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see commentary on page 17 3–5 year longitudinal follow-up of pediatric patients after acute renal failure DJ Askenazi1, DI Feig1,2, NM Graham3, S Hui-Stickle1, SL Goldstein1,4

1Department of Pediatric Nephrology, Baylor College of Medicine, Houston, Texas, USA; 2Director of Pediatric Hypertensive Clinic, Baylor College of Medicine, Houston, Texas, USA; 3Dialysis Unit, Texas Children’s Hospital, Houston, Texas, USA and 4Director of Unit, Texas Children’s Hospital, Houston, Texas, USA

Few data exist regarding the long-term sequelae of acute Acute renal failure (ARF) is defined as the abrupt inability of the renal failure (ARF), and these studies are limited to a few kidneys to eliminate waste products and regulate electrolyte/ renal conditions. We aim to assess the 3–5-year survival and water metabolism. Patients who suffer an ARF episode may incidence of renal injury in children who previously have subsequent renal dysfunction after the original injury, and developed ARF of varying causes. We queried parents, children may be more susceptible to this injury due to the physicians, and hospital/state vital statistics records to find ongoing growth of the during childhood. Some data that patient survival in 174 children who previously had ARF and describe long-term renal sequelae in children who had ARF due survived to hospital discharge. We assessed the following in to congenital heart ,1 Henoch–Schonlein purpura,2 very 29 children for residual renal injury: (a) microalbuminuria, (b) low birth weight neonates,3 and hemolytic uremic syndrome glomerular filtration rate (GFR) by Schwartz formula, (c) exist.4 Persistent microalbuminuria is common in women 3–5 , and (d) . The 3–5-year survival of years after a pre-eclampsia episode.5 Studies in adults6 have children with ARF who survived to hospital discharge was found ongoing renal injury after ARF of multiple etiologies, but 139/174 (79.9%). Most deaths (24/35 (68.5%)) occurred these studies may not be extrapolated to children, since adults within 12 months after initial hospitalization. Combining demonstrate higher rates of comorbid illnesses than children. those who died during initial hospitalization and in In the 1980s, intrinsic renal and burns comprised the subsequent 3–5 years, the overall survival rate was 139/245 most common pediatric ARF etiologies.7–13 A recent study (56.8%). In all, 16 children progressed to end-stage renal performed in our institution between January 1998 and disease; thus, renal survival was 127/173 (91%). Those with December 2001 found that the epidemiology of pediatric primary renal/urologic conditions had lower renal survival patients with the diagnosis of ARF has broadened over the last than others (24/35 (68.6%) vs 134/139 (96.4%); Po0.0001). decade.14 Now, pediatric ARF most often results from Among the 29 patients assessed for long-term sequelae at complications of other systemic diseases resulting from the 3–5 years, 17/29 (59%) subjects had at least one sign of renal advancements in congenital heart surgery, neonatal care, and injury; microalbuminuria (n ¼ 9), hyperfiltration (n ¼ 9), marrow and solid organ transplantation. That study decreased GFR (n ¼ 4), and hypertension (n ¼ 6). A pediatric showed that 174/245 (71%) patients survived the initial nephrologist was involved in care of only 6/17 (35%) with hospitalization. At hospital discharge, 68% of survivors chronic renal injury. Patients have high risks of ongoing recovered complete renal function, 13% had improved renal residual renal injury and death after ARF; therefore, periodic function, 12% sustained renal failure, and 5% progressed to evaluation after the initial insult is necessary. end-stage renal disease (ESRD). Determining the natural history Kidney International (2006) 69, 184–189. doi:10.1038/sj.ki.5000032 following an ARF episode will help clinicians design appropriate KEYWORDS: acute renal failure; renal survival; long-term survival; chronic monitoring programs. If renal injury is common, therapeutic renal injury; microalbuminemia; hypertension interventions to prevent progression of renal injury can be sought. In order to assess the long-term outcome of children with a variety of ARF causes, we conducted a follow-up study to determine patient and renal survival, to look for signs of kidney injury, and to assess the health-related quality of life of the original cohort. To our knowledge, this is the first analysis to describe the long-term outcome of children after ARF.

Correspondence: DJ Askenazi, Department of Pediatric Nephrology, RESULTS University of Alabama at Birmingham, 1600 7th Avenue South, ACC 516, Epidemiology Birmingham, Alabama, 35322, USA. E-mail: [email protected] Initial hospital survival. The hospital survival after an ARF Received 29 April 2005; revised 24 June 2005; accepted 11 August 2005 episode at Texas Children’s Hospital between January 1998

184 Kidney International (2006) 69, 184–189 DJ Askenazi et al.: Follow-up of children after ARF original article

Table 1 | Survival in children after ARF

Ren/Uro All Patients No ICU ICU Initial RRT No initial RRT comorbid No Ren/Uro

Hospital survival 174/245 (71.0%) 65/66 (98.5%) 109/179 (60.9%) Po0.001 44/75 (58.7%) 130/170 (76.5%) Po0.01 35/37 (94.6%) 139/208 (66.8%) Po0.001 3–5-year survival of 139/174 (79.9%) 54/65 (83.0%) 85/109 (78.0%) NS 31/44 (70.5%) 108/130 (83.1%) NS 31/35 (88.6%) 108/139 (77.7%) NS hospital survivors Renal survival 158/174 (90.8%) 56/65 (86.1%) 102/109 (93.6%) NS 37/44 (84.1%) 121/130 (93.1%) NS 24/35 (68.6%) 134/139 (96.4%) Po0.0001 Ren, renal; RRT, renal replacement therapy; Uro, . and June 2001 was 174/245 (71%). Patients who required 245 children with ARF at TCH renal replacement therapy (RRT), intensive care unit (ICU) January 1998 − June 2001 admission, and those without primary renal/urologic condi- 71 did not survive 174 survived tions were less likely to survive hospitalization (Table 1; data 14 from Hui-Stickle et al. ). 32 died after discharge 16 ESRD 126 potential subjects Survival at 3–5 years of initial hospital survivors. The 3–5- Parent or MD report year survival rate for the children with ARF who survived to hospital discharge was 139/174 (79.9%). No survival dif- 3 Died 69 Unable to locate 28 Did not show or ference was seen for patients with ICU admission vs without 13 Alive ICU admission, receiving initial RRT vs not receiving initial refused RRT, or renal/urologic vs no renal/urologic comorbidity 29 Subjects (Table 1). Of the 35 deaths that occurred after initial hospital Figure 1 | 3–5-year outcomes of children who developed ARF at discharge, 24/35 (68.5%) occurred within 12 months and 31/35 Texas Children’s Hospital between January 1998 and June 2001. (88.6%) occurred within 24 months after initial hospitalization. In total, 29 subjects were further evaluated for signs of chronic renal injury. Renal survival. Of the initial hospital survivors, at least 16 children progressed to ESRD (three of these have died); thus, the renal survival at 3–5 years was 158/174 (90.8%). ESRD Table 2 | Demographics of potential participants occurred more commonly in patients with primary renal/ Came Did not come urologic conditions vs others (24/35 (68.6%) vs 133/139 (n=29) (n=97) (95.7%); Po0.0001). Neither ICU admission nor the initial Age at hospital admission 6.475.8 6.476.5 NS need for RRT was predictive of long-term renal survival. Age at follow-up 9.876.5 12.177.2 NS Years after event 3.770.9 4.171.1 NS Renal injury Ethnicity NS Patient population. In all, 119/245 of the original cohort Caucasian 11 (38%) 35 (36.1%) were known to have either (a) ESRD or (b) died during or Hispanic 10 (34%) 27 (27.9%) after hospitalization; thus, 126 children were available for African American 6 (21%) 27 (27.9%) Asian 0 (0%) 4 (4.1%) renal injury assessment. Also, 69 subjects did not respond by Other 2 (7%) 4 (4.1%) phone or mail and 28 subjects refused to participate. Reasons No. of male patients 13 (44.9%) 57 (58.8%) NS for refusal included: ‘too busy’ (n ¼ 8), ‘adequate follow-up’ RRT 6 (20.7%) 20 (20.6%) NS (n ¼ 3), ‘too hard’ (n ¼ 2), ‘live too far’ (n ¼ 1), refused to Hypertensive at the time of ARF 9 (31.0%) 27 (27.8%) NS give a reason (n ¼ 3), and did not show (n ¼ 11). We output at the time of ARF 3.073.5 2.672.2 NS evaluated 29/126 (23%) of potential subjects for signs of (ml/kg/h) GFR minimum (ml/min/1.73 m2) 25.7719.2 26.1720.4 NS renal injury and health-related quality of life between Length of stay (days) 18.6721.5 12.8733.3 NS February and July 2004 (Figure 1). No. of patients with primary 10 (34.4%) 12 (12.4%) Po0.01 Participants in the study and those who were lost or renal/urologic conditions refused to participate in the study did not differ with regard No. of patients requiring ICU stay 17 (58.6%) 64(64.3%) NS to demographics, length of stay, frequency of ICU hospita- Outcome at discharge (no. of patients) NS lization, severity of renal failure, and outcome at the time of Normal 21 (72.4%) 67 (69.1%) Improve 6 (20.7%) 18 (18.6%) discharge. In all, 6/29 (20.6%) subjects evaluated for follow- CRF 2 (6.8%) 12 (12.3%) up required RRT and 17/29 (56.3%) were ICU patients Cause of renal failure (no. of patients) NS during the initial hospitalization. Those with primary renal/ Nephrotoxic 3 (10.3%) 15 (15.5%) urological disease were more likely to participate in the study Atn/sepsis/hemorrhage 11 (37.9%) 35 (36.1%) than those without primary renal comorbidity (10/29 Cardiac 3 (10.3%) 14 (14.4%) (34.4%) vs 12/97 (12.4%); P 0.01) (Table 2). Oncologic 2 (6.9%) 7 (7.2%) o Hemoglobin/myoblobinuria 1 (3.4%) 3 (3.1%) Signs of renal injury. Of the 29 patients in our study, 17/29 Primary renal 4 (13.8%) 9 (9.3%) (59%) had at least one sign of renal injury. One patient had 0 (0.0%) 3 (3.1%) abnormalities in all four indices and eight had abnormalities Unknown 5 (17.2%) 11 (11.3%)

Kidney International (2006) 69, 184–189 185 original article DJ Askenazi et al.: Follow-up of children after ARF

Table 3 | Signs of renal injury 3–5 years after ARF episode GFR at follow-up Spot urine Follow-up No. Subject no. Overall BP (ml/min/1.73 m2) GFR outcome Alb/Cr Microalbumin Hematuria by renal abnormal 1 H* 118.4 N 402.1 Yes No Yes 2 2 N 109.0 N 59.5 Yes No No 1 3 N 177.5 H 22.8 No No Yes 1 4 N 166.3 H 52.3 Yes No No 2 5 H 182.0 H 6.3 No No No 2 7 N 199.0 H 96.6 Yes No Yes 2 11 H* 31.1 L 256.6 Yes Yes Yes 4 13 N 86.2 L 25.5 No No No 1 14 N 219.3 H 53.2 Yes No No 2 16 H 66.7 L 11.9 No No Yes 2 18 N 295.9 H 48.7 Yes No No 2 19 H 111.6 N 7.5 No No No 1 21 N 49.2 L 98.9 Yes No No 2 23 H 117.4 N 23.9 No No Yes 1 26 N 187.2 H 18.4 No No No 1 28 N 169.1 H 10.8 No No No 1 29 N 185.5 H 10.2 No No No 1 Total=17 HTN=6 CRF stage 1=9 Microalbumin=8 Hematuria=1 Renal F/U=6 CRF stage 2=4 Two patients (*) on antihypertensives for BP control. CRF stage 1: ClCr X150 mg/min/1.73 m2. CRF stage 2: ClCr o90 mg/min/1.73 m2. Microalbuminuria: spot urine alb/cr X30. H, high; HTN, hypertension; L, low; N, normal.

Table 4 | GFR vs microalbuminuria CRF Normal Hyperfiltration (CClo90 ml/min/1.73 m2) (90oCCl 4150 ml/min/1.73 m2) (CCl4150 ml/min/1.73 m2) Total Normal urine albumin/ 2 14 5 21 Microalbuminuria urine Alb/Cr430 2 2 4* 8 Total 4 16 9 29 *P=0.02 vs. normal. in two markers. The proportion of children who had at least Hematuria. Only one patient had microscopic hematuria. one sign of renal injury was similar between those who had This patient also had hypertension, microalbuminuria, and primary renal/urologic conditions compared to those with- chronic renal failure. out renal/urologic conditions (5/10 (50%) vs 11/19 (57.9%); Hypertension. Six patients were found to be hypertensive: NS). Only 6/17 (35%) patients who had signs of renal injury four patients had hypertension as defined by the fourth in at least one domain had follow-up with a pediatric report on pediatric hypertension by repeat clinic blood nephrologist at the time of the study (Table 3). pressure measurement. Although four patients were pre- Glomerular filtration rate (GFR). At the time of follow-up, scribed antihypertensive , only two were for the average GFR by Schwartz formula was 137.9752.9 ml/min/ blood pressure control, one for tachycardia, and one for 1.73 m2 (range 31.1–295.9 ml/min/1.73 m2). We found nine after-load reduction. children with stage 1 chronic (hyperfiltration as We found no correlation between hypertension and defined by Schwartz formula creatinine clearance (CCl) microalbuminuria or GFR. Hypertension, urine output, 4150 ml/min/1.73 m2) and four children with chronic kidney and degree of renal failure (nadir GFR) during initial disease stage 2 (CCl by Schwartz formula o90 ml/min/1.73 m2). hospitalization were not predictive of hypertension, micro- Microalbuminuria. The mean spot urine albumin/creati- albuminuria, and abnormalities in GFR at the time of follow- nine ratio was 46.2784.7 (range ¼ 4.1–402.1). Eight patients up in our cohort of patients. had microalbuminuria (urine albumin/creatinine430). Of the patients who required RRT during the initial Microalbuminuria was more common in patients who had episode of ARF, 4/6 children had signs of renal injury at the stage 1 compared to those with time of follow-up (two had hyperfiltration and four had normal GFR (Po0.02) (Table 4). Of the eight patients with hyperfiltration and microalbuminuria). microalbuminuria, seven had at least one other marker of renal injury. The one patient who solely had microalbumi- Quality of life nuria was a patient with acute lymphocytic leukemia who did By performing PedsQLTM 4.0, we found no difference between not have primary urologic or renal disease. children with ARF compared to healthy population.

186 Kidney International (2006) 69, 184–189 DJ Askenazi et al.: Follow-up of children after ARF original article

DISCUSSION as hemolytic–uremic syndrome, can lead to hypertension, To our knowledge, this is the first analysis that evaluates the microalbuminuria, and chronic renal failure. Our study longitudinal epidemiology of children who have survived an showed that children with a wide range of causes of ARF have ARF episode irrespective of cause. We found that children a significant risk for chronic renal injury, ESRD, and with ARF who survived hospitalization have a high risk of mortality irrespective of ARF cause. death, as only 139/174 (79.9%) were alive 3–5 years after the In light of the high incidence of chronic renal injury after initial incident. When combining those who died during ARF that we observed, we suggest that children should be initial hospitalization and those who died subsequently, the screened regularly for signs of renal disease after an ARF survival rate is 139/245 (56.8%), and thus a high proportion episode. Of the 17/29 (59%) children who had signs of renal (106/245 (43.2%)) of children who sustain ARF are deceased injury, only 6/17 (35%) had follow-up with a pediatric 3–5 years following initial incident. nephrologist. Four of these children, two with chronic renal Estimates for renal survival are limited as we only queried insufficiency and two with hypertension, have conditions that the Texas Children’s hospital ESRD databases, and patients require prompt interventions to optimize growth and prevent who may have progressed to ESRD at other programs were further end-organ injury. Although the others had signs of not included in our analysis. Although only a small renal injury that would not need immediate attention, long- proportion of patients had primary renal conditions as the term follow-up to intervene early is vital, as injury cause of ARF, this group had the lowest renal survival (24/35 progression is likely to occur. Furthermore, adult studies (68.6%)). At 3–5 years after the initial ARF episode, only (5/ have found that even minor renal disease is an independent 139 (3.6%)) survivors without primary renal conditions predictor of and mortality,17–19 and progress to ESRD. therapeutic interventions can slow progression and reverse To evaluate renal injury, we used four concrete measures renal injuries.20 Early intervention for the pediatric patient (microalbuminuria, hyperfiltration or decreased GFR, hema- with minor renal dysfunction may provide a significant turia, and hypertension) as markers of renal injury Although impact on long-term cardiovascular health. only 29/125 potential subjects were evaluated for renal injury, Unfortunately, the retrospective design of this study did the addition of 32 patients who died after hospitalization and not allow further analysis into the causes of deaths, the 16 who progressed to ESRD represents 77/173 (44.5%) of all impact of primary and comorbid illness on mortality, nor hospital survivors. We found that 17/29 (59%) of patients assess the impact that ARF per se had on outcome in these had at least one abnormality at follow-up visit. We included children who were already at risk for death. Clearly, hyperfiltration (chronic kidney disease stage 1) because prospective trials will be needed to answer these questions, experimental studies have incriminated glomerular hyperfil- further define the pathophysiologic mechanisms of disease, tration in mediating progressive renal damage from various and search for therapeutic interventions to limit renal injury initiating injuries.15 However, the Schwartz formula for and improve outcomes. hyperfiltration can overestimate GFR in small children and is not the most sensitive way to evaluate hyperfiltration in older Conclusions children. Nonetheless, only four patients had hyperfiltration After an ARF episode, children have a high incidence of death as the sole marker of renal injury. and long-term renal injury. As the risk for long-term renal As noted in Table 4, children who have hyperfiltration are injury is high, children should be evaluated periodically for more likely to have microalbuminuria and only two patients signs of renal injury for years after the initial insult. who had normal renal function were found to have Prospective longitudinal multi-center studies are needed to microalbuminuria. Microalbuminuria is considered a marker further define this population, define the etiology of of vascular endothelium dysfunction. In adults, urinary sustained renal injury, and evaluate strategies to slow or albumin/creatinine ratios as low as 6.7 mg/g have been prevent progressive renal injury in the wake of ARF. associated with all-cause morality in subjects who otherwise 16 appeared healthy. We were unable to perform first-morning MATERIALS AND METHODS urine collections due to research design; so we cannot Epidemiology discount that some patients may have had orthostatic This cross-sectional cohort study analyzes the 3–5-year survival proteinuria. Despite this limitation, only one patient had outcomes of the 174 children with ARF who survived hospitalization solely microalbuminuria as a sign of renal injury. Whether at Texas Children’s Hospital between January 1998 and June 2001. microalbuminuria is a reliable marker for renal injury by Patients were selected if they had a diagnosis of ARF on either the itself in this population is yet to be determined. discharge or death summary. Patients were then screened for estimated corrected GFR and only those patients with a GFR Although this study encompasses a small proportion of all p75 ml/min/1.73 m2 were selected for further analysis. The decision survivors in a single center, we found a high rate of residual to start RRT was made by the renal physician on call. or ongoing renal injury in those with primary renal/urologic Children with chronic renal disease or previous transplant kidney diseases, as well as those with other causes of renal injury, prior to the ARF episode were excluded from the study. The such as ischemia and nephrotoxic injury. Institutional Review Board of Baylor College of Medicine approved Previous studies have shown that specific ARF causes, such this human study.

Kidney International (2006) 69, 184–189 187 original article DJ Askenazi et al.: Follow-up of children after ARF

Physicians from the Texas Children’s Hospital Renal, Cardiology, analysis was performed for two categories of nonparametric Hepatology and Bone Marrow Transplant sections were provided a variables. Mann–Whitney U-test was performed on nonparametric list of survivors from the original cohort in their field to assess measurements that had multiple categories. Fisher’s exact test was survival. In addition, the medical records departments at Texas used when evaluating nonparametric renal injury difference out- Children’s Hospital and the Texas Department of Health’s Vital comes when the number of subjects in any group was less than 5. Statistics office were queried. To assess renal survival, we queried the Analysis of PedsQLTM subscale, total score means, and standard Texas Children’s Hospital dialysis and transplantation database. deviation was carried out using analysis of variance. Po0.05 was Subgroup analysis was performed to compare for those with primary considered statistically significant. renal/urologic disease vs others, those who initially required RRT vs none, and those who were admitted to ICU vs non-ICU patients. ACKNOWLEDGMENTS This work was supported by a research fellowship from the National Assessment of renal injury Kidney Foundation and the Texas Affiliate of the National Kidney Foundation. The families of patients who had not progressed to ESRD were initially contacted to participate by mail, and those who did not respond were contacted by telephone. Of the 126 potential REFERENCES 1. Shaw NJ, Brocklebank JT, Dickinson DF et al. Long-term outcome for participants in the study, 29 agreed to participate in the study children with acute renal failure following cardiac surgery. Int J Cardiol (Figure 1). After obtaining informed consent, subjects had physio- 1991; 31: 161–165. logical measurements performed during a single study visit, including 2. Scharer K, Krmar R, Querfeld U et al. Clinical outcome of height and weight with associated percentiles; history and physical Schonlein–Henoch purpura in children. Pediatr Nephrol 1999; 13: 816–823. examination was performed. We estimated GFR by Schwartz estimate 3. Abitbol CL, Bauer CR, Montane B et al. Long-term follow-up of extremely for creatinine clearance (CCl) and compared this to normative data low birth weight infants with neonatal renal failure. Pediatr Nephrol 2003; (normal CCl ¼ 90–150 ml/min/1.73 m2).21 Chronic renal failure was 18: 887–893. 2 4. Krmar RT, Ferraris JR, Ramirez JA et al. Ambulatory blood pressure defined as CClo90 ml/min/1.73 m ; hyperfiltration was defined as 2 monitoring after recovery from hemolytic uremic syndrome. Pediatr CCl4150 ml/min/1.73 m . Serum creatinine was performed with Nephrol 2001; 16: 812–816. Vitros E-950TM (Ortho/Clinical Diagnostics; Rochester, NY). 5. Bar J, Kaplan B, Wittenberg C et al. Microalbuminuria after pregnancy A clean-catch urine specimen was collected from the subjects. complicated by pre-eclampsia. Nephrol Dial Transplant 1999; 14: Due to experimental design, a first morning void was not performed 1129–1132. 6. Morgera S, Kraft AK, Siebert G et al. Long-term outcomes in acute renal for most children. Urine albumin/creatinine ratio was calculated failure patients treated with continuous renal replacement therapies. Am s using the Bayer DCA 2000 analyzer (Elkhart, IN). Measurement of J Kidney Dis 2002; 40: 275–279. microalbuminuria by this method is a valid surrogate for 24-h 7. Counahan R, Cameron JS, Ogg CS et al. Presentation, management, microalbumin collection as spot urine albumin/creatinine ratio complications, and outcome of acute renal failure in childhood: five years’ 22 experience. Br Med J 1977; 1: 599–602. correlates well with 24-h collection for albumin. Microalbuminur- 8. Weiss RA, Spitzer A. Renal failure in childhood. Compr Ther 1983; 9: ia greater than 30 mg/24 h is construed as a reliable marker for renal 31–40. injury;22–24 thus, spot urine albumin/creatinine ratio X30 was 9. Williams DM, Sreedhar SS, Mickell JJ et al. Acute : a pediatric experience over 20 years. Arch Pediatr Adolesc Med 2002; 156: 893–900. defined as microalbuminuria. Evaluation of urine albumin/creati- 10. Andreoli SP. Acute renal failure. Curr Opin Pediatr 2002; 14: 183–188. nine ratio showed that healthy children have between 7 and 12% 11. Stewart CL, Barnett R. Acute renal failure in infants, children and adults. chance to have ratios above 30 on random samples and a 2.6% Crit Care Clin 1997; 13: 575–590. chance on first-morning urine collections.25–27 Hematuria was 12. Mendley SR, Langman CB. Acute renal failure in the pediatric patient. Adv s Ren Replace Ther 1997; 4: 93–101. analyzed with Multistix 10SG reagent strips for urinalysis (Bayer 13. Filler G. Acute renal failure in children: aetiology and management. 2161; Strawberry Hill, UK). Paediatr Drugs 2001; 3: 783–792. Assessment of systolic blood pressure and diastolic blood 14. Hui-Stickle S, Brewer ED, Goldstein SL. Pediatric ARF epidemiology at a pressure was determined by taking the mean of three relaxed, tertiary care center from 1999 to 2001. Am J Kidney Dis 2005; 45: 96–101. 15. Brenner BM, Lawler EV, Mackenzie HS. The hyperfiltration theory: a seated, upper extremity readings with a blood pressure monitor s paradigm shift in nephrology. Kidney Int 1996; 49: 1774–1777. (Dinamap ) and cuff of an appropriate size. A subject was 16. Romundstad S, Holmen J, Kvenild K et al. Microalbuminuria and all-cause considered hypertensive if his/her systolic blood pressure or diastolic mortality in 2089 apparently healthy individuals: a 4.4-year follow-up blood pressure was greater than the 95th percentile for sex, height, study. The Nord–Trondelag Health Study (HUNT), Norway. Am J Kidney Dis 2003; 42: 466–473. and age as described by the Fourth Report on High Blood Pressure 17. Henry RM, Kostense PJ, Bos G et al. Mild renal insufficiency is associated 28 in Children and Adolescents. Children on antihypertensive with increased cardiovascular mortality: The Hoorn Study. Kidney Int 2002; medications were considered hypertensive in our study only if they 62: 1402–1407. received medications for blood pressure control, and not for 18. Ix JH, Shlipak MG, Liu HH et al. Association between renal insufficiency and inducible ischemia in patients with coronary artery disease: the heart proteinuria, afterload reduction, tachycardia, or other abnormalities. and soul study. J Am Soc Nephrol 2003; 14: 3233–3238. In order to assess health-related quality of life, we administered 19. Manjunath G, Tighiouart H, Coresh J et al. Level of kidney function as a the PedsQLTM 4.0 Generic Scale questionnaire during their clinic visit risk factor for cardiovascular outcomes in the elderly. Kidney Int 2003; 63: in either English or Spanish, depending on primary language. Data 1121–1129. TM 29–31 20. Brenner BM, Zagrobelny J. Clinical renoprotection trials involving were compared to normative PedsQL standards. Internal angiotensin II-receptor antagonists and angiotensin-converting-enzyme consistency reliability was explored for all age groups. inhibitors. Kidney Int Suppl 2003 (Suppl 85): S77–S85. 21. Schwartz GJ, Haycock GB, Edelmann Jr CM et al. A simple estimate of Statistical analysis glomerular filtration rate in children derived from body length and 2 plasma creatinine. Pediatrics 1976; 58: 259–263. w analysis was used to determine renal and patient survival 22. Nathan DM, Rosenbaum C, Protasowicki VD. Single-void urine samples differences. Demographics of potential participants were analyzed can be used to estimate quantitative microalbuminuria. Care using Student’s t-test when parametric variables were used. w2 1987; 10: 414–418.

188 Kidney International (2006) 69, 184–189 DJ Askenazi et al.: Follow-up of children after ARF original article

23. Hiar C. Performance of the DCA 2000 Microalbumin/Creatinine System. 28. National high blood pressure education program working group on high Bayer: Tarrytown, NY, 1997, pp 1–14. blood pressure in children and adolescents. The forth report on the 24. Meigs JB, D’Agostino Sr RB, Nathan DM et al. Longitudinal association of diagnosis, evaluation, and treatment of high blood pressure in children glycemia and microalbuminuria: the Framingham Offspring Study. and adolescents. Pediatrics 2004; 114: 555–576. Diabetes Care 2002; 25: 977–983. 29. Varni JW, Seid M, Kurtin PS. PedsQL 4.0: reliability and validity of 25. Hoy WE, Mathews JD, McCredie DA et al. The multidimensional nature of the Pediatric Quality of Life Inventory version 4.0 generic core renal disease: rates and associations of albuminuria in an Australian scales in healthy and patient populations. Med Care 2001; 39: Aboriginal community. Kidney Int 1998; 54: 1296–1304. 800–812. 26. Mueller PW, Caudill SP. Urinary albumin excretion in children: factors 30. Varni JW, Seid M, Knight TS et al. The PedsQL 4.0 Generic Core Scales: related to elevated excretion in the population. Ren Fail sensitivity, responsiveness, and impact on clinical decision-making. 1999; 21: 293–302. J Behav Med 2002; 25: 175–193. 27. Pugia MJ, Lott JA, Kajima J et al. Screening school children for 31. Varni JW, Burwinkle TM, Seid M et al. The PedsQL 4.0 as a pediatric albuminuria, proteinuria and occult blood with dipsticks. Clin Chem Lab population health measure: feasibility, reliability, and validity. Ambul Med 1999; 37: 149–157. Pediatr 2003; 3: 329–341.

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