsun, TURKEY Sungkyunkwan University School of Medicine, Seoul Ondokuz May›s University Faculty of Medicine , Pediatric Nephrology , 55139 Samsun , Samsung Medical Center, Sungkyunkwan University School of Medicine , Dept. of Turkey Pediatrics, Samsung Medical Center, 50 Ilwon-dong, Kangnam-ku , 135-710 Seoul , South Korea Acute hydrothorax in continuous ambulatory peritoneal dialysis (CAPD) is a rare complication. It is usually right sided and occurs due to peritonopleural defects. Genital Encapsulating Peritoneal sclerosis(EPS) is a clinical syndrome with a high mortality rate edema due to dialysate leakage is also a similar CAPD complication. A 13 years old girl on and is a serious complication of peritoneal dialysis. Rare cases were reported in children CAPD for 2 years with acute hydrothorax and genital edema for two months is persented. and long-term peritoneal dialysis is known to be a risk factor. We reported a child with EPS, She was doing four exchanges daily and hypertonic dialysis did not resolve the symptoms. who experienced peritoneal dialysis for relatively short period(2 years). On last visit because of dyspnea and orthopnea chest X-ray was taken. Cardiomegaly and pleural effusion more perominent on right side were detected. Her blood pressure was Case: A 15-year-old boy with end-stage renal disease presented with abdominal pain. He 130/80 mmHg. Frequent hypertonic dialysis was performed. But no significant decrement had been maintained on peritoneal dialysis(HD) for 2 years and had three episodes of in right sided pleural effusion and genital edema was achieved despite slight resolution of peritonitis(Pseudomonas and coagulase-negative Staphylococcus). He was eventually cardiomegaly. Abdominal X-ray revealed a malpositioned Tenckhoff catheter lower in the transferred to hemodialysis, because of ultrafiltration failure. Within 5 months of transfer to pelvis to which genital edema was attributed. Therefore dialysis was interrupted for 5 days HD, abdominal distension with ascites and ileus developed, which was hemorrhagic upon with catheter removal. Genital and leg edema resolved dramatically and chest X-ray became evaluation. A computed tomography(CT) scan suggested EPS(cystic mass, thickened bowel normal without any other treatment. Previous pulmonary finding was considered as an acute wall and peritoneal calcification), which was confirmed upon laparotomy. The patient was hydrothorax that resolved spontaneously with interruption of CAPD. The CAPD was treated with laparotomy(enterolysis) and prednisolon(1mg/kg/day) for a month. restarted with a new catheter and no edema or hydrothorax were detected in the control roentgenograms taken 15 days later even with CAPD solutions that were not hypertonic. In We report EPS occurred in a child after transfer from PD to HD, who experienced conclusion acute hydrothorax and genital edema are mechanical CAPD complications that peritoneal dialysis for 2 year. Our case shows EPS could occur in children who experienced might be easily confused with hypervolemia and they should be considered in the PD for short period. The possibility of EPS has to be considered in even children regardless differential diagnosis especially when the symptoms are unresponsive to hypertonic of previous PD duration. dialysis. 1622 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 401 COD. PP 402 The effect of enema, in ultrafiltration failure, due to catheter Acute pancreatitis and hemoperitoneum in a continuous ambulatory malposition in children on chronic peritoneal dialysis peritoneal dialysis patient. O. Donmez, N. Cigerdelen, S. Aladag Uludag University, Dept. of Pediatric Nephrology, Y S Hwang1(presenting author), I C Jeong1, J S Lee1, S H Cha2 Department of Pediatrics1, Bursa, Turkey The Institute of Kidney Disease1, Department of Radiology2, Yonsei University, College o f , Uludag University, Faculty of Medicine, Dept. of Pediatric Nephrology , 16059 Bursa , Medicine, Seoul, Korea Turkey Yonsei University College of Medicine , Department of Pediatrics, Yonsei University College of Medicine, 134 Shinchon-Dong, Seodaemun-Ku , 120-752 Seoul , South Korea The aim of this study was to evaluate the effect of enema on ultrafiltration (UF) and to determine whether malpositioned catheter restored or not with emptying enemas. [introduction] Pancreatitis is an uncommon complication in patients on continuous Between June 2004 and December 2005, 37 children with end-stage renal disease were ambulatory peritoneal dialysis(CAPD). The risk factors are as follows: general population dialyzed with chronic PD. Catheter malposition was investigated with abdominal plain film. risk factors, risk factors related to renal insufficiency and risk factors related to the act of Daily urine output and drained dialysate volume were obtained to estimate creatinine peritoneal dialysis. In patients with renal failure, gastrointestinal hormones increase and it clearance (CCr) and Kt/V urea. Patients, with malposition, detected by x-ray, were can cause hypersecretion of pancreatic enzymes that induce pancreatic alteration. Patients performed emptying enema 20 ml/kg per dose every other day with saline. After six doses on CAPD have a higher risk of acute pancreatitis than patients on hemodialysis. UF and localization of the catheter were evaluated. Our patients which have persisted Hemoperitoneum is also well-known complication of dialysis but dialysis is not regarded as malposition were given emptying enema of 14 doses. a direct cause of the bleeding. The average follow-up period was 43.9±27.0 months. During the study, catheter migration [case presentation] A 6 year old boy presented with fever and abdominal pain for 2days. He was determined in 19 patients. In 14 (37.8%) of those patients the UF failure was was diagnosed with ESRD 2 years ago and began CAPD. The cause of ESRD was not determined. Five patients found UF adequacies were excluded the study. There were 4 boys known. The initial laboratory finding showed the following results: WBC 7870/uL, Hb and 10 girls. The mean age was 12.7±4.0 years. Emptying enema was performed to the 14 9.0g/dL, platelet 195000/uL, BUN/Cr 52.1/9.2mg/dL, CRP 6.5mg/dL. Peritoneal fluid had patients who have UF failure. The average dialysate KT/V and CCr values of our patients 4567 WBCs/uL, with 72% polymorphs and 27% monocytes. Candida was grown from the were 2.4±0.7 and 60.5±16.8 L/week/1.73m2, respectively. It was observed that catheter fluid. He was transferred to hemodialysis. During the treatment disseminated intravascular position was restored with enemas in our 11 (78.6%) cases. At the beginning of study, the coagulopathy(DIC) and hemoperitoneum developed. We performed laparotomy, mean UF of our patients was found 667.9±347.9 ml. After enemas, the average UF was adhesiolysis and bandlysis. After operation his condition improved gradually. However he increased to 860.7±336.4 ml. It was seen that UF was increased significantly after enemas complained of a stomachache and the blood chemistry showed amylase 362U/L, lipase (p<0.001). 1056U/L. He went without food for 2 months and then amylase/lipase was checked It was observed that catheter position was restored 78.6% of our patients and UF was 91/96U/L. Radiologic study could’t find any other complication such as pseudocyst. Finally significantly increased. Therefore, we strongly suggest that in patients with UF failure, he received renal transplantation successfully. should be carried out abdominal x-ray and if there is a migration of catheter, enema should perform. [conclusion]When a patient on CAPD shows abdominal pain, pancreatitis and hemoperitoneum should be included as a differential diagnosis.

COD. PP 403 COD. PP 404 ACUTE PERITONEAL DIALYSIS IN CHILDREN WITH A MULTICENTER REPORT ON THE RELATIONSHIP BETWEEN HAEMOLYTIC URAEMIC SYNDROME: A VALUABLE OPTION PERITONEAL CATHETER CHARACTERISTICS AND INCIDENCE GF Laube, JF Falger, EM Rüth, O Bänziger, MJ Kemper, TJ Neuhaus OF PERITONITIS AMONG PEDIATRIC PATIENTS ON CHRONIC Nephrology Unit, University Chhildren`s Hospital Zurich , Steinwiesstrasse 75 , 8032 PERITONEAL DIALYSIS (CPD) Zuerich , Switzerland E Verrina, MG Calevo, F Emma, A Edefonti, B Gianoglio, S Maringhini, C Pecoraro, P Sorino, G Zacchello, G Lavoratti, F Perfumo. on behalf of the Italian Registry of Pediatric Background: Haemolytic uraemic syndrome (HUS) is the most common cause of acute Chronic Dialysis renal failure in children. If renal replacement therapy is required, options are peritoneal G. Gaslini Children`s Hospital , Nephrology and Dialysis Department - Largo G. Gaslini, dialysis (PD), haemodialysis (HD) or hemofiltration (CVVH). 5 , 16148 Genoa , Italy Hypothesis: PD – the treatment of choice in HUS at our institution – is an efficient and safe option in paediatric HUS. We retrospectively reviewed the files of 217 peritoneal catheters placed during 8 years in Methods: Sixty-eight children with HUS (D+HUS: n=52; D-HUS: n=16) with a median age 162 patients with a median age of 6.6 (0.1-17.9) years; median length of follow-up was 8.9 of 2.3 years (range 0.2 – 12) were treated between 1995 and 2005. Tenckhoff-catheter (one (0.2 – 55.1) months. cuff, upward facing) was surgically inserted. Indications for HD or CVVH were life- All catheters were Tenckhoff type (169 with straight and 58 with curled intraperitoneal threatening hyperkalemia, severe colitis, serious general condition or anticipation of segment), and 93% had two cuffs; subcutaneous tunnel shape was straight in 93% of cases plasma-exchange (PEX). (swan neck in 7%), and exit-site (ES) orientation was downward in 57%, lateral in 31% and Results: Fifty-four patients (79%) required dialysis (43 D+HUS; 11 D-HUS). Forty-four upward in 12% of cases. Diagnosis of peritonitis was made when peritoneal effluent was (81%) underwent PD (36 D+HUS; 8 D-HUS). Time span between hospital entry and onset cloudy and its WBC count was > 100/mm3 with > 50% of PMN leukocytes of PD was 4 hours (2–20). Duration of PD was 10 days (1–35). Two patients each were We registered 123 peritonitis episodes with an annualised peritonitis rate of 0.60 and an switched from PD to HD, CVVH or PEX. Technical complications of PD were peritonitis expected time between infections of 19.9 months. (n=9), exit-site infection (n=3) and insufficient ultrafiltration (n=1). Forty-four 44 (85%) Among catheters placed in children in their first 2 years of age (n=68) peritonitis rate was patients with D+HUS recovered; 4 each developed end-stage renal failure or died. Nine higher (0.81 versus 0.50 episodes/year) and peritonitis-free catheter survival rate at 1 year (56%) patients with D-HUS recovered; 4 developed end-stage renal failure and 3 died. The was lower (43.5% versus 71.1%) than among those placed in older patients (P<0.01). running costs of PD were substantially lower compared to HD and CVVD. No statistically significant difference in peritonitis incidence (P=0.59) was found between Conclusions: Acute PD with surgically inserted Tenkhoff-catheter is a safe, efficient an d straight and curled catheters. economic therapeutic option in children with HUS. Peritonitis rate (0.90 episodes/year) and percentage of affected catheters (53.8%) were higher, and one-year peritonitis-free survival rate (46%) was lower for catheters with an upward orientation of ES (P<0.05) than for those with a downward (0.56 episodes/year; 63.4% survival rate; 30.9% of affected catheters) or a laterally (0.56 episodes/year; 68.4% survival rate; 35.3% of affected catheters) oriented ES. In conclusion, these data confirm that younger patient’s age and a downward pointed ES are associated with an increased risk for peritonitis in pediatric CPD patients. Pediatr Nephrol (2006) 21:1493–1635 1623

COD. PP 405 COD. PP 406 HEAT SHOCK PROTEIN (HSP) PROFILE, hsCRPAND LIPID Transmission of Staphylococcus Aureus in Families with Children DISTURBANCES IN CHILDREN ON PERITONEAL DIALYSIS (PD) Undergoing Chronic Peritoneal Dialysis K Musiaù, D Zwoliñska, I Makulska, D Polak-Jonkisz Jun Oh M.D. 1, Heike von Baum M.D2., Elke Wühl M.D. 1, J. Steines1, Günter Klaus Wroclaw Medical University , Dept. of Pediatric Nephrology, M.Sklodowskiej-Curie M.D. 3, Franz Schaefer M.D. 1 and the European Pediatric Peritoneal Dialysis Study Group 50/52 , 50-369 Wroclaw , Poland (EPPS)* 1University Children’s Hospital Heidelberg,Germany 2Department of Medical Microbiology and Hygiene, Ulm University, Germany 3University Children’s Hospital Background: Cardiovascular complications are the main causes of death in ESRD patients. Marburg,Germany Current data suggest the role of inflammation, autoimmunity and lipid disorders in University Childrens Hospital , INF 150 , 69120 Heidelberg , Germany atherosclerosis. Elevated levels of heat shock proteins (hsp), anti-hsp autoantibodies, hsCRP, and lipid disturbances, were described in adults with atherosclerotic lesions. Nasal S.aureus carriership is a major risk factor for catheter-related infections in patients However, there are no investigations on these parameters in children with ESRD, including undergoing chronic peritoneal dialysis (CPD). In children, catheter care is usually those on peritoneal dialysis. The aim of the study was to evaluate the levels of Hsp60, performed by family members. We investigated the prevalence of s.aureus colonization, Hsp70, anti-Hsp60, anti-Hsp70, hsCRP and lipid profile in sera of PD children. Methods: strain sharing among family members and the transmission pathways in children developing Hsp and anti-Hsp concentrations were examined by ELISA in 11 PD patients. hsCRP and s.aureus infections. lipid profile (total cholesterol (CHOL), HDL-C, LDL-C, triglicerides (TGL), CHOL/HDL- Nasal and exit site swabs were obtained from children receiving CPD and their caregivers in C, CHOL/LDL-C, CHOL/TGL, LDL-C/HDL-C ratios) in serum were also estimated. The 163 families in 18 pediatric PD centers. A single colonized subject was identified in 47 control group consisted of 13 healthy age-matched subjects with normal kidney function. families and at least two carriers in 44 families, in 42 of whom genotyping was performed Results: There were no differences in mean values of Hsp70, anti-Hsp60, anti-Hsp70 and using pulsed field gel electrophoresis. In 30 carrier families (71%) 2 or more family hsCRP between examined groups. Hsp60 concentrations in PD patients were decreased vs. members (including 26 patients) shared an identical S.aureus strain. In the group of carrier controls (p<0.01). CHOL, LDL-C and TGL levels in dialyzed children were higher than in families followed prospectively without pharmaceutical intervention, 5 exit site infections the control group (p<0.02; p<0.001; p<0.0001, respectively), whereas HDL-C with S.aureus developed within 5 months. In all cases, the strain infecting the exit site was concentrations in PD patients were significantly lower compared to the control group identical with a nasal colonizing strain previously identified in family members (caregiver (p<0.0001). There was a positive correlation between Hsp60 and Hsp70 (R=0.61, p=0.04) only in 3, caregiver and patient in two cases). We conclude that S.aureus strain sharing is and a negative correlation between Hsp60 and anti-Hsp60 (R=-0.71, p=0.03). However, no common among members of families caring for children treated with CPD, and correlations were found between hsCRP, lipid profile components and other examined transmission of strains carried by the caregivers is the usual route of catheter related parameters. Conclusions: Decreased Hsp60 concentrations in patients on peritoneal dialysis infections in children on CPD. The efficacy of nasal antibiotic prophylaxis or S.aureus may point at the disturbed function of heat shock proteins in PD children. However, lack of vaccination protocols will critically depend on coverage of colonized caregivers. relations between hsp and lipid disorders or hsCRP may suggest that either atherosclerosis progression in ESRD pediatric patients is independent of hsp activity or such connections probably appear in adult life at the earliest.

COD. PP 407 COD. PP 408 CLINICAL OUTCOME OF PEDIATRIC PATIENTS ON Uremic encephalopathy with particular involvement of the basal ganglia PERITONEAL DIALYSIS JM Park, SJ Yoon, JM Oh, JI Shin, JS lEE B Acar, F Yalç ›nkaya, N Çakar, S Yüksel, Z B Özçakar, N Akkök, N Kara, A H Elhan, M , Department of Pediatrics, Osan Korean Hospital, wondong 560-70 , 447-060 Seoul , South Ekim B Acar, F Yalç ›nkaya, S Yüksel, Z B Özçakar, M Ekim: Department of Pediatric Korea Nephrology, Ankara University Faculty of Medicine, Ankara, Turkey N Çakar, N Akkök, N Kara: Department of Pediatric Nephrology, Ministry of Health Ankara Diskapi Education In patients with end stage renal disease, uremic encephalopathy is a common complication and Research Hospital, Ankara, Turkey A H Elhan: Department of Statistics, Ankara expressed by affecting mainly cerebral cortex. Rarely bradykinetic movement with basal University Faculty of Medicine, Ankara, Turkey Presenting author: F Yalç ›nkaya ganglia lesion are reported in uremic patient. Here we described a diabetic patient receiving Ankara University Faculty of Medicine , Department of Pediatric Nephrology, Ankara peritoneal dialysis who developed parkinsonian feature with both basal ganglia lesions in University Faculty of Medicine, Ankara, Turkey , 06510 Ankara , Turkey company with a deterioration of renal function and showed rapidly improving clinical course after enhancement of the dialysis adequacy. The patient is 18-year-old man with The adverse effect of peritonitis and the duration of dialysis on peritoneal membrane chronic renal failure due to focal segmental glomerulosclerosis, diabetes mellitus, function and clinical outcome were evaluated in this study. The study comprised 24 CPD hypertension during 4 years. He started the peritoneal dialysis 4 month ago. In January patients that were followed up in our center at least for 6 months. Their peritoneal functions 2006. Two weeks earlier he had been decreasing residual urine volume and increasing BUN were evaluated at the beginning and during the study period, regularly. The mean age of the and serum creatinine. At admission, neurologic examination demonstrated a parkinsonian patients was 15.3±3.6 years (range 7-20 years). The mean follow period was 50.4±26.8 syndrome, characterized by resting tremor, bradykinesia and postural balance disturbance. months (range 12-114 months). There were 37 episodes of peritonitis during the study cognition was normal. Laborative data showed elevated BUN(66 mg/dL) and creatinen period. The peritonitis rate was calculated as 1 episode / 32.7 patient month. Twenty (10.6 mg/dL), but other blood chemistry were within normal limits. MRI imaging revealed children were on CAPD and 4 on CCPD. RRF showed a negative correlation with the bilateral and symetrical basal ganglia lesions with edema and increased vascularity. thereby duration on dialysis (r=-0,623, p= 0,006).There was no significant correlation between RRF lateral ventricles were compressed. T1-weighted scan showed hypoinense areas in lenticular and nPCR, level of Hb, Hct, albumin and the dose of EPO. A positive correlation was found nuclei, where a T2-weighted images documented hyperintensity in same resions and on with RRF and fluid removal (r=0,482, p=0,043). The total fluid removal was found not to PET imaging the decreased glucose metabolism was noted at both basal ganglia. After be correlated with the presence of hypertension. Higher doses of Kt/Vurea are associated frequency and density of peritoneal dialysis were increased, bradykinetic movement and with higher protein intake (r=0,503, p=0,024). A positive correlation was found between tremer were improved gradually and At four weeks follow up-MRI, previous basal ganglia Kt/Vurea and Hb-Hct levels. The dialysis adequacy tests were found not to be affected by lesions and edema were recovered markedly. the frequency of peritonitis. The most important factor for the prevention of hypervolemia in chronic peritoneal dialysis patients is RRF. Anemia and malnutrition are less improving with the patients who have high Kt/Vurea levels. Therefore preservation of RRF and increase of dialysis adequecy is essensial for children on chronic peritoneal dialysis. 1624 Pediatr Nephrol (2006) 21:1493–1635

COD. PP 409 COD. PP 410 CHANGING PERTONITIS RATE AND AETIOLOGY IN VENOUS COLLAPSIBILITY INDEX CHANGES IN CHILDREN ON CHILDREN ON CHRONIC PERITONEAL DIALYSIS PERITONEAL AND HEMODIALYSIS I Zagozdzon ( presenting author), A Zurowska, I Balasz, I Lesniewska P Hac›omeroðlu1,O Ozkaya2, N Günal1, K Baysal1 1 Ondokuz May›s University, Faculty Medical University of Gdansk , Department Paediatric Nephrology , 80-211 Gdansk , of Medicine, Dept. of Pediatric Cardiology, Samsun-Turkey. 2 Ondokuz May ›s University, Poland Faculty of Medicine, Dept. of Pediatric Nephrology, Samsun-Turkey. Ondokuz may›s University Faculty of Medicine , Department of Pediatric Nephrology , Gram-positive organisms have been the most frequent cause of peritonitis in children 55139 Samsun , Turkey treated with peritoneal dialysis. Lately several reports have underlined the increasing incidence of gram-negative infections. The study presents the changing rate and aetiology AIM:The aim of this study is to investigate the validity of vena cava collapsibility index of peritonitis in children at a single centre over 12 years (1994-2005). (CI) as a parameter to evaluate fluid overload in children on dialysis. Material and methods: The rate and aetiology of peritonitis was assessed in three METHODS: 16 peritoneal dialysis (CAPD) patients, 9 hemodialysis (HD) patients ages consecutive 4-year periods. During a total 1199 patient-months of dialysis 44 episodes of ranged from 5-18 years were enrolled into the study. Twenty-seven age and sex- matched peritonitis were observed. healthy children served as the control group. Results: 1.A significant decrease in peritonitis rate was noted from 1:19 to 1:39 RESULTS: CI was significantly lower in HD patients (19, range: 8.6-38.5) before HD episode/patient-months (TableI). procedure and in CAPD group (25.3 range: 4.1-34.4) before dialysate exchange when 2.The incidence of gram-positive infections decreased (1:25 v. 1: 195) and gram-negative compared with the controls (35.9, range:23.3-46.8) (p=0.021, p=0.001 respectively). No remained constant (1:109 v. 1:65). significant difference was found between CAPD and HD groups. When we compared the 3.A relative increase in gram-negative peritonitis was noted (TableII). change in CI before and after HD, we observed a significant increase in CI (p=0.015). Conclusions: Although, the change in CI values before and after dialysate exchange was significant in 1.The dramatic decline in incidence of peritonitis rate is caused by the decrease of gram- CAPD group (p=0.039), there was still a significant difference (p=0.001) between the CI positive infections. values of the control group and CAPD patients after dialysate Exchange. 2.The lack of simultaneous improvement in the incidence of G(-) infections leads to a CONCLUSION: We suggest CI is a sensitive parameter to assess fluid status in dialysis relative prevalence of G(-) peritonitis in our population. patients. The finding that CI is increased after exchange in CAPD despite the little amount of UF, suggests that CI is also a reliable method in CAPD patients. Measurements of IVC diameters may help to guide physcians for CAPD therapy.

COD. PP 411 COD. PP 412 Comparison of glucose versus icodextrin based peritoneal fluid (PD) Proteomic appliance in peritoneal fluid of children on PD with proteomic techniques in children R Raaijmakers, W Pluk, , C H Schröder, L A H Monnens, J L Willems, L P W J van den R Raaijmakers, W Pluk, C H Schröder, L A H Monnens, J L Willems, L P W J Van den Heuvel Heuvel , UMC St Radboud, dept of pediatric nephrology, Geert grooteplein zuid 10 , 6525 GA , UMC St Radboud, dept of pediatric nephrology, Geert grooteplein zuid 10 , 6525 GA Nijmegen , The Netherlands Nijmegen , The Netherlands Objective: Proteomics offers a high-throughput analysis of the expression of proteins. Objective: Proteomic technologies in PD offer a high-throughput analysis of the proteins in Peritoneal dialysis (PD) is the most frequently used renal replacement therapy in children. peritoneal fluid and can give important information about the functioning of the peritoneal The proteome of PD fluid gives important information about the functioning of the membrane under different circumstances. In this study 3.86% glucose was compared to peritoneal membrane icodextrin. Patients and methods: The dialysate of 3 pediatric PD patients was freshly collected from Methods: The dialysate of 6 matched pediatric PD patients was collected from 2-hour night-time 2-hour dwells with 1,36% glucose. Samples were concentrated and run on a 10% samples of peritoneal equilibrium tests, 3 glucose and 3 icodextrin samples. PD samples SDS-PAGE gel, followed by in-gel digestion with trypsin and separation with nanoscale were concentrated and separated on a 10% SDS-PAGE gel and digested with trypsin. high performance liquid chromatography (nHPLC). Peptides were eluted into the LTQ-FT Peptides were eluted into the LTQ-FT mass spectrometer by nano-electrospray ionization. mass spectometer (MS). Peptide mass and sequence were determined by subsequent MS Peptide mass and amino acid sequence were determined by subsequent MS and MS/MS and MS/MS cycles. cycles. Mass spectometer data files were searched using Mascot. Results: A total of 322 proteins was identified in the PD fluid of the 3 patients. The 3 Results: A total number of 304 proteins was identified in the PD fluid of the 6 patients. patients had 44,6% of all proteins in common. One hundred and three proteins were Proteins of interest concerning functioning and defense mechanisms of the membrane that identified with more than 2 peptides per protein in at least 2 patients. These proteins were were found uniquely in the three icodextrin samples but not in the three glucose samples subdivided into 8 classes based on molecular function. Most abundantly found were were neutrophil defensin-1 and angiogenin. Fibulin-1was found only in all three glucose albumin, alpha-2-microglobulin, apolipoproteins, complement factors, fibronectin en samples but in none of the icodextrin samples. serotransferrin. Remarkable proteins with possible immunological and infectiological Conclusion: The proteome of different PD fluids gives insight in the different processes that impact were lipocalin, gelsolin, histidin-rich glycoprotein amongst others. Another occur in these fluids. Some interesting proteins were found only in all glucose PD samples important substance was angiotensinogen. and in none of the icodextrin PD samples and vice versa. In these group interesting proteins Conclusion: This study gives the first oversight of the proteome of PD fluid. The proteome occurred, indicating a possible different pattern of inflammation and angiogenesis in reflects plasma proteins and local peritoneal processes. Potentially interesting proteins are icodextrin- versus glucose based PD fluids. Further reseach is needed to elucidate the exact revealed. More research will be needed to elucidate the function and meaning of these meaning of these findings. proteins for PD, and to identify biomarkers for complications of PD Pediatr Nephrol (2006) 21:1493–1635 1625

COD. PP 413 Intraperitoneal darbepoietin in the treatment of anemia in children on peritoneal dialysis (PD) Y Rijk, R Raaijmakers, N C A J Van de Kar, C H Sch röder , UMC St Radboud, dept of pediatric nephrology, Geert grooteplein zuid 10 , 6525 GA Nijmegen , The Netherlands

Objective: to determine the efficacy and safety of intraperitoneal administration of darbepoietin in children with renal anemia on nightly intermittent peritoneal dialysis. Patients and methods: 21 children were included (mean age was 6.9 years; range 0-17). Nine of them (subgroup A) were converted from erythropoietin thrice weekly to darbepoietin once weekly, using a conversion factor of 200 U erythropoietin = 1 ìg darbepoietin. Twelve children (subgroup B) started darbepoietin once weekly with an initial dose of 0.45 ìg/kg/week. Darbepoietin was administered during the daytime in 50 mL of dialysis solution. Results: subgroup A was treated for a median period of 31.5 months. Median darbepoietin dose over this period was 0.79 ìg/kg/week; median haemoglobin concentration 7.3 mmol/l (11.8 g/dl). Subgroup B was treated for a median period of 13.0 months (median darbepoietin dose 0.59 ìg/kg/week; median haemoglobin 7.0 mmol/l (11,3 g/dl)). The total group (N=21) was treated with darbepoietin for a median period of 13.4 months The median darbepoietin dose was 0.63 ìg/k/week, and the median haemoglobin concentration 7.1 mmol/l (11.5 g/dl). The peritonitis incidence during the study was 1 episode every 25.1 months. Three children developed hypertension, and 1 headache, after a rapid rise in haemoglobin concentration; all complaints spontaneously recovered. Conclusion: intraperitoneal administration of darbepoietin is effective and safe for the treatment of renal anemia in children on peritoneal dialysis. Dosage needed is not extremely high, and the incidence of infectious complications is not increased. 1626 Pediatr Nephrol (2006) 21:1493–1635

AUTHORS INDEX OP 29, OP 45, OP 48, Bakr A. PP 325, PP 326, Bek K. PP 57, PP 111, PP 218 PP 339, PP 377 PP 261, PP 333, PP 399 Abeyagunawardena A.S. Amr M. PP 325, PP 326, Balasz I. PP 330, PP 409 Belk R. PP 168, PP 173 OC 5, PP 54 PP 339 Baáasz-Chmielewska I. Bellanné-Chantelot C. Abramishvili N. PP 374 Anarat A. PP 7, PP 196, PP 397 OP 1, OP 38 Acar B. OC 19, PP 407 PP 360 Bald E. OP 46 Bellantuono R. PP 193, Aceto G. PP 61, PP 63 Anders D. PP 74 Bald M. PP 356 PP 312 Adamczyk P. PP 314 Andersone I. PP 87 Balegno S. OP 45, OP 48 Ben-Abdallah R. PP 238 Afanetti M. PP 10, PP 322 Andre J. PP 222 Balice P. OP 19, PP 13 Benetti E. PP 154, PP 186, Afgan A. PP 136 André J.L. OP 12, OP 17 Balletta M.M. PP 382 PP 188 Afifi H.M. PP 114 André J.M. PP 131 Balluch B. PP 171 Bensman A. OP 17, Afonso C. PP 42, PP 256 Andreasson A.C. OP 20 Baltesova T. PP 91, OP 29, PP 103, PP 201, Agachan B. PP 250 Andreeva E.F. PP 161 PP 291, PP 292 PP 251, PP 352, PP 353, Agapov E. PP 345 Anglani F. PP 16, PP 235 Balzamo E. PP 205, PP 363 Agras P.I. PP 293, PP 341 Anthopoulou A. PP 79 PP 354, PP 355 Benz M.R. PP 125 Aguirre M. PP 209 Antignac C. OP 39, PP 189 Bandin F. OP 1, OP 38 Berard E. PP 10, PP 322 Ahlenstiel T. PP 224 Antikainen M. PP 38 Bangen U. PP 340 Berdeli A. PP 32, PP 51, PP 225, PP 227 Antoniewicz J. PP 316, Banki N.F. PP 212 PP 279 Ahmadzadeh A. PP 350 PP 327 Bänziger O. PP 403 Berding G. PP 226 Ahmed S.F. PP 309, Antoniewicz T. OC 10 Bao A. PP 172 Bereczki C. PP 285 PP 310 Antonijevic-Jeftenic N. Barath A. PP 285 Bereczki C.S. PP 146, Ahn H.S. PP 182 PP 121 Barbano G. OP 36 PP 379 Akalın F. OP 59 Ardissimo G. PP 49 Barisoni L. PP 195 Berg U.B. PP 208 Akbas H. OP 8, OP 50, Ariceta G. PP 172, PP 209 Barrios E. PP 268, PP 270, Berger C. OP 18 PP 271, PP 272 Arjemandi K.H. PP 22, PP 302 Bertini E. PP 195 Aki F.T. PP 243 PP 24 Barzon L. PP 234 Bertola L. OP 48, PP 218 Akil I. PP 50, PP 282 Armas Suarez A. PP 268 Basaran C. OP 15 Besbas N. OP 15, PP 53, Akkaya B. OP 8 Armin S. PP 276 Basarla H. PP 300 PP 100, PP 243, PP 284, Akkoc T. PP 55 Armstrong V.W. OP 23 Bascands J.L. OP 30 PP 295, PP 347, PP 389 Akkök N. PP 282, PP 407 Artan R. PP 183 Basiratnia M. PP 396 Besouw M.T.P. PP 166 Akman S. OP 8, OP 50, Artifoni L. PP 16, PP 154, Baskin E. PP 53, PP 196, Bettinelli A. OC 7, OP 59, PP 158, PP 183, PP 186, PP 235 PP 245, PP 261, PP 282, PP 124, PP 160, PP 169, PP 271, PP 272, PP 282 Asano Y. PP 43, PP 99, PP 293, PP 341 PP 278 Aksu N. OP 59 PP 381 Basta-Jovanovic G. Bianchetti M.G. OC 7, Al Bokhrhli J. PP 79 Askiti V. PP 289, PP 395 PP 136 PP 127, PP 160, PP 278, Al Hashemi G.H. PP 396 Aslan S. PP 282 Bates D.O. OP 3 PP 280 Al Mosawi A.J. PP 170, Ataii N. PP 396 Batiniü D. PP 346 Bideci A. PP 296 PP 194, PP 315, PP 318 Atalay E. PP 399 Batrakova I. PP 62 Biebuyck N. PP 223, Aladag S. PP 401 Attanasio M. PP 164 Baudet-Bonneville V. PP 355 Ala-Houhala M. PP 38 Attila G. PP 7, PP 360 PP 353 Biernacka A. PP 163 Al-Aiouty M. PP 329 Awan A. PP 228, PP 232 Baudouin V. OP 17, Bigbee W. OP 21 Alberti C. OC 8, PP 175 Ayata M. PP 385 OP 32, PP 249, PP 383 Bikmaz Y.E. PP 196 Al-Haggar M. PP 329 Aydin B. PP 263 Baverel G. PP18, PP 19 Bilge I. PP 250 Alimo÷lu E. PP 158 Aydın F. PP 158 Bayazıt A. PP 261 Bilginer Y. OP 15, Alkhatib S. PP 41 Aytekin A. PP 143 Bayazit A.K. PP 7, PP 100, PP 284, PP 295, Alkushi A. PP 393 Azéma C. PP 242 PP 282, PP 360 PP 391 Allain-Launay E. OC 11, Aziza J. OP 1 Bayreuther J. OP 24 Bircan Z. PP 76, PP 141, PP 222 Azor D. PP 118 Baysal K. PP 111, PP 261, PP 282, PP 294, Almeida M. PP 239 Bael A. PP 71 PP 333, PP 410 PP 388 Alonso A. OP 27, PP 17, Baiko S.V. PP 104, PP 305 Baysal Y.E. OP 8, OP 50, Bisesti V. PP 382 PP 185, PP 187 Bakkaloglu A. OP 15, PP 183, PP 271- PP 272 Bismuto R. PP 273 Alpay H. OP 9, OP 59, OP 59, PP 53, PP 100, Bazina M. PP 365 Bitner-Glindzicz M. PP 8, PP 55, PP 58, PP 275 PP 102, PP 243, PP 282, Beck B.B PP 179, PP 229, PP 168, PP 173 Alshaya H.O. PP 393 PP 284, PP 295, PP 347, PP 340 Biyikli N. OP 9, PP 6, Altas B. PP 253 PP 389, PP 391 Beck J. OP 34 PP 8, PP 9, PP 55, PP 58, Álvarez Ramos R. PP 26 Bakkaloglu M. PP 243 Beck M. PP 174 PP 275 Alvarez-Garcia O. PP 317, Bakkaloglu S. PP 72, Becker T. PP 225 Blahova K. PP 159 PP 319, PP 320 PP 282, PP 297 Bedir A. PP 333 Blanchard A. PP 176 Ambrosetti D. PP 322 Bakkaloglu S.A. OP 59, Bednorz R. PP 94, PP 335 Blanchard G. PP 131 Amessou M. PP 254 PP 143 Behets G.J. PP 301 Blanche S. PP 138 Amore A. OC 13, OP 16, Bakki J. PP 146 Behne D. PP 311 Blom H. PP 177 Pediatr Nephrol (2006) 21:1493–1635 1627

Blom H.J. PP 166 Buyan N. PP 72, PP 143, Cha S.H. PP 402 Corrado C. PP 144, BlumczyĔski A. PP 97 PP 297, PP 333 Chae Y.S. PP 82 PP 145, PP 299 Bode-Böger S.M. PP 106 Buyukcelik M. PP 7, Chami L. PP 10, PP 322 Cortina G. PP 368 Boćová I. PP 64 PP 360 Champion G. PP 180 Costantini D. OP 51 Bogdanovic R. PP 115, Cabral A. PP 239 Charalambous S. PP 73 Coward R.J. OP 3, PP 15 PP 136, PP 298 Cachat F. OP 19, PP 13, Charbit M. OP 28, PP 223 Coward R.J.M. OC 4 Boguszewska A. PP 330 PP 134, PP 281, PP 311 Charpentier A. PP 251 Cransberg K. PP 20 Boguszewska-Bączkowska A. Caglar F. PP 263 Charrie A. PP 131 Csiky B. PP 106 PP 397 Caglayan C. PP 76 Chen Y.W. PP 12 Curley J.F. PP 11 Boillot O. PP 215 Cakalagaoglu F. OP 9, Cheong H.I. PP 165, Cusi D. PP 213 Bökenkamp A. PP 119, PP 8 PP 182 Cvitkoviü-Kuzmiü A. PP 171 Çakar N. PP 253, PP 259, Chiesa M. OP 45 PP 346 Bölter D. PP 74 PP 261, PP 282, PP 407 Chimenz R. PP 59, PP 84, Czarniak P. PP 152, Bonet B. PP 89 Calabrese R. PP 61, PP 304 PP 262 Bongers E.M.H.F. OP 40 PP 63, PP 193 Chitano G. OP 51 Czupryniak A. OP 41, Bonofiglio R. PP 266 Calderan A. PP 101 Cho B.S. PP 1, PP 343 OP 46 Bonzel K.E. OP 39 Calevo M.G. PP 404 Cho H.Y. PP 165 D`Angelo F. OP 47 Bordugo A. OC 2 Caliskan S. OP 59, PP 261 Cho K.H. PP 34 D`Arcangelo R. OP 47 Borojeviü I. PP 346 Calò L. PP 169 Cho Y.M. PP 133 D`Armiento M. OP 47 Borsa N. OC 7, PP 160, Camilla R. OC 13, OP 48 Chodór B. PP 260 D’Alessandro M.M. PP 169, PP 278 Campanaro S. PP 16 Choi Y. PP 165 PP 144, PP 145, PP 299 Borzych D. OP 56 Can B. PP 57 Choroszy-Krol I. PP 94 D’Anna F. PP 145 Bosáková A. PP 75 Canan O. PP 341 Chretien A. PP 237 D’Haese P.C. PP 301 Bottazzo G.F. PP 200 Canda E. PP 50 Christians U. PP 241 D’Urbano L. PP 5 Bouba I. OP 2 Candiano G. OP 57 Chumakova O. PP 303 Da÷demir A. PP 111 Boubaker A. OP 19, PP 13 Canpinar H. PP 389 Chwatko G. OP 46 Dagnino M. PP 188 Boudailliez B. PP 180 Canpolat N. PP 282 Chybicka A. OP 10 Dalirani R. PP 30, PP 85 Bouissou F. OP 17, OP 29, Cansick J.C. PP 306 Chyczewski L. OP 42 Dallocchio A. PP 375, OP 30, OP 38, PP 242 Canterino I. PP 45 Cigerdelen N. PP 401 PP 378 Bourdat G. OP 29 Capasso G.B. OP 48, Cinaz P. PP 297 Daneshmand H. PP 276 Bourillon A. OC 8, PP 175 PP 277 Cingi E. PP 296 Daniel V. PP 210 Bouts A.H. PP 214 Capizzi A. PP 16, PP 154 Ciofi M. PP 117 D'Armiento M. PP 382 Bouvier R. OC 8, PP 175, Capra M. PP 145 Clara A. PP 368 Darreye G. PP 367 PP 191, PP 367 Caprioli A. PP 117 Claverie-Martín F. Davin J.C.M.A. PP 214 Boyer O. PP 190, PP 205, Carasi C. OP 44, PP 154, PP 162, PP 268 Davin J.C. PP 40 PP 355 PP 234, PP 235 Cloarec S. PP 222 De Benedetti F. PP 5 Bozkurt N. PP 58 Carbajo E. PP 317, Coache C. PP 322 De Blasio G. PP 213 Braida F. PP 98 PP 320 Cochat P. OP 12, OP 16, De Broe M.E. PP 301 Bravo J. OP 27, PP 185 Carbajo-Perez E. PP 319 OP 25, OP 29, PP 18, De Capua B. OP 51 Brigotti M. PP 117 Cardillo M. PP 235 PP 19, PP 45, PP 131 De Felice C. OP 51 Brito I. PP 256 Carev D. PP 14 PP 180, PP189, PP191, de Graaf-Hess A. PP 177 Brncic N. PP 373 Caridi G. PP 5, PP 188, PP 215, PP 368 De Palo T. PP 117, PP 193, Brochard K. PP 190 PP 195 Codina G. PP 199 PP 312 Brogan P.A. PP 230 Caringella D.A. PP 193, Codoceo R. PP 17 De Pieri M. OP 36, PP 234 Brossard V. PP 56 PP 312 Cohen S. OP 28, PP 205 De Rosa A. PP 382 Broux F. OP 17, PP 56 Caropreso M. OP 47, Colak O. PP 263 De S. PP 372 Brummer C. OP 60 PP 382 Collard L. OP 29 De Terlizzi F. OC 13 Brundler M.A. PP 255 Caropreso S. OP 36 Collardeau S. PP 367 de Wijs I. J. OP 40 Bruschi M. OP 57 Carsetti R. PP 200 Collin S. OP 35 Deanfield J. OC 14 Bruyn R.D. PP 204 Casagrande F. PP 10 Colluto L. PP 16 Debiec H. PP 353, PP 367 Brzewski M. PP 342 Castagnetti M. PP 398 Colonna F. PP 98 Dechaux M. PP 138 Buechner K. OP 18 Cava F. PP 89 Coltella V. PP 312 Decramer S. OP 1, OP 30, Bulla M. OP 25, PP 122, Cean M. PP 118 Colussi G. OC 7 OP 38, PP 242 PP 202 Celci G. OC 9 Conlon P. PP 228 Dede B. PP 399 Bunker-Wiersma H.E. Celik U.S. PP 360 Conti G. OP 48, PP 59, DČdek P. PP 29 PP 214 Cengiz N. PP 196, PP 245, PP 84, PP 218, PP 304 Dedeoglu N. OP 50, But I. OP 11 PP 293, PP 341, PP 360 Coppa G.V. PP 69 PP 271, PP 272 Buturoviü J. PP 108, Cengiz Ozyurt B. PP 50 Coppo R. OP 16, OP 45, Dehennault M. PP 238 PP 308 Centi S. PP 16, PP 154, OP 48, PP 218 Del Gado R. OC 1, PP 96, Buturovic Ponikvar J. PP 235 Cordier M.P. PP 191 PP 273 PP 113 Cetinel S. PP 6, PP 9 ûoriü M. PP 346 Del Gaizo D. OC 1 1628 Pediatr Nephrol (2006) 21:1493–1635

Del Prete D. PP 154 Dubrel M. PP 363 Falger J. PP 217 OP 12, PP 249, PP 251, Delezoide A.L. OC 8, Durak H. PP 156 Falger J.F. PP 403 PP 354 , PP 355, PP 383 PP 175 Duret R. PP 118 Fallahzadeh M.H. PP 396 Frezzolini A. OP 36 Delfino L. PP 213 Dursun H. PP 7, PP 360 Fargue S. OP 12, PP 180, Froede K PP 227 Della Vella M. PP 16, Dursun ø. PP 150, PP 178, PP 191, PP 368 Frolov B. PP 362 PP 154, PP 234, PP 235 PP 267 Farron F. PP 134 Fründ S. PP 122, PP 171 Dello Strologo L. PP 200 Dušek J. OP 26, PP 39, Fdez-Iglesias J.L. PP 172 Füzesi K. PP 146 Ĉelmiš J. PP 346 PP 257, PP 287, PP 364 Feather S. OC 14 Gagnadoux M.F. OP 28, Delobbe J.F. PP 131 Dust N. OC 6 Feather S.A. PP 168, OP 29, PP 180, PP 205, Delous M. PP 189 Düúünsel R. PP 150, PP 173 PP 223, PP 354, PP 355 Del Rio M. PP 246 PP 178, PP 267 Feber F. PP 337 Gaido M. OC 13, PP 117 Demir K. PP 77 Duzova A. OP 15, PP 100, Feber J. OC 6, PP 237, Gajjar P. PP 52 Demirci D. PP 150, PP 267 PP 243, PP 261, PP 282, PP 338 Galeeva N. OP 43 Demirkaya E. PP 139, PP 284, PP 295, PP 347, Fede C. PP 59, PP 84, Gallizzi R. PP 59, PP 84, PP 140 PP 391 PP 304 PP 304 Denamur E. OC 8, PP 175 Dvorak P. OP 26, PP 39, Fedorov D. PP 357 Gallo M. PP 382 Derakhshan A. PP 350, PP 257, PP 287 Fehrenbach H. OP 25 García E. PP 317, PP 319, PP 396 Dziedzic A. PP 328 Fekete A. PP 212 PP 320, PP 321 Derbent M. PP 196 Edefonti A. PP 49, PP 117, Fella A. PP 48, PP 128, García Meseguer C. OP 27 Deschênes G. PP 10, PP 206, PP 213, PP 216, PP 334, PP 336 García-Nieto V. PP 162, PP 103, PP 201, PP 251, PP 323, PP 332, PP 404 Fencl F. OP 26 PP 172, PP 268, PP 269, PP 352, PP 353, PP 363 Efremidis S.C. PP 79 Feneberg R. OC 19, PP 270, PP 302 Devange J. PP 179, Egemen A. PP 50 PP 211, PP 220, PP 221 Garnier A. OP 32 PP 229, PP 340 Eggermont J. OP 3 Fernández C. PP 17, Geary D. PP 105 de Ville de Goyet J. OP 29 Ehrich J.H. PP 224 PP 185, PP 187 Gedik N. PP 6, PP 9 Dheu C. OC 20, PP 202, Ehrich J.H.H. PP 225, Fernandez Camblor C. Geelen G. PP 131 PP 223 PP 226, PP 227, PP 258 OP 27 Geelen J. PP 254 Di Giandomenico S. Eickelberg O. PP 148 Fernandez M. PP 321 Geier P. PP 157, PP 364, PP 195 Ekim M. OP 59, PP 253, Fernando O.N. PP 207 PP 384 Di Tommaso E. PP 304 PP 259, PP 261, PP 282, Ferraresso M. PP 206 Geisler S. PP 226 Diana A. PP 281 PP 407 Ferretti A.V.S. OP 47, Gellermann J. PP 181, Diercke M. OC 12 El-Din F.S. PP 123 PP 117 PP 258 Dillon M.J. OP 33 Elhan A.H. PP 407 Feuerstein D. PP 246 Génin E. OP 39 Dinler A. OP 13 El-Khawaga A. PP 313 Feuillard J. PP 375, Genzel-Boroviczeny O. Diomedi-Camassei F. Ellins E.A. OC 14 PP 378 PP 125 PP 195 El-Mogy A. PP 325, Fidan K. PP 297 Georgiou I. OP 2 Dissaneewate P. PP 120 PP 326, PP 339, PP 377 Filiz S. OP 50, PP 271, Gerard B. OC 8, PP 175 Distilo A. PP 84 El-Refaey A. PP 325, PP 272 Gharib A. PP 276 Djordjevic G. PP 373 PP 326, PP 339, PP 377 Filler G. OC 6, PP 237, Ghiggeri G. PP 5 Djordjevic M. PP 298 El-Sayed S.S. PP 114 PP 241, PP 337, PP 338 Ghiggeri G.M. OP 57, Dlin V. OP 43, PP 345, Emma F. OP 14, OP 36, Fiorenza M. PP 367 PP 188, PP 195, PP 235 PP 357 PP 5, PP 117, PP 160, Fisch T. OP 7 Ghio L. PP 49, PP 206, Dodat H. PP 45 PP 195, PP 200, PP 404 Fischbach M. OC 20 PP 213, PP 216, PP 235 Dolezel Z. PP 384 Emmanouilidou A. OP 2 Fischer W. OP 25 Ghirardo G. PP 235 Donald A.E. OC 14 Emond S. PP 205 Fitöz S. PP 253, PP 259 Giacomini A. OC 2 Donmez O. PP 401 Emre S. PP 250 Fitzpatrick M.M. OP 33 Giani M. OP 48 Ĉorÿeviü G. PP 346 Erdem S. OP 59 Flajšman S. PP 346 Gianoglio B. OC 13, Dragon-Durey M.A. Erdogan S. PP 7 Flajsman-Raspor S. PP 404 OP 12, PP 249, PP 354, Erdur B. PP 156 PP 90, PP 373 Gianviti A. OP 36, OP 48, PP 383 Ergen A. PP 250 Flogelova H. PP 157 PP 117 DroĪdĪ D. OP 39, PP 107, Ergün, H. PP 253 Flück C. PP 281 Gil H. PP 317, PP 319, PP 109, PP 260, PP 328, Eser E. PP 50 Foster R.R. OP 3 PP 320 PP 330 Esfehani S.T. PP 396 Fotopoulos A. PP 79, Gil M. PP 172 DroĪdĪ M. PP 328 Esmael A. PP 300 PP 359 Gilbert R.D. OP 33, PP 21 Drozynska-Duklas M. Espino M. PP 89 Foulard M. OP 25, PP 189, Gill D. PP 228, PP 232 PP 152, PP 262 Espinosa L. OP 27, PP 185, PP 238 Gillion O. OP 28, PP 223 Drube J. PP 122 PP 187 Francioso G. PP 63 Ginevri F. PP 235 Drueckler E. OP 55, Eurin D. PP 56 Franco C. PP 63 Giordano M. PP 193, PP 231 Evim M. PP 394 Freeman K. PP 246 PP 312 Dubourg L. PP 18, PP 19, Exantus J. PP 118 Freemont A. PP 307 Girardin E. OP 18, OP 19, PP 45, PP 215 Faheem M.S. PP 114 Frémeaux-Bacchi V. OP 29, PP 13 Pediatr Nephrol (2006) 21:1493–1635 1629

Glavina-Dundov M. OP 50, PP 183, PP 271, Hickey D. PP 228 PP 381 PP 346, PP 365 PP 272 Hiedl S. PP 125 Jachimiak B. PP 35 Glöckner J. PP 125 Gurgey A. PP 102 Hildebrandt F. PP 164 Jacquemont S. PP 134 Gobber D. PP 101 Gürgöze M.K. PP 150, Hinard C. PP 134 Jagger J.E. PP 241 Gockowska Z. PP 262 PP 178, PP 267 Hiorns M. OC 14 Jahnukainen T. OP 21, Goeggel B. PP 281 Güven A.G. PP 158 Hirche H. PP 71 PP 38 Gok F. PP 139, PP 140 Guyot C. OC 11, PP 189, Hladik M. PP 364 Jain M. PP 344 Gökçe ø. PP 55, PP 58, PP 222 Hladikova M. PP 39 Jalanko H. OC 3, PP 219 PP 275 Györke Z.S. OC 15 Höcker B. OC 12, PP 210, Janas R. OP 52 GoáĊbiewski A. PP 152 Ha I.S. PP 165 PP 211 Jancova E. PP 364 Golikhani F. PP 396 Ha T.S. PP 68 Hoecker B. OP 23, OP 25 Janda J. OP 26, PP 39, Golitsina E. PP 357 Habbig S. PP 229 Hoeflich A. OP 7 PP 159, PP 257, PP 287, Gombos É. OC 15 Haberal M. PP 245, Hoefsloot L.H. OP 40 PP 364 Gonen S. PP 143 PP 293 Hoemme M. OP 7 Jander A. PP 330, PP 397 Gonlusen G. PP 7, PP 196 Haciomero÷lu P. PP 410 Höfele J. PP 125 Jandeska S. PP 11 González-García M. Hackert T. OP 58 Hofer K. PP 368 Janner M. PP 281 PP 269 Hackiewicz L. PP 126 Holder M. PP 356 Janssen F. OP 29, PP 180 González-Paredes F.J. Hadj-Aïssa A. PP 18, Holmberg C. OC 3, PP 219 Jardim H. PP 42, PP 80, PP 162 PP 19 Holscher H.C. PP 31 PP 256 Granados A. PP 89 Hadjiyannakis S. OC 6 Holt R.C.L. PP 324 JarmoliĔski T. PP 35, Grassi M.R. PP 49 Haffner D. OC 12, OP 55, Hömme M. OP 58, PP 148, PP 112, PP 184, PP 330 Grassia C. PP 93 PP 231, PP 301 PP 149 Jasonni V. PP 398 Graziano L. PP 93, Hak J. PP 29 Hong H.J. PP 34 Javouhey E. PP 131 PP 273, PP 274 Hakimzadeh M. PP 350 Hong S.J. PP 376 Jayachandran A. PP 148 Grbac T. PP 90 Hamed A.H. PP 114 Hooman N. PP 22, PP 24, Jeck N. PP 125, PP 139, Greco R. PP 266 Hammad A. PP 325, PP 27, PP 396 PP 140, PP 141 Greenstein S. PP 246 PP 326, PP 339, PP 377 Hoppe B. OP 25, PP 179, Jenkins D. PP 168, PP 173 Gregorini G. OP 45 Hanci S. PP 394 PP 210, PP 229, PP 265, Jeong H.J. PP 252, PP 358 Grenda R. OP 52, PP 316, Hansson S. OP 20 PP 340 Jeong I.C. PP 402 PP 327, PP 397 Haq M.R. OP 33 Horáková J. PP 64 Jeunemaître X. PP 176, Gribouval O. PP 189 Harambat J. PP 45, Horen B. PP 242 PP 190 Griebel M. PP 122 PP 215 Horuk R. PP 148 Jhang W.K. PP 288 Grimaldi M. PP 96 Harputluoglu F. PP 141 Hothi D.K. PP 105 Jin D.K. PP 400 Grkoviü L. PP 346 Harvey B. PP 116 Houillier P. PP 176 Jodal U. OP 20 Groenen P. PP 167 Harvey E. PP 105 Hoyer P. OP 25 Johannes L. PP 254 Groothoff J.W. PP 214 Hasanoglu E. PP 143 Hoyer P.F. OC 18, PP 4 Johansson S. OC 9 Gross J. PP 340 Haszon I. OC 15, PP 379 Hubáþek J.A. PP 212 John U. PP 202 Gruppen M.P. PP 40 Hauskrech M. OP 21 Hubchak S.C. PP 11 Johnson S.A. PP 255, Gubler M.C. OC 8, Hayashida T. PP 11 Huisson A. PP 255 PP 372 PP 175, PP 367 Haycock G.B. PP 135 Hulse E. PP 21 Jones C. OP 33, PP 286 Guc D. PP 389 Hayes J. PP 244 Hulton S.A. PP 255 Jones C.A. PP 324 Gucer S. PP 391 Hébert M.J. PP 12 Hutchinson C. PP 207 Jouvenet M. PP 45 Guest G. OP 28, PP 222, Heckert K.H. OP 60 Huynh Ngoc L. PP 322 Judd B.A. PP 324 PP 223 Hecketsweiller B. PP 56 Hwang Y.S. PP 358, Julita M. OP 4 Guignard J.P. OP 4 Heemann U. PP 212 PP 402 Jungraithmayr T.C. Guigonis V. OP 17, Heidland A. OP 53 Iaccarino F. PP 274 PP 210 PP 352, PP 367, PP 375, Heinen S. PP 122 Ibáñez-Alonso A. PP 269 Jungraithmayr T. PP 368 PP 378 Helou J. PP 164 Iervolino L. R. OC 1 Kabaalio÷lu A. PP 158 Guillou C. OP 1 Hennermann J.B. PP 181 Iglesias C. PP 26 Kabasakal C. PP 32, Gulati S. PP 344 Henriquez-Palop F. Ignatova M. OP 43, PP 387 Gulbas Z. PP 385 PP 269 PP 345, PP 357 Kaddeh A.M. PP 313 Gültekin M. OP 8, OP 50, Hernández González J. Ignatova M.S. PP 66 Kaizer L. PP 380 PP 271, PP 272 PP 302 Ilki A. OP 9, PP 8 Kalay S. OP 8 Günal N. PP 410 Hernández González M.J. Indaco R. PP 336, PP 382 Kalkum G. PP 174 Gündüz Z. PP 150, PP 268, PP 270 Ingelfinger J.R. PP 12 Kalyoncu M. PP 347 PP 178, PP 267 Herrero-Morín J.D. Inward C. OP 33 Kaminska A. PP 88 Güngör F. PP 158 PP 130 Ioannides E. PP 73 Kara N. PP 253, PP 259, Güntekin E. PP 158 Herthelius M. PP 208 Isacchi G. PP 200 PP 407 Gupta A. PP 344 Herweg M. OP 60 Isapof A. PP 201 Kara O.D. OP 59 Gupta G. OP 21 Hesse A. PP 265 Ispir T. PP 58, PP 250 Karagöz F. PP 57 Gür Güven A. OP 8, Heuft H.G. PP 227 Ito N. PP 43, PP 99, Karagüzel G. PP 158 1630 Pediatr Nephrol (2006) 21:1493–1635

Karakayali H. PP 245 Kollataj B. PP 330, PP 397 La Rocca F. PP 145 Leichter H.E. PP 356 Kardelen F. OP 59 Kolska M. PP 364 La Torre F. PP 304 Leitão A. PP 256 Kardos M. PP 351 Kolsky A. PP 364 Lachaux A. PP 215 Lennon R. OP 3, PP 15 Karg E. PP 380 Komarova O. OP 49 Lagercrantz H. OC 9 Lens X.M. PP 172 Kari J.A. PP 393 Komasara L. PP 152 Lahdenkari A.T. OC 3 Leone F. PP 144, PP 145, Karikoski R. OC 3 König K. OC 12 Lahoche A. PP 238 PP 299 Karimi A. PP 85 Konrad M. PP 127, Lama G. OP 48, PP 93, Lepaeva T. PP 345 Karpov A. PP 362 PP 280 PP 273, PP 274 Lesieur L. PP 254 Kartamysheva N. PP 303 Kool M. PP 119 Lama R. PP 17 LeĞniewska B. PP 397 Kasap B. PP 2, PP 3, Koopmans R.P. PP 214 Lamioni A. PP 200 Lesniewska I. PP 409 PP 33, PP 77, PP 156 Kopylov Y. PP 362 Lampe D. PP 237 LeszczyĔska B. PP 397 Kaskel F. PP 246 Kordon Z. PP 328 Landolfo A. PP 200 Letavernier B. PP 201 Kaskel F.J. OP 5, PP 348 Kosiak W. PP 152 Landthaler G. PP 56 Levicheva O.V. PP 41 Katsaraki A. PP 359 Koskimies O. PP 38 Lane P. J. L. PP 372 Levtchenko E. OP 40, Katsarou E. PP 289 Kostic M. PP 236, PP 290 Langer R. M. OP 22 PP 166, PP 177 Katsios O. PP 79 Kostro I. PP 88 Langer T. OP 34 Lewandowska-Stachowiak M. Katysheva O. PP 345 Košuljandiü-VukiüĈ. Lange-Sperandio B. PP 331 Katysheva O.V. PP 66 PP 346 PP 148, PP 149 Licanski A. PP 115, Kaukinen A. OC 3 Kovács L. PP 64 Lapeña S. PP 26 PP 298 Kausman J.Y. PP 203 Kovarik J.M. PP 210 Lapeyraque A.L. OP 17 Licht C. PP 229, PP 340 Kavukcu S. PP 2, PP 3, Koyun M. OP 8, OP 50, Lara E. PP 197, PP 198, Liet J.M. OC 11 PP 33, PP 77, PP 156 PP 183, PP 271, PP 272 PP 199 Lilien M. PP 167 Keleman S. PP 47 Kozareva A.A. PP 161 Larionova V.I. PP 161 Lim A. PP 120 Kemper M. OC 19 Koziell A. OC 4 Laszki-Szcząchor K. Lim I.S. PP 83 Kemper M.J. PP 25, Kozyro I. PP 370 PP 335 Linné T. OP 16 PP 202, PP 217, PP 403 Kral A. PP 107, PP 109 Latif E. PP 396 Linsheng X. OP 6 Keogan M. PP 232 Kranz B. OC 18, PP 4 Latini G. OP 51 Little D. PP 228 Kerkuck L. OP 24, OP 33 Kreisinger J. OP 26, LatoszyĔska J. PP 397 Litwin M. OC 10, OP, 39, Kessler S. OP 1 PP 39, PP 257, PP 287 Latta K. OP 25 OP 52, PP 316, PP 327 KiliĞ-PstrusiĔska K. Kremers A. OP 34 Laube G.F. PP 217, Liu F. PP 12 PP 46 Krid S. PP 205 PP 403 Liutkus A. OP 12, PP 45, Kim D.S. PP 248 Krier M.J. OP 12 Laubova J. PP 147 PP 191, PP 215 Kim H.J. PP 81 Krniü D. PP 14 Lavocat M. P. PP 191 Ljuboja O. PP 47 Kim J.H. PP 82, PP 252 Król–JawieĔ W. PP 107, Lavoratti G. OP 48, Llanas B. PP 180 Kim J.S. OP 54, PP 182 PP 109 PP 404 Lobenhoffer J.M. PP 106 Kim K.H. PP 376 Krstic Z. PP 236 Lax H. PP 71 Loi S. PP 49 Kim M.J. PP 36, PP 37, Kruscic D. PP 236, PP 290 Le Nagard H. OC 8, Loirat C. OC 8, OP 17, PP 248 Krynicki T. PP 97 PP 175 OP 32, PP 175, PP 249, Kim N. PP 182 Krzemien G. PP 88, PP 92 Le Potier N. PP 176 PP 383 Kim P.K. PP 252, PP 390 KsiąĪek E. OP 41, OP 46 Le Pottier N. PP 190 Loredo V. PP 317, PP 320 Kim S. PP 60, PP 182 Kucherenko A. PP 303 Ledesma I. PP 26 Lorton F. PP 103, PP 201 Kim S.D. PP 1, PP 343 Küçükaydın M. PP 150, Lee C.G. PP 165 Losonczy G. OP 22 Kim W.Y. PP 83 PP 267 Lee D.Y. PP 248 Lospalluti L. PP 61 Kim Y.H. PP 288 Kudlickova A. PP 384 Lee E.J. PP 68 LĘwik M. PP 167 King D. PP 309, PP 310 Kukla E. PP 146 Lee H.S. PP 83 Luchaninova V.N. PP 264 Kiray M. PP 2 Kukul E. PP 158 Lee H.Y. PP 400 Ludwig K. PP 25 Kirschfink M. PP 122 Kumar A. PP 344 Lee J.H. PP 133, PP 288, Ludwig M. PP 171 Kirschstein M. OP 16 Kural N. PP 263, PP 385, PP 371 Lühr A. PP 226 Kisohara S. PP 43, PP 99 PP 394 Lee J.S. OP 37, PP 36, Luis Yanes I. PP 302 Kist-van Holthe J.E. Kural Y. PP 394 PP 37, PP 248, PP 252, Luis Yanes M.I. PP 269, PP 31 Kuralay F. PP 2, PP 3 PP 358, PP 402, PP 408 PP 270 Klaus G. OP 25, PP 406 Kurcinova Z. PP 91 Lee J.W. PP 81 Luk D. OP 33 Klein T. PP 29 Kutílek Š. PP 28, PP 151 Lee M.K. PP 133, PP 288, Lukáþ J. PP 64 Klempnauer J. PP 227 Kuusniemi A.-M. OC 3 PP 371 Lukamowicz J. OP 41 Knapp W.H. PP 226 Kuwertz-Bröking E. Lee S.J. PP 81, PP 82 Lukeš A. PP 29 Kniewald H. PP 346 PP 171, PP 202 Lee S.K. PP 248, PP 400 Lunn A. PP 86 Knoers N.V.A.M. OP 40 Kwinta-Rybicka J. PP 70 Legato A. OP 14, PP 5, Lyons-Weiler J. OP 21 Knop M. PP 149 Kwon M.J. OP 37 PP 200 Mache C. OP 31 Knüppel T. PP 122 Kwon T. PP 249 Legendre F. PP 189 Mache C.J. PP 240 Ko J.K. PP 288 La Manna A. PP 93, Legnevall L. OC 9 Macher M.A. PP 180, Koepf S. PP 210 PP 96, PP 273, PP 274 Leichter H. OP 25 PP 249, PP 383 Pediatr Nephrol (2006) 21:1493–1635 1631

Madani A. PP 396 Mattyus I. PP 351 PP 395 Mutlu B. PP 111 Madrid A. PP 197, PP 198, Matyar S. PP 360 Moczulska A. PP 70 Mutlubas F. OP 13, PP 32, PP 199 Mavridis A.K. PP 359 Moeglich S. OP 7 PP 51, PP 247, PP 279, Magnetti F. OP 48 Maxwell H. PP 309, Mohceni P. PP 396 PP 387 Mahdavi A. PP 396 PP 310 Mohkam M. PP 30, PP 85, Mylrea K. PP 337, PP 338 Mahesh S. PP 246 Mayer A. PP 116 PP 276, PP 396 Nadal D. OP 18 Mair V. PP 122 Maytham D. PP 52 Molina C. PP 89 Nadalin S. OC 18, PP 4 Maisin A. OP 29, PP 222, Mazaheri M. PP 137 Molinos I. PP 317 Nadezhda S. PP 62 PP 249 McCulloch M.I. PP 52, Möller K. PP 25 Nagy A. OP 22 Makulska I. OP 10, PP 283 Molnár E. OC 15 Nahodkina I .V. PP 41 PP 330, PP 397, PP 405 MCCulloch V. PP 15 Mönch E. PP 181 Narciso V. PP 96, PP 274 Malaga S. PP 172 McIntoch I. PP 196 Monge M. PP 269 Nathanson S. PP 353 Malaventura C. OP 44 McKeever K. PP 153 Monge Zamorano M. Nau B. OP 56 Malec J. PP 159 McNeil E. PP 120 PP 270, PP 302 Navarro M. OP 27, PP 17, Malehorn D. OP 21 MedyĔska A. PP 46 Monnens L. PP 167, PP 185, PP 187 Malessy M.J.A. PP 95 Mehls O. OC 16, OP 52 PP 177, PP 254 Nee A.N. PP 264 Malgari G. PP 334 Mehrazma M. PP 27 Monnens L.A.H. PP 411, Negrisolo S. PP 16, PP 235 Malgieri G. OP 47, PP 382 Meichelbeck K. OC 15 PP 412 Neill E. PP 309, PP 310 Mallada L. PP 317, Meister M.G. PP 204 Monteverde M. OC 19 Neipp M. PP 225 PP 320, PP 321 Melek E. PP 245, PP 293, Montini G. OP 44, PP 101, Németh I. PP 380 Mallik M. PP 244 PP 341 PP 154, PP 186, PP 195, Nestrujeva V.V. PP 66 Malora B. PP 293 Melgosa M. OP 27, PP 187 PP 234 Neuhaus T. OP 25, OP 29 Mancini E. PP 110 Meliko÷lu M. PP 158 Montoya C. OP 25 Neuhaus T.J. OP 18, Mancuso D. OP 16, OP 45, Melmosa M. PP 185 Morais A. PP 17 PP 217, PP 403 OP 48 Mendelev N. OP 5 Morawiec –Knysak A. Nguyen T.Q.N. PP 242 Mangraviti S. OP 57 Mendes L. PP 239 PP 314 Ni L. OP 3 Manniello D. OP 45 Mengelle C. PP 242 Morel Y. PP 191 Niaudet P. OP 17, OP 28, Marabet E.L. OP 32 Mengoli C. PP 234 Morgan H.E.G. PP 324 PP 205, PP 223, PP 354, Marangella M. PP 145 Menouer S. OC 20 Morin D. PP 131, PP 189 PP 355 Marcelis C. OP 40 Meregalli E. PP 206, Morinière V. OP 39, Niemirska A. OC 10 Margieva T. PP 392 PP 216 PP 189 Nieto J. PP 197, PP 198, Maringhini S. PP 144, Merenmies J PP 38 Morooka M. PP 43, PP 99, PP 199 PP 145, PP 299, PP 404 Merkus M.P. PP 40 PP 381 Nikas J. PP 289 Markovic-Lipkovski J. Meseguer M. PP 187 Morris M.A. PP 134 Nikishina T. PP 345 PP 136, PP 236 Meseguer M.C. PP 185 Mosawi A.A. PP 142 Nikishina T.A. PP 66 Marks S.D. PP 203, Messina G. PP 312 Mosig D. OP 4 Nikolic-Bonaci B. PP 136 PP 204, PP 230 Messina M. PP 218 Motte J. PP 132 Nivet H. PP 189 Marra G. PP 49, PP 323, Michalk D. PP 340 Mougenot B. PP 251, Nižiü L.J. PP 346 PP 332 Michalkova K. PP 157 PP 353 Nobili F. PP 191 Marschitz I. PP 240 Michel-Calemard L. OC 8, Mourier O. OP 32 Noël L.H. PP 355 Martin X. PP 45 PP 175, PP 191 Moustafa N.O. PP 123 Norman M. OC 9 Martina V. PP 206, Miguel C. PP 155 Mraz M. PP 291, PP 292 Nourse P. PP 283 PP 213, PP 216 Miklaszewska M. PP 107, MS Goligorsky M.S. OP 5 Novakovic V. PP 47 Martinez Granero M.A. PP 109, PP 260, PP 328 Mueller-Wiefel D. OP 25 Novo R. OP 29, PP 222, PP 89 Milanovic S. PP 47 Müller D. OC 12, PP 301 PP 238 Martini S. OP 29, PP 122 Milenkovic T. PP 298 Müller V. OP 22 Nowicki M. OP 41, OP 46, Marzano L. OP 47, Milford D. OC 14 Müller-Wiefel D.E. PP 25, PP 396, PP 397 PP 336 Milford D.V. PP 372 PP 202 Noworolska D. OP 10 Massella L. OP 14, PP 200 Miloševiü D. PP 346 Mundel P. OP 7 Noyan A. OP 59, PP 7, Mastroyanni S. PP 289 Milosevski G. PP 290 Munier F. PP 134 PP 282, PP 360 Maternik M. PP 152 Minisini S. OC 2 Muorah M. PP 233 Nuutinen M. PP 38 Mathieson P.W. OC 4, Miorin E. PP 98 Muorah M.R. PP 230 Nuzzi F. OP 47, PP 382 OP 3, PP 15 Mir S. OP 13, PP 32, Murer L. OP 44, PP 16, O`Connell M. PP 228 Mathot R.A.A. PP 20 PP 51, PP 247, PP 279, PP 154, PP 186, PP 188, O’Riordan E. OP 5, Matkoviü M. PP 346 PP 282, PP 387 PP 195, PP 234, PP 235 PP 348 Matterassi M. PP 169 Mischak H. OP 30 Musante L. OP 57 O’Toole J.F. PP 164 Mattiello C. OC 7, PP 160, Misselwitz J. OC 19, Musavi S.H. PP 137 Oþenášková E. PP 29 PP 169, PP 206 OP 25, PP 202 Muscheites J. OP 55, Oellerich M. OP 23, Mattingley-Scott M. Missy P. OC 8, PP 175 PP 231 PP 221 OP 60 Mitrovic J. PP 121 Musial K. PP 335, PP 405 Offner G. OP 25, PP 119, Mattioli G. PP 398 Mitsioni A. PP 289, Mussa A. OC 13 PP 122, PP 224, PP 225, 1632 Pediatr Nephrol (2006) 21:1493–1635

PP 226, PP 227 Pape L. OP 25, PP 224, Piccoli A. OP 16 PP 298 Offner G.F. PP 210 PP 225, PP 226, PP 227 Pichault V. PP 45 Querfeld U. OC 12, Ogarek I. PP 70 Papp F. PP 285 Pichler G. OP 31 OP 25, PP 181, PP 211, Oh D. PP 182 Paradowski S. PP 112 Pichon B. OP 33 PP 301 Oh J. OP 7, PP 406 Parant O. OP 1 Piemonte F. PP 195 Quinlan C. PP 232 Oh J.M. PP 408 Parini R. PP 174 Pieper A.K. PP 211 Quintana M. PP 197, Oh T.K. OP 54 Paripovic D. PP 236, Pietrement C. PP 132 PP 198, PP 199 Okuyucu A. PP 333 PP 290 Pietrzyk J. PP 330 Raaijmakers R. PP 411, Olexa P. PP 291, PP 292 Park H.W. OP 54, PP 182, Pietrzyk J.A. PP 70, PP 412, PP 413 Oliveira A. PP 80 PP 376 PP 107, PP 109, PP 260, Rácz K. PP 380 Olsen O. PP 204 Park I.S. PP 288 PP 328, PP 397 Raddi G. PP 334 Oner A. PP 282 Park J.M. PP 36, PP 37, Pietuczuk M. PP 349 Radice L. PP 124 Onetti-Muda A. OP 36, PP 248, PP 252, PP 408 Pilecki W. PP 335 Ragab M. PP 325, PP 326, PP 195 Park Y.S. PP 133, PP 288, Pilie R. PP 118 PP 329, PP 339, PP 377 Orlova T.N. OP 5 PP 371 Pinello L. PP 186 Rajabnejad M. PP 85 Oráowska H. PP 92 Pascaud O. OC 8, PP 175 Pinto H.G. PP 42 Rakow A. OC 9 Örmälä T. PP 38 Pastore A. PP 195 Pinto P. PP 256 Ramaswami U. PP 174 Orrico A. PP 169 Patel B. PP 203 Pintos-Morell G. PP 174 Rambousek V. PP 364 Orsonneau J.L. OC 11 Patey-Mariaud de Serre N. Pintozzi L. PP 273 Ramelli G.P. PP 127 Ortaç E. PP 333 PP 223 Pissarra S. PP 80 Ramos-Trujillo E. PP 162 Orvos H. PP 146 Patricio J.P. PP 80 Plandsoen W.C.G. PP 95 Rampoldi L. PP 188 Osmanov I.M. PP 66 Patzer L. OP 34 Plank C. PP 210 Ranchin B. OP 12, Ostalska-Nowicka D. Paul A. OC 18, PP 4 Pluk W. PP 411, PP 412 PP 131, PP 180, PP 215, PP 369 Paulides M. OP 34 Podracka L. OP 53, PP 91, PP 222 OĞwiĊcimska J. PP 314 Pavone G. PP 117, PP 144, PP 291, PP 292 Randhawa P. OP 21 Otoukesh H. PP 27, PP 145, PP 299 Polak-Jonkisz D. PP 94, Rascher W. OP 25 PP 396 Pawelec M. PP 184 PP 335, PP 405 Rashid R. PP 309, PP 310 Otto E. PP 164 Peco-Antic A. OP 39, Polito C. PP 93, PP 96, Ratsch I. PP 117 Outeda P. PP 172 PP 236, PP 290 PP 273, PP 274 Ratsch I.M. PP 69 Ozaltin F. OP 15, PP 100, Pecoraro C. OP 47, PP 48, Poltavets N. OP 43 Raymond P. PP 118 PP 243, PP 347, PP 391 PP 117, PP 128, PP 334, Póátorak-Krawczyk A. Rea M. PP 93, PP 96, Özcakar Z.B. PP 253, PP 336, PP 382, PP 404 OP 41 PP 274 PP 259, PP 407 Pelikan R. OP 21 Polykov A. OP 43 Rees L. OC 14, PP 207, Ozcay F. PP 341 Pelkowska A. PP 70 Ponikvar R. PP 108, PP 233, PP 306, PP 307 Ozdemir N. PP 55, PP 58, Pellantova Z. PP 364 PP 113, PP 308 Refaat G.A. PP 123 PP 275 Peña A. OP 27, PP 172, Popova V.V. PP 264 Regueras L. PP 26 Özden N. PP 119 PP 187 Porowski T. PP 126 Reid C. PP 233 Özen A. PP 275 Pennaforte T. PP 238 Porta F. OC 13 Reid C.J.D. OP 33 Özen S. OP 15, PP 53, Pennesi M. OC 2 Pota A. PP 48, PP 128, Rejtar P. PP 28, PP 151 PP 100, PP 261, PP 284, Penza R. PP 61, PP 63, PP 334 , PP 336 Rémésy M. PP 242 PP 295, PP 347, PP 389 PP 193 Potocekova D. PP 91, Reusz G. OP 22, PP 212 Ozgul K. PP 347 Perahud I. PP 370 PP 291, PP 292 Reusz G.S. PP 351 Ozgur E. PP 296, PP 297 Peratoner L. OC 2 Poyrazoglu H.M. PP 150, Rezvani M.R. PP 137 Özkaya O. PP 57, PP 111, Perepyolkina N. PP 44 PP 178, PP 267 Rguez do Forno A. PP 333, PP 399, PP 410 Perfumo F. OP 57, Prasad N. PP 344 PP 172 Ozmen M. OP 15 PP 235, PP 398, PP 404 Premru V. PP 308 Ribeiro M.d.C. PP 80, Ozpoyraz H. PP 282 Perrin L. PP 352 Prévot A. OP 4 PP 155, PP 256 Pacenti M. PP 234 Perrotta S. PP 186 Prikhodina L. OP 43, Ricotti E. PP 218 Paglialonga F. PP 49 Persy V. PP 301 PP 345, PP 357 Ricotti M. OP 45 Paik K.H. PP 400 Peru H. PP 143 Prikhodina L.S. PP 66 Ridout D. PP 306 Paize F. PP 286 Peruzzi L. OP 16, OP 36, Prinza N. PP 73 Rigamonti W. PP 16, Palma E. PP 93 OP 45, OP 48 Proietti E. OP 36 PP 154 PaĔczyk-Tomaszewska M. Petaccia A. OP 36 Prokurat S. PP 330 Rigden S.P.A. PP 21, PP 65 Petrarulo M. PP 110, Prüfer F. PP 122 PP 135 Panyutina Y.V. PP 23 PP 145 Puczko-Michalczuk A. Rijk Y. PP 413 Papachristou F. PP 73 Petrosyan E.K. PP 386 PP 163 Ring E. OP 31, PP 240 Papadopoulou F. OP 2, Petrovic – Tepic S. PP 47 Pugh P. PP 244 Rink N. PP 25 PP 79, PP 359 Peuchmaur A. PP 383 Puretiü Z. PP 346 Robbe W.J. PP 95 Papaleo A. PP 138 Peuchmaur M. OP 32 Puricelli E. PP 160 Robieux I. PP 98 Papalia T. PP 266 Picca M. PP 49 Puteo F. PP 312 Rocha de Barros V. PP 241 Papayan K.A. PP 23 Picca S. PP 110 Putnik J. PP 115, PP 136, Rodenbeck B. PP 148, Pediatr Nephrol (2006) 21:1493–1635 1633

PP 149 Sandoval M. PP 323, Sekerel B. PP 389 Slack M. OP 33 Rodl S. OP 31 PP 332 Sekowska R. PP 88 Sladowska E. OP 52 Rodrigo Jiménez M.D. Santangelo G. PP 144 Selvaggio G. PP 332 Sladowska J. OC 10, PP 268, PP 270, PP 302 Santorelli F.M. PP 195 Semeshina O.V. PP 264 PP 316, PP 327 Rodríguez J. PP 130, Santoro C. PP 93, PP 96, Sener G. PP 6, PP 9 Slaný J. PP 75 PP 317, PP 319, PP 320, PP 274 Serdar A. PP 47 Slowiaczek E. PP 70 PP 321 Santoro M. OP 39 Sereni F. PP 323, PP 332 Smakal O. PP 157 Rodríguez L.M. PP 26 Santos F. PP 130, PP 317, Sergeeva T. PP 303, Smirnov I. PP 303 Rodríguez-Palmero A. PP 319, PP 320, PP 321 PP 366, PP 392 Smith W. PP 309 PP 174 Sapia M.C. PP 144, Sever L. OP 59 Smokvina A. PP 90 Roedl S. PP 240 PP 145, PP 299 Seydaoglu G. PP 7 Smoljanic Z. PP 236 Roemer W. PP 254 Sapunar D. PP 14 Shaheen I. PP 116 Smrcka V. PP 364 Roloff S. PP 181 Saraga M. PP 14, PP 365 Shanlin C. OP 6 Sobczyk D. PP 97, PP 192 Rombis V. PP 73 Saraga-Babic M. PP 14, Sharifian M. PP 30, PP 85, Sobieszczanska M. PP 335 Ronco P. PP 367 PP 365 PP 276, PP 396 Sohn S. PP 60 Ronkainen J PP 38 Sarago M. PP 346 Sharma R.K. PP 344 Soleimani G.R. PP 67 Rossi R. OP 34 Saraymen R. PP 333 Shatat I.F. OP 5, PP 348 Sommer K. OC 12 Roszkowska-Blaim D. Sarhan A. PP 325, PP 326, Shatochina O.V. PP 66 Song J.H. PP 390 PP 330 PP 339, PP 377 Shestakov A.E. PP 386 Song J.S. PP 390 Roszkowska-Blaim M. Sarioglu S. PP 2, PP 3 Shim Y.H. PP 81, PP 82 Sonmez F. OP 59, PP 247 PP 65, PP 88, PP 92, Saunier S. PP 189 Shin J.I. OP 37, PP 36, Soran M. PP 7, PP 360 PP 342, PP 397 Sauvat F. PP 205 PP 37, PP 248, PP 252, Sorino P. PP 312, PP 404 Roussel B. PP 132 Savage J.M. PP 153 PP 408 Soukalo A.V. PP 104 Roussey G. PP 222 Savane L. PP 52 Shin Y.H. PP 248 Sousa R. PP 42 Roussey-Kesler G. OC 11 Savenkova N.D. PP 23, Shroff R. OC 14, PP 207 Soy D. PP 259 Roze J.C. OC 11 PP 41, PP 161 Siamopoulou A. PP 359 Soylemezoglu O. PP 72, Rtskhiladse I. PP 374 Savo D. PP 49 Siamopoulou-Mavridou A. PP 143, PP 296, PP 297 Rubik J. PP 260 Sayer J.A. PP 164 OP 2 Soylu A. OP 59, PP 2, RudziĔski A. PP 328 Saygili A. OP 59 Siapera D. PP 395 PP 3, PP 33, PP 77, Ruffo G.B. PP 145 Scalacci E. OP 51 Sikatchev A. PP 303 PP 156, PP 261, PP 282 Runowski D. PP 35, Scalamogna M. PP 235 Sikora P. PP 265 Sözeri B.Y. PP 387 PP 184 Scavia G. PP 117 Silipigni L. PP 59, PP 84, Spajiü M. PP 346 Rus R. PP 108, PP 113 Schaefer F. OC 16, OC 19, PP 304 Sparks E.E. PP 11 Rusai K. PP 212 OP 39, OP 56, OP 58, Silva Galan Y. PP 332 Spasojevic B. PP 236, Rüth E.M. PP 403 OP 60, PP 148, PP 149, Silva M.J. PP 155 PP 290 Rychlik I. PP 364 PP 406 Simao C. PP 239 Spurny P. PP 291, PP 292 Ryoo E. PP 34 Schäfer J. OP 58 Simkova E. OP 26, PP 39, Staffolani F. PP 69 SabasiĔska A. PP 78 Schanstra J.P. OP 30 PP 257, PP 287 Stajic N. PP 115, PP 136, Sabot J.F. PP 45 Schechner R. PP 246 Simonetti G.D. PP 127, PP 298 Sadallah S. PP 370 Scheiring J. PP 122 PP 280, PP 281 Stanic M. PP 236, PP 290 Sadeghi Bojd S. PP 129 Schell-Feith E.A. PP 31 Simsek M.B. PP 7 Stankiewicz R. PP 330, Saïd M.H. PP 215 Schiavone S. OP 51 Sinclair P. PP 52 PP 397 Saina G. PP 90 Schifferli J. PP 370 Sindicic N. PP 373 Stapenhorst L. PP 179, Sakalli H. PP 293, PP 341 Schmidt S. OC 12 Sinha M. OP 24 PP 229, PP 340 Sakallioglu O. PP 100 Schmitt C.P. OP 56, Sinha M.D. PP 135 Starha J. PP 364, PP 384 Salagovic J. PP 91 OP 58, OP 60 Siomou E. OP 2, PP 79, Stec Z. PP 70 Salata M. PP 117 Schnaper H.W. PP 11 PP 359, PP 395 Stefaniak E. PP 330, Saleem M.A. OC 4, OP 3, Schröder C.H. PP 411, Sirico M.L. PP 48, PP 128, PP 397 PP 15 PP 412, PP 413 PP 334, PP 336 Stefanidis C.J. OP 2, Salera S. PP 49 Schuett B. OP 7 ùirin A. PP 250, PP 261, PP 289, PP 395 Sallay P. PP 351 Schulze Everding A. PP 282 Steines J. PP 406 Salomon R. OP 39, PP 138, PP 202 Siten G. PP 330 Stejska J. PP 159 PP 180, PP 189, PP 205, Schwarz A. PP 227 SiwiĔska A. PP 97, Stejskal J. PP 257, PP 364 PP 223, PP 354, PP 355 Šüukanec-Špoljar M. PP 192, PP 369 Stöhr W. OP 34 Salviati L. OP 44, PP 186 PP 346, PP 365 Sixt R. OP 20 Stokland E. OP 20 Samardzic – Predojevic J. Šebeková K. OP 53 Škába R. PP 75 Stoksik P. PP 314 PP 47 Sebire N.J. PP 230 Skálová S. PP 28, PP 29, Stone R. OP 16 Sampaio S. PP 42 Seeman T. OP 26, PP 39, PP 151, PP 364 Storry C. OC 14 Sancak T. PP 253 PP 257, PP 287 Skibova J. PP 364 Strambi M. OP 51 Sancewicz-Pach K. PP 70 Segoloni G. PP 218 Skitareliü N. PP 346 Strazdins V. PP 87 Sandberg J. PP 208 Seikku P. PP 219 Skorupa E. OC 10 Strehlau J. PP 227 1634 Pediatr Nephrol (2006) 21:1493–1635

Stringini G. OP 36, PP 5 Titov L. PP 370 Tverskay S. OP 43 Vavrinec J. OP 26, PP 39 Strompf L. PP 176 Tkaczyk M. OP 41, OP 46, Tydén G. PP 208 Vaz R. PP 256 Stucchi S. PP 124 PP 397 Tzygin A.N. PP 386 Vega M.I. PP 209 Šubat-Dežuloviü M. Tobaldi R. PP 69 Ubetagoyena M. PP 172 Vega-Hernández M.C. PP 90, PP 346, PP 373 Toffolo A. PP 101 Uçar Y. PP 259 PP 162 Šufliarsk S. PP 64 Tokel K. PP 245 Ulinski T. PP 103, PP 201, Veinberg F. PP 103 Sukalo A. PP 370 Tolunay O. PP 72 PP 251, PP 352, PP 353, Velioglu-Ogunc A. PP 6 Sukhai R.N. PP 95 Tomaskova H. PP 384 PP 363 Verberckmoes S.C. Sukhanov A. OP 49 Tomasoni L. PP 213 Umemura K. PP 43, PP 301 Šuláková A. PP 75 Tönshoff B. OC 17, OP 7, PP 381 Verebova M. PP 91 Šuláková T. PP 75 OP 23, OP 25, PP 122, Unal B. PP 245 Vernì M. OC 1 Sulyok E. PP 106 PP 210, PP 211, PP 220 Uncu N. PP 253, PP 259, Verrina E. OP 57, PP 117, Sümegi V. OC 15, PP 146, PP 221 PP 261 PP 398, PP 404 PP 379 Topaloglu R. OP 15, Unlu M. PP 296 Vester U. OC 18, PP 4 Sumnik Z. PP 257 PP 53, PP 100, PP 243, Urbina C. PP 323 Vethamuthu J. PP 237 Sun M. OP 21 PP 284, PP 295, PP 347, Uria C. PP 209 Veyradier A. PP 251 Sun Y.H. PP 34 PP 389 Urisarri A. PP 172 Veysseyre C. OP 12 Sung M. PP 60 Torre M. PP 398 Uslu Y. PP 196, PP 245, Vezzoli G. PP 169 Swerkersson S. OP 20 Tortola T. PP 199 PP 293, PP 341 Viana M. PP 89 ĝwiątkowska E. OP 41 Toth-Heyn P. PP 351 Usluer H. PP 76 Viganò S. M. PP 213, Syrèn M.L. OC 7, PP 169 Tovo P.A. OP 45 Utsch B. PP 171 PP 216, PP 323, PP 332 Syrrou M. OP 2 Tozzi A.E. OP 36, PP 117 Vachvanichsanong P. Viklický O. PP 212 Szabo A.J. OP 22, PP 212 Tran S. PP 12 PP 120 Vila A. PP 197, PP 198, Szabó L. OC 15 Trautmann A. PP 148 Valbuena C. PP 42 PP 199 Szakal O. PP 258 Travan L. OC 2 Valenciano B. PP 172 Vilalta R. PP 197, PP 198, SzczepaĔska M. PP 314, Travi M. PP 169 Valentini N. PP 93, PP 96, PP 199 PP 330 Trendelenburg M. PP 370 PP 273 Vilits P. PP 240 Szmigielska A. PP 88 Trimoreau F. PP 375, Vallo A. PP 172 Visch H.J. PP 177 Szolnoki J. PP 351 PP 378 Van Damme-Lombaerts R. Vissy M. OC 15 Szprynger K. PP 314 Trivelli A. PP 398 OP 29 Vítko S. PP 212 Tabel Y. PP 279 Tromp W.F. PP 119 Van de Kar N.C.A.J. Vivarelli M. PP 5 Tafuro L. OC 1, PP 96, Trompeter R. PP 233 PP 413 Vlþková H. PP 75 PP 273 Trompeter R.S. OC 5, Van den Heuvel L. von Baum H. PP 406 Takacs J. PP 91 PP 54, PP 207, PP 230 PP 167, PP 177, PP 254 von Unruh G.E. PP 265 Tálosi G.Y. PP 380 Trouet D. OP 3 Van den Heuvel L.P.W.J. von Vigier R. PP 280 Tammaro F. PP 61, PP 63 Tsakas K. PP 73 PP 411, PP 412 von Vigier R.O. PP 127 Tan O. PP 72 Tsimaratos M. OP 17, van der Heijden A.J. Vondrak K. OP 26, PP 39, Tangerman A. PP 166 OP 29, PP 10, PP 180 PP 31 PP 257, PP 287 Taque S. PP 180 Tsygin A. OP 49, PP 303, van der Plas R.N. PP 95 Vosoug P. PP 22 Tassi R. OP 51 PP 361, PP 366, PP 392 Van Dessel E. PP 71 Vosough P. PP 24 Taupin P. OP 28 Tugay S. PP 76, PP 141, Van Dugteren G. PP 52 Voznesenskaya T. PP 366 Tavaré J. OC 4 PP 294, PP 388 van Gool J.D. PP 71 Vrljiþak K. PP 346 Tavil B. PP 102 Tugtepe H. OP 9, PP 6, Van Hoeck K. PP 71 Vukanic D. PP 236 Taylor C.M. OP 33, PP 8, PP 9 Van Kan H.J.M. PP 214 Vukic-Kosuljandic D. PP 255, PP 372 Tugyan K. PP 2 Van Renthergem D. PP 71 PP 365 Taylor J. OP 24, PP 233 Tulassay T. PP 212 van Rossum L.K. PP 20 Vulto A.G. PP 20 Tchah H. PP 34 Tullus K. OP 33 van Zwieten P. PP 31 Vusurovic V. PP 121 Tedeschi S. OC 7, PP 169 Tunaoglu S. PP 297 Vanadia F. PP 144 Vyalkova A. PP 44, Teixeira P. PP 155 Tung D.K. OP 4 Vande Walle J. OP 29 PP 361, PP 362 Tejera P. PP 162 Tur I. PP 62 Vaníþek H. PP 29 Waldherr R. PP 211, Tellis V. PP 246 Tur N. PP 370 Vanny A. OP 22 PP 374 Temel E. PP 296, PP 297 Turcato S. PP 218 Vanpee M. OC 9 Waldron M. PP 228, Terzic J. OC 20 Túri S. OC 15, PP 146, van't Hoff W. OP 33, PP 232 Tesar V. PP 364 PP 285, PP 379, PP 380 OP 35 Wallace A.M. PP 309, TesaĜová M. PP 159 Turiel M. PP 213 Varan B. PP 245 PP 310 Thamnopoulos C.H. PP 73 Turkmen M. PP 2, PP 3, Varda N.M. OP 11 Waller S.C. PP 306, Thomas D. PP 116 PP 33, PP 77, PP 156 Vargas-Poussou R. PP 307 Thomas D.F.M. PP 168, Türkyılmaz Z. PP 33 PP 176, PP 190 Waloschek T. PP 75 PP 173 Turpitko O. PP 345 Varol E. PP 389 Walther F. PP 31 Tichy T. PP 157 Turpitko O.J. PP 66 Varshavsky V. PP 357 Wanke R. OP 7 Tirelli S. PP 206 Turtinen J. PP 38 Vats A. OP 21 Warady B. OC 19 Pediatr Nephrol (2006) 21:1493–1635 1635

Warnier M. PP 254 PP 55 Zucchini A. PP 188 Warzywoda A. PP 331 Yilmaz A. PP 250 Žugiü R. PP 308 Wasilewska A. OP 42, Yilmaz B.T. PP 196 Zurowska A. OC 19, PP 78, PP 126, PP 163, Yilmaz H. PP 250 OP 56, PP 152, PP 262, PP 349 Yilmaz O. PP 3 PP 330, PP 397, PP 409 Waters A. OP 33 Yoon S.J. PP 408 Zwierz K. PP 126, PP 163 Watson A. OC 14, PP 86, Yousefi S.H. PP 27 ZwoliĔska D. OP 10, PP 116, PP 244 Yuksel M. PP 9 PP 46, PP 94, PP 335, Wawer Z.T. OC 10 Yüksel S. PP 253, PP 407 PP 397, PP 405 Wawro A. PP 46 Yun K.W. PP 83 Weber L.T. OP 23, Zaccaria I. OC 8, PP 175 PP 125, PP 210, PP 220, Zacchello G. OP 44, PP 221 PP 16, PP 101, PP 154, Weber S. PP 149, PP 368 PP 186, PP 188, PP 234, Weitzel D. OP 48 PP 235, PP 404 Welsh G.I. OC 4 Zachwieja J. PP 97, WeryĔski P. PP 109 PP 192, PP 331, PP 369, Wiercinski R. PP 330, PP 397 PP 397 Zachwieja K. PP 107, Wierzbicka A. OC 10 PP 109, PP 260, PP 328, Wiggelinkhuizen J. PP 52 PP 397 Wigger M. OP 55, PP 231 Zagozdzon I. PP 330, Wilkosz K. PP 70 PP 397, PP 409 Willems J.L. PP 411, Zahrane M. PP 123, PP 412 PP 300, PP 313 Willems P. PP 177 Zajączkowska M. PP 265, Willi U. OP 18 PP 397 Wilmer M. PP 177 Zaklyazminskaya E. Wingen A.M. OC 18, PP 4 OP 43 Witt M. PP 369 Zalewski G. OP 42 Wittke S. OP 30 Zaluska-Lesniewska I. Wojnar J. PP 65, PP 88 PP 262 Wolf M. PP 229 Zangurashvili L. PP 374 Wolf E. OP 7 Zaniew M. PP 97, PP 192, Wolf M.T.F. PP 179 PP 331, PP 369 Wolterbeek R. PP 31 Zdravkovic D. PP 298 Wong H. PP 337, PP 338 Zebger-Gonga H. OC 12 Woods V. PP 15 Zenker M. PP 159 Woolf A. PP 168, PP 173 Zhang S.L. PP 12 Woroniecki R.P. OP 5, Zhu Y.H. PP 12 PP 348 Zimmerhackl L.B. OP 25, Wühl E. OC 16, OP 39, PP 122, PP 210, PP 368 OP 52, PP 211, PP 406 Zimmering M. OC 19 Würzner R. PP 122 ZimoĔ T. PP 112 Wygoda S. OP 25, OP 39 Ziolkowska H. PP 65, Xiaochuan W. PP 206 PP 330, PP 342 Yalçınkaya F. PP 253, Ziora K. PP 314 PP 259, PP 261, PP 282, Zipfel P. PP 122 PP 407 Zivanovic S. PP 298 Yamamoto Y. PP 43, Zobel G. OP 31 PP 99, PP 381 Zoch-Zwierz W. OP 42, Yang D. OP 22 PP 78, PP 163, PP 349, Yavaúcan O. PP 32, PP 397 PP 247, PP 279, PP 387 Zoch-Zwierz W.M. Yegen B.C. PP 6, PP 9 PP 126 Yehia S. PP 329 Zolfigol A. PP 350 Yeniay B.S. PP 32, PP 51, Zonderland H.M. PP 31 PP 247, PP 279 Zorin I. PP 44, PP 361, Yildiz B. PP 263, PP 385, PP 362 PP 394 Zucca C. PP 124 Yildiz N. OP 59, PP 33, Zucchetta P. PP 154