Is a Complete Urological Evaluation Necessary in All Newborns With

International Journal of Urology (2007) doi: 10.1111/j.1442-2042.2007.01764.x

Original Article

Is a complete urological evaluation necessary in all newborns with asymptomatic renal ectopia? Francesco Arena,1 Salvatore Arena,1 Antonina Paolata,2 Alfredo Campenni,3 Biagio Zuccarello1 and Giuseppe Romeo1 Units of 1Pediatric Surgery and 2Neonatology, Department of Medical and Surgical Pediatric Sciences, and 3Unit of Nuclear Medicine, Department of Radiological Sciences, University of Messina, Messina, Italy

Aim: To evaluate if a complete urological screening is justified by potential urological anomalies in newborns or infants with asymptomatic renal ectopia (RE). Methods: The database records of 60 consecutive neonatal cases of RE diagnosed at the authors’ hospital from 1990 to 2004 were retrospectively reviewed. Results: At diagnosis, mean patient age was 1.6 months. In 58 of 60 patients, the suspected diagnosis of RE was made during prenatal or postnatal screening ultrasonography, including two newborns with anorectal malformation. There were 24 patients with crossed RE (C-RE) and 36 patients with simple RE (S-RE). A solitary RE was present in two patients. The most frequent associated urological abnormality was vesico- ureteral reflux (37.5% of C-RE and 16.6% of S-RE). Hydronephrosis was detected in seven RE and five contralateral kidneys. An obstructive megaureter was present in one patient with C-RE. In 40% of S-RE and 92.9% of C-RE, the 99mTc DMSA documented reduction of function of RE. The longitudinal diameter of the ectopic kidney was significantly smaller than the contralateral one. Other non-renal diseases were present in 15% of patients, of which the most frequent was cryptorchidism (6.6%). Conclusions: A complete urological evaluation is necessary in newborns with C-RE for the high incidence of associated urological anomalies, of which VUR is the most frequent. A complete urological evaluation is also reasonable in patients with S-RE who have a pelvic dilatation. No diagnosis or treatment of the associated urological diseases, in consideration of congenital decreased function of the ectopic kidney, might predispose these children to improvement of renal function impairment.

Key words: hydronephrosis, renal ectopia, vesico-ureteral reﬂux.

Introduction The aim of this study was to evaluate if a complete urological screening is justified by potential urological associated anomalies in Renal ectopia (RE) describes a kidney that lies outside the renal fossa. newborns or infants with asymptomatic ectopic kidney. Simple RE (S-RE) refers to kidney that remains in the ipsilateral retroperitoneal space. The most common position is in the pelvis opposite the sacrum and below the aortic bifurcation. By definition, crossed RE (C-RE) exists when a kidney is located on the opposite side of the Methods midline from where the ureter enters the bladder. Ninety percent of C-RE kidneys are fused from below to the normally located kidney. From 1990 in our hospital a facultative screening program has offered Renal ectopia has been reported in approximately 1 in 1000 autop- hip and kidney ultrasound (US) to all newborns in their first 4 months sies.1 Crossed ectopic kidney is a rare anomaly, with an estimated of life. From 1990 to 2004, 32 221 newborns were screened at our incidence of 1 in 7500 autopsies or 1 in 14 000 pediatric admissions.2–4 institution and a RE was diagnosed in 60 patients (0.2%), consisting of Some screening studies have reported the incidence of RE to be 1 in 39 boys (65%) and 21 girls (35%). Horseshoe kidneys were not con- 5000 patients.1,5 Most cases of RE remain asymptomatic and the considered in this study. At diagnosis, patient age ranged from newborn to dition is incidentally discovered during screening for associated 4 months (mean 1.6 months). 99m congenital anomalies or during imaging for other purposes.6 The final diagnosis in each patient was confirmed by static tech- In previous studies, a high incidence of associated urological abnor- netium dimercapto-succinic acid (DMSA) scan. In two patients a mag- malities was reported in children with RE.7 Hydronephrosis is the most netic resonance urography (MRU) was necessary, and in another two common significant finding in RE,1 and the presence of associated patients an intravenous urography (IVU) was performed. Voiding cys- vesico-ureteral reflux (VUR) is estimated in 25–70% of cases.4,7–9 For tourethrography (VCUG) was performed on all male patients and a these reasons, prenatal or incidental diagnosis of RE is considered an color-Doppler cystosonography with echocontrast (CystoUS) was per- absolute indicator for an early and complete investigation of the urinary formed on all female patients. VUR was graded according to the 10 tract, even in asymptomatic children. International Reflux Committee guidelines. We used the Society for Fetal Urology classification system to grade dilatation of the upper urinary tract.11 Differential renal function was calculated by DMSA Correspondence: Francesco Arena MD, Unit of Pediatric Surgery, Department scan. In the right and left kidneys, DMSA uptake was measured 2 h of Medical and Surgical Pediatric Sciences, University of Messina, Poli- after intravenous injection of radioisotope, as previously reported.12 For clinico, Viale Gazzi, Messina 98125, Italy. Email: [email protected] the ectopic kidney, attenuation correction was achieved using the Received 5 June 2006; accepted 19 January 2007. geometric mean of the anterior and posterior view.

Fig. 2 Case of right crossed renal ectopia (C-RE) in a patient with anorectal malformation and recto-bulbar fistula. (a) Voiding cystouretrography showing a right grade III vesico-ureteral reflux in C-RE. A recto-bulbar fistula is evident (arrow). (b) Renal scan (DMSA) showing a right fused C-RE. Right kidney is small with decreased concentration.

Statistical analysis

Comparisons of demographic and clinical parameters among groups were performed using the chi-squared test and unpaired t-test. Statis- tical signiﬁcance was considered achieved if P < 0.05. Data are expressed as mean Ϯ SEM.

Results

An S-RE was found in 36 patients (60%), and a C-RE was found in 24 patients (40%). S-RE was pelvic in 33 patients (91.6%) and lumbar in three patients (8.4%). The S-RE was left side in 14 patients (39%), right side in 18 (50%) and bilateral in two (5.5%). A solitary ectopic kidney was present in two patients (5.5%). In C-RE, ectopic kidneys were crossed and fused in 18 of 24 patients (75%), while they were crossed but not fused in six (25%). In all crossed but non-fused kidneys, the ectopic kidney was in the pelvic position. The C-RE was left side in 18 patients (75%) and right side in six (25%). In 58 of 60 patients, the suspected diagnosis of RE was performed during prenatal (23 patients, 38.3%) or postnatal screening US (35 patients, 58.3%). Two newborns were affected by anorectal malformation, so diagnosis of RE was carried out during preoperative genito- urinary US. In 30% of patients, a renal agenesis was initially suspected. Fig. 1 Case of a right crossed renal ectopia (C-RE). (a) Voiding cystouret- Associated non-renal diseases existed in nine patients (15%). Of the rography showing a bilateral grade III vesico-ureteral reﬂux. Left kidney is patients with S-RE, three had cryptorchidism (8.3%) and one had enlarged and malrotated. (b) Renal scan (DMSA) showing L-shaped C-RE, absent vagina (2.8%). Of patients with C-RE, two had imperforate anus proves a good concentration of an ectopic kidney. Left kidney is lengthened with sacral agenesis (8.3%), one had bowel malrotation (4.2%) and one and renal concentration is inhomogeneous. had hypospadias with cryptorchidism (4.2%).

Fig. 3 Case of left crossed renal ectopia (C-RE) in a patient with bowel malrotation. (a) Magnetic resonance urography showing a left C-RE with hydroure- theronephrosis and weak renal parenchyma. The right kidney appears rotated along the vertical axis and fused in middle line with the contralateral kidney. The small bowel is left localized. (b) Renal ecocolor Doppler demonstrating two renal adherent parenchymas in the right renal fossa. (c) Renal scan (DMSA) showing a unique renal formation (fused kidneys) in right paramedian site.

Associated urological abnormalities were recorded in 24 patients (eight girls and three boys). A VUR grade II–III was found in nine with RE (40%). In particular, these were present in 15 of 24 patients patients (37.5%) with C-RE (three bilateral and six unilateral, five (62.5%) with C-RE (eight fused and seven non-fused kidneys) and in fused and four non-fused) (Figs 1, 2) and in six (16.6%) with S-RE (one nine of 26 patients (25%) with S-RE (all in pelvic position). bilateral and five unilateral, all in pelvic position). Of patients with A VUR was documented in 15 patients with RE (25%). VUR was unilateral RE, VUR involved the orthotopic kidney in 80%. A signifi- bilateral in four patients (three girls and one boy) and unilateral in 11 cantly greater incidence of VUR was recorded in girls than in boys (11

a b c d

Fig. 4 Flow diagram of infants with (a,b) simple renal ectopia (S-RE) and (c,d) crossed renal ectopia (C-RE) with a renal pelvic dilatation of (a,c) <10 mm or (b,d) Ն10 mm. CystoUS, cystoultrasonography with echocontrast; DMSA, 99mTc dimercapto-succinic acid scan; DTPA, 99mTc diethylenetriamine pentaacetic acid; IVU, intravenous urography; MRU, magnetic resonance urography; nUS, neonatal ultrasonography; pUS, prenatal ultrasonography; UPJ, uretero-pelvic junction; US, ultrasonography; UVJ, uretero-vesical junction; VCUG, voiding cystouretrography; VUR, vesico-ureteral reﬂux.

girls and four boys, respectively, P < 0.005). The grade of VUR was 49.5 Ϯ 7.0 mm; P < 0.0001). In C-RE, ultrasonographic measurement significantly greater in girls than in boys (P < 0.05). No significant of longitudinal diameter was possible in 12 of 24 patients. The longi- difference in the incidence of VUR was recorded between right or left tudinal diameter of the ectopic kidney was also significantly smaller side of RE. At 2 years, a spontaneous recovery of VUR was observed in than the contralateral one in C-RE (mean 25.0 Ϯ 10.0 mm vs three of four boys (75%) and in six of 11 girls (54.5%), four with S-RE 43.0 Ϯ 4.7 mm; P < 0.005). and two with C-RE. One boy (25%) and five girls (45.4%) required operative treatment, performed at a mean age of 38 Ϯ 8 months. Tran- Discussion strigonal reimplantation was performed in a boy with grade III bilateral VUR, and four girls underwent endoscopic treatment. Diagnosis of RE is usually achieved using DMSA scan, because A renal pelvic dilatation was detected on prenatal or neonatal ultra- DMSA remains bound to the cortical renal proximal tubules and is sound in seven RE non-refluxing units (grade III in two patients and minimally excreted. In terms of using antero-posterior, latero-lateral grade II in five patients) and in five orthotopic kidneys (grade III in and oblique projections, DMSA has been shown to be useful for diag- two patients and grade II in three patients). These patients underwent nosing RE below L-2 and renal cortical lesions, and uptake measure- further investigations (DTPA with furosemide test in all patients, IVU ments provide a marker for the functioning cortical mass.13 in two patients and MRU in two patients) that documented ureteropel- The primary goal of our study was to evaluate the incidence of vic junction obstruction (UPJO) affecting the ectopic kidney in one- associated urological abnormalities in the randomized population of patient with C-RE (non-fused kidneys) and the contralateral orthotopic newborns with RE, selected after findings of RE during prenatal or kidney in two patients (one patient with S-RE and one patient with postnatal screening US. A high incidence of associated urological C-RE, non-fused). According to Anderson-Hynes, patients affected by abnormalities has been reported in patients with RE.1,4,7 The increased UPJO underwent a pyeloplasty when they were 23 Ϯ 4.6 months incidence of VUR in patients with RE was initially reported by Kramer (range 18–27 months). A uretero-vesical junction obstruction (ectopic and Kelalis,9 who studied a small group of symptomatic patients. In ureter) was recorded in one patient with C-RE. In this patient, the their study VCUG indicated an incidence of 52% and 70% in C-RE and ectopic kidney was poorly functioning, while the contralateral ortho- S-RE, respectively. Hendren et al.3 observed reflux in six of nine chil- topic kidney was malrotated, with fetal appearance (Fig. 3). This dren and Kheradpir et al.4 in three of five children with C-RE. Our data, patient required transtrigonal reimplantation with tailoring of the according to Guarino et al.,7,8 show that the risk of VUR, even if ectopic megaureter when he was 6 months old. significant, was lower than what has been previously reported and it In 40% of the patients with unilateral S-RE, DMSA scan docu- differs according to the type of RE. In our study, patients with C-RE mented decreased function of the ectopic kidney (mean 37.5 Ϯ 5.6%; had a risk of VUR of 37.5%, without any significant difference between range 29–47%). In C-RE, measurement of differential renal function fused and non-fused kidneys, while those with S-RE had an incidence using DMSA scan was possible in 14 patients; however, the superim- of just 16.6%. It was suggestive that all S-RE affected by VUR had a position of the fused kidney prevented the differential evaluation of pelvic RE. Of our patients with unilateral RE, the VUR affected the renal function in remaining C-RE. In 13 patients (92.9%) with unilat- orthotopic kidney in 80%. We found that girls with RE have a higher eral C-RE, DMSA scan documented decreased function of the ectopic incidence and grade of reflux. Our data suggest that ectopic kidneys are kidney (mean 33.2 Ϯ 3.8%; range 28–38%). more disease-prone than are normal kidneys: they are often hypoplastic The longitudinal diameter of the ectopic kidney was significantly or dysplastic.4 On this basis, we encourage a VCUG in boys and a smaller than the contralateral one in S-RE (mean 37.4 Ϯ 4.7 mm vs CystoUS in girls affected by C-RE, for the high risk of associated VUR

4 © 2007 The Japanese Urological Association Hidden morbidity in renal ectopia and the evidence that postnatal US is a poor predictor of VUR.14 In our the condition is not recognized and treated. In patients with S-RE, a opinion, a cystographic evaluation is necessary in S-RE with a neonatal complete urological evaluation is warranted if a renal pelvic dilatation pelvic dilatation Ն8 mm. coexists. In our patients the ectopic kidneys were significantly smaller than the contralateral, orthotopic ones, in particular in C-RE. Also, C-RE kidneys were significantly smaller than S-RE ones. In a previous study, References Guarino et al. documented that in a high percentage of children with RE, the ectopic kidney had a primitive reduction of function.7 Also in 1 Gleason PE, Kelalis PP, Husmann DA, Kramer SA. Hydronephrosis in renal ectopia: Incidence, etiology and significance. J. Urol. 1994; 151: our experience DMSA scan documented a reduction of differential 1660–1. renal function of the ectopic kidney in 40% of patients with S-RE and 2 Malek RS, Kelalis PP, Burke EC. Ectopic kidney in children and in 90% of patients with C-RE. frequency of association with other malformations. Mayo Clin. Proc. Previous reports documented a high incidence of hydronephrosis in 1971; 46: 461–7. children with RE.1,2 Gleason et al.1 noted an incidence of hydroneph- 3 Hendren WH, Donahoe PK, Pfeister RC. Crossed renal ectopia in rosis of 56% in ectopic kidneys and 26% in non-ectopic contralateral children. J. Urol. 1976; 7: 135–44. kidneys. Dilatation of the ectopic renal pelvis was the result of UPJO in 4 Kheradpir MH, Bodaghi E. Crossed renal ectopia in children. Pediatr. 37% of patients and ureterovesical junction obstruction in 15%. Surg. Int. 1992; 7: 69–72. Kramer and Kelalis9 reported a 33% incidence of hydronephrosis for 5 Sheih CP, Liu MB, Hung CS, Yang KH, Chen WY, Lin CY. Renal UPJO in children with RE. In our study, in accordance to Guarino abnormalities in school children. Pediatrics 1989; 84: 1086–8. 6 Conway DA, Meza MP, Docimo SG. Pelvic hydronephrotic kidney et al.,7 the incidence of hydronephrosis is lower because we just masquerading as obstructed bowel. Urology 2003; 61: 1033–4. enrolled asymptomatic newborns. In fact, in our experience, only three 7 Guarino N, Tadini B, Camardi P, Silvestro L, Lace R, Bianchi M. The (5%) children required surgery because affected by UPJO. incidence of associated urological abnormalities in children with renal It is clear that an abnormal position of the kidney can lead to poor ectopia. J. Urol. 2004; 172: 1757–9. outflow with subsequent predisposition to hydronephrosis, calculi and 8 Guarino N, Sacco Casamassima MG, Tadini B, Marras E, Lace R, infection. This condition occurs late and it explains the higher Bianchi M. Natural history of vesicoureteral reflux associated with incidence of hydronephrosis in older patients.1 kidney anomalies. Urology 2005; 65: 1208–11. On the evidence of high incidence of urological anomalies, in par- 9 Kramer SA, Kelalis PP. Ureteropelvic junction obstruction in children ticular in patients affected by C-RE, we propose different evaluation on with renal ectopy. J. Urol. (Paris) 1984; 90: 331–3. the basis of renal pelvic dilatation (Fig. 4). 10 Lebowitz RL, Olbing H, Parkkulainem KV, Smellie JM, Tamminem-Mobius TE. International reflux study in children: Associated abnormalities of spinal growth have been found in 50% International system of radiographic grading of vesico-ureteric reflux. and genital anomalies in 40% of patients with RE.15 In our series just Pediatr. Radiol. 1985; 15: 105–7. two patients with C-RE and imperforate anus with recto-urethral fistula 11 Ritchie E, Reisman EM, Zaontz MR, Hatch DA, Wacksman J, Maizels showed an agenesia of the sacrum and skeletal anomaly. The incidence M. Grading nephroureteral dilatation detected in the first year of life: of genital abnormalities in RE was 10.3% in boys (three patients with Correlation with obstruction. J. Urol. 1992; 148: 609–11. cryptorchidism and one with cryptorchidism and hypospadias) and 12 Kawamura J, Hosokawa S, Yoshida O. Validity of 99mTc 2.9% in girls (one patient with absent vagina). However, our data are dimercaptosuccinic acid renal uptake for an assessment of individual influenced by the age of the studied patients. Many malformations of kidney function. J. Urol. 1978; 119: 305–10. female genitalia are detected late with the occurrence of gynecologic 13 Gordon I. Paediatric aspects of radionuclides in nephrourology. In: symptoms (pelvic pain, infertility, repeated abortion). Murray IPC, Ell PJ (eds). Nuclear Medicine in Clinical Diagnosis and Treatment, Vol. I, 2nd edn. Churchill Livingstone, London, 1998; In conclusion, in prenatal or neonatal diagnosis of C-RE, a complete 277–90. urological evaluation is always necessary because a high proportion of 14 McIlroy PJ, Abbott GB, Anderson NG, Turner JG, Mogridge N, Wells these patients have associated urological anomalies, of which VUR is JE. Outcome of primary vesico-ureteric reflux detected following fetal the most common. The presence of VUR in the contralateral, normally pelvic dilatation. J. Paediatr. Child Health 2000; 36: 569–73. positioned kidney, together with decreased function of the ectopic 15 Miles BJ, Moon MR, Belville WD, Kiesling VJ. Solitary crossed renal kidney, might predispose these children to renal function impairment if ectopia. J. Urol. 1985; 133: 1022–3.