The etiology of renal scars in infants with pyelonephritis and vesicoureteral reflux

We aimed to investigate, by means of dimercaptosuccinic acid (DMSA) scan, the relations between vesicoureteral reflux (VUR) and its degree, pyelonephritis during infancy, and renal parenchymal findings. Seventy-four infants with pyelonephritis, 44 girls and 30 boys (mean age at their first pyelonephritic episode 4.12 months, median 3 months), were enrolled in the study. Voiding cystourethrography (VCU) and ultrasonography (US) were performed within 6 weeks following the infection. DMSA was performed at least 4 months after the urinary tract infection (UTI). The renal parenchymal pathology was defined as focal or multifocal defects or as a split renal uptake of less than 45%. DMSA scintigraphy revealed that 19% (14/74) of the children had renal damage. Renal parenchymal findings were observed only when VUR was present, and its grade was above 3/5. No abnormality was found in 51 renal units without reflux, 9 with VUR grade 1/5, and 54 with grade 2/5. Renal pathology was observed in 9/24 renal units with VUR grade 3, 3/8 with grade 4, and 2/2 with grade 5. No correlation was found between renal parenchymal defects and clinical presentation of the pyelonephritis, type of the microorganism, presence of bacteremia, or the number of recurrent infections. In adequately treated infants, renal damage is probably due to a reflux-associated, preexisting, congenital renal parenchymal pathology and not to the inflammatory process. We suggest that DMSA scintigraphy should not be performed routinely in every infant with UTI and should be reserved primarily for children with VUR grade 3 and above. Received: 17 February 1999 / Revised: 30 June 1999 / Accepted: 7 July 1999     

Post-pyelonephritic renal scars are not associated with vesicoureteral reflux in children

PURPOSE: Children with pyelonephritis are at risk for renal damage. We assess the value of clinical signs and urological abnormalities in predicting renal scars in children following pyelonephritis. MATERIALS AND METHODS: A total of 64 hospitalized children (29 females and 35 males, median age 2.9 years) underwent ultrasonography and technetium labeled dimercapto-succinic acid (DMSA) scintigraphy imaging within 1 week following the diagnosis of the first pyelonephritis. Voiding cystourethrography was performed 8 weeks after the diagnosis. Followup DMSA scintigraphy was performed in 58 patients after 2 years of followup. RESULTS: Urological abnormalities observed were vesicoureteral reflux (VUR, grade 2 or higher) in 11 patients (19%), nonrefluxing and nonobstructed megaureter in 2 (4%) and pyeloureteral obstruction in 1 (2%). The first DMSA scintigraphy showed parenchymal defects in 48% of patients. VUR did not increase the risk of renal defects. At 2 years after the infection 12 of the 58 patients (21%) had renal scars. Nine of these patients did not have VUR. However, 2 patients with high grade VUR and repeat infections demonstrated deterioration of kidney function during followup. The patients with renal scars were older than those without scars (3.1 vs 0.8 years, p = 0.0291) at the time of infection. CONCLUSIONS: Renal scars after first pyelonephritis are in most cases not associated with abnormalities of the urinary tract, but are caused by the infection itself. However, structural abnormalities may predispose to recurrent infections. Following pyelonephritis new renal scars may develop in all age groups in both sexes.     

Primary vesicoureteral reflux mediated renal scarring after urinary tract infection in Thai children

AIM: To evaluate the association between primary vesicoureteral reflux (VUR) and renal scarring in children using 99 m Technetium-labelled dimercaptosuccinic acid (DMSA). METHODS: Children attending at Songklanagarind Hospital from 1987 to 2002 were evaluated. RESULTS: Ages at diagnosis of VUR in 46 boys and 52 girls were 1.1+/-1.6 and 2.9+/-2.5 years, median 0.6 and 2.3 years, respectively (P<0.001). DMSA scans were performed at 4.1+/-3.6 years. Renal parenchymal damage was detected in 34 kidneys (22%) of 154 demonstrated refluxing ureters, and one kidney (2%) of 42 non-refluxing ureters (P=0.002). Of 79 refluxing ureters in boys and 75 refluxing ureters in girls, there were 25 and nine renal scars, respectively (32% and 12%, P=0.003). Renal scars in VUR grades I-V were 11%, 7%, 12%, 44% and 64%, respectively (P<0.001). Multivariate analysis revealed that high grade VUR (P<0.001), age of diagnosis of VUR greater than 5 years (P=0.001), and male gender (P=0.002) were the most significant risk factors for renal scarring. CONCLUSION: High-grade VUR, age of diagnosis of VUR greater than 5 years and male gender were the most significant risk factors for renal scarring.     

The Efficacy of Tc99m Dimercaptosuccinic Acid (Tc-DMSA) Scintigraphy and Ultrasonography in Detecting Renal Scars in Children with Primary Vesicoureteral Reflux (VUR)

Introduction: Pyelonephritis-induced renal scarring in children is a major predisposing factor for proteinuria, hypertension, and ultimate renal failure. The aim of this study was to investigate and compare the efficacy of Tc99m dimercaptosuccinic acid (Tc-DMSA) renal scintigraphy and renal ultrasonography (USG) in detecting renal scars in children with primary vesicoureteral reflux (VUR). Materials and methods: Tc-DMSA scan and USG studies were done in 62 children who were admitted to our clinic between 1997 and 2003 because of documented urinary tract infection (UTI) and diagnosed with primary VUR. Renal scarring detection rates of Tc-DMSA scan and USG were compared according to reflux grades. Results: In the whole group, renal scars were detected by Tc-DMSA scan and USG in 55% and 38% of refluxing units, respectively. Detection rates of Tc-DMSA and USG according to reflux grades were as follows: 47% and 29 % in low-grade VUR (grades 1 and 2), 46 % and 25% in mid-grade VUR (grade 3), 76% and 65% in high-grade VUR (grades 4 and 5), respectively. Conclusion: USG was found to be an inappropriate study in the detection of renal parenchymal scars, irrespective of the reflux grade. In this study, Tc-DMSA scan detected scars in 35% of kidneys reported to be normal on USG.     

Vesicoureteral reflux increases the risk of renal scars: a study of unilateral reflux

The aim of this study was to assess the impact of vesicoureteral reflux (VUR) on renal scar following acute pyelonephritis by comparing the refluxing renal units with nonrefluxing renal units in children with unilateral primary VUR. Forty-eight children with unilateral primary VUR diagnosed after the first pyelonephritis were enrolled. Mean age of patients was 1.0±1.6 years (29 boys and 19 girls). All patients underwent renal ultrasonography and renal 99 m-technetium dimercaptosuccinic acid (DMSA) scan within three days following the diagnosis of pyelonephritis, and voiding cystourethrography (VCU) was performed soon after fever subsided and the infection was controlled. The DMSA scan was rechecked six months after the initial study when the first scan showed a renal defect. The first DMSA showed renal defects in 34 (70.8%) out of 48 of the refluxing renal units and in 13 (27.1%) out of 48 of the nonrefluxing renal units (P<0.01, OR: 6.54). At six months after the infection, 23 (47.9%) out of 48 refluxing renal units and seven (14.6%) out of 48 nonrefluxing renal units had renal scars on DMSA scan (P<0.01, OR: 5.39). The prevalence of renal scars did not vary significantly according to the grade of VUR. The CRP level on admission was significantly higher in patients with acute renal defect and scar. In conclusion, VUR increases the risk of post-pyelonephritic renal scars in children.     

Distribution of renal parenchymal damage on 99m-Tc DMSA scintigraphy in vesico-ureteric reflux

During a 2 year period renal scintigraphy was performed in 64 children prior to surgery for vesico-ureteric reflux (VUR). In total 126 kidneys were examined. Renal scintigraphy was performed 3 hours after intravenous injection of 99m-technetium labelled dimercaptosuccinic acid (DMSA). The renal parenchyma was assessed as normal in 64 kidneys and abnormal in 62. Renal parenchymal damage was revealed in the upper pole in 42 cases, the middle lateral part in 27, the lower pole in 47 and the middle medial part in 25. The whole kidney was affected in 21 cases. Damage within one or two poles was present in 59 of the 62 kidneys with parenchymal damage. Renal scintigraphy is regarded a sensitive technique for detection of renal parenchymal damage. The DMSA scintigraphy can reveal even minor scars. It can be recommended as a routine investigation in evaluating children with VUR.     

Long-term follow-up of children with surgically treated vesicorenal reflux: renal growth

Renal growth after successful surgical correction of vesicoureterorenal reflux (VUR) in childhood was observed in 137 female and 22 male patients over a mean follow-up period of 10.5 years. The renal parenchymal area was determined using a compensatory planimeter. For each measured value, the standard deviation score (SDS) was calculated by comparison with a normal population. On average, renal growth after reflux operation nearly paralleled the expected normal growth rate. Scarred kidneys had a worse growth prognosis than refluxing renal units (RU) without renal damage, growth retardation being correlated with the degree of pyelonephritic changes. The diminished growth rate of scarred kidneys was accompanied by a compensatory growth of the contralateral kidney. In the absence of renal scars, a modest tendency toward growth retardation was seen in kidneys with previously high degrees of VUR. In 39.7% of the unscarred RU with an initial SDS less than -0.5, accelerated growth (change in SDS of 0.5 or more) was observed. Accelerated growth was most accentuated on small unscarred kidneys (initial SDS less than -2.0).     

Evaluation of renal scarring in children with primary VUR by 99mTc-DMSA renoscintigraphy

Renal scarring in 271 kidneys of 172 children with primary vesicoureteral reflux (VUR) was evaluated by 99mTc-DMSA renoscintigraphy. 58% of refluxing kidneys were with renal scar by the initial DMSA renoscintigraphy. Only 52% of these kidneys showed good correlation between the findings on IVP and DMSA renoscintigram. Of the 144 refluxing kidneys with normal IVP, 41% had renal scarring on DMSA renoscintigram. DMSA renoscintigram revealed widespread renal scarring in 28% of kidneys with only calyceal clubbing and in 60% of those with segmental cortical thinning on IVP. It is realized that IVP was an in-sensitive method to evaluate renal scarring of refluxing kidneys and such kidneys with segmental renal scar on IVP accompanies more widespread scar on DMSA renoscintigram. These cases were allocated to 2 age groups, younger than 3 years and older than 4 years. In the former group less than 10% of kidneys with low grade VUR and about 40% with high grade UVR had widespread renal scarring. On the contrary, in the latter group severe renal scar was recognized in more than 20% of kidneys with low grade VUR and in about 60% with high grade UVR.     

Management of vesicoureteral reflux in children

Background. Vesicoureteral reflux (VUR) in children has been reported in many studies. However, the management of VUR is still controversial. Methods. One hundred and fourteen children with primary VUR were divided into two treatment groups: medical (group A) and surgical (group B). The clinical courses and X-ray films of cystography and intravenous pyelography of these children were reviewed retrospectively, using the International Reflux Study Committee Classification. Results. In children less than 1 year of age, VUR was observed more frequently in boys. However, this ratio was reversed in children aged 2 years or more. Sixty-three percent of all refluxing ureters had reflux of grade III or higher at the initial examination. Spontaneous cessation of VUR was observed in 17% of group A ureters, and all had grade III or less reflux. Renal parenchymal scars were already present at the initial examination in 23% of kidneys with refluxing ureters. Recurrent urinary tract infections became less frequent after anti-reflux surgery. The progression of renal scars and renal growth retardation was observed more frequently in group B children. Conclusions. From these observations, it appeared that surgical management of VUR did not prevent the progression of renal scarring or renal growth retardation. Early detection of and intervention in VUR may prevent the progression of renal scarring and renal growth retardation. However, a multicenter, prospective, randomized controlled study would be necessary to confirm these findings. Received: October 4, 1999 / Accepted: January 15, 2000     

Nonrefluxing colonic conduits: a long-term life-table analysis

We evaluated 25 patients undergoing urinary diversion with a nonrefluxing colonic conduit. Renal scarring developed in 10% of the kidneys during a median followup of 12.7 years. In 11 renal units (22%) deterioration of the ureteroenteric anastomosis occurred due to the development of reflux or stricture. Of these kidneys 45% had scarring; no renal unit in which the anastomosis remained intact had renal scars (p less than 0.001). Of our patients 96% had bacterial colonization of the colonic conduit but this was not associated with renal scarring if the urinary diversion was anatomically intact.     

Early renal parenchymal histological changes in an experimental model of vesico-ureteral reflux and the role of apoptosis

OBJECTIVES: To observe early renal parenchymal cellular changes in an experimental model of vesico-ureteral reflux (VUR) and to show whether the apoptotic pathway plays a role in these cellular changes. MATERIAL AND METHODS: Fourteen New Zealand breed rabbits were used and were divided into two equal groups (control and experimental groups). Urine samples were obtained in a sterile manner and cultured. In the study group, reflux was created in the right kidneys surgically. Renal scintigraphy and voiding cystourethrography (VCUG) were performed in both groups on Day 17. The kidneys were examined in terms of histology, apoptotic activity and caspase activity. RESULTS: No growth was observed in urine cultures in either group. VUR was manifested in only two rabbits in the experimental group on VCUG. On renal scintigraphy, no renal scarring was observed in either of the groups and renal uptake values were in the normal range. There was a greater increase in collagen in the right kidneys in the experimental group than in the control group and apoptotic activity was significantly increased in the study group: 0% in the control group, 10.8%+/-0.7% in the experimental group (p<0.001). Caspase-6 activity was strongly positive and caspase-8 and -9 activities were moderately positive in the right kidneys of the experimental group. Caspase-6 activity was moderately positive, and caspase-8 and -9 activities were weakly positive in the contralateral kidneys of the experimental group. Caspase activities in the control group were negative (p<0.001). CONCLUSIONS: In this experimental model of VUR, apoptotic activity was initiated via the caspase-8 and -9 pathway and collagen tissue increased in the renal parenchyma where reflux occurred. The balance of apoptotic activity may play a key role in the occurrence of reflux nephropathy.     

Vesico-ureteric reflux in the damaged non-scarred kidney

Renal damage without scarring is a rare manifestation of reflux nephropathy, and is infrequently reported in the literature. A retrospective review of a large series of patients with urinary tract disorders at the hospital for Sick Children, Great Ormond Street, identified 12 patients with vesico-ureteric reflux (VUR) with no evidence of scarring but with renal damage as assessed using technetium 99m dimercaptosuccinic acid (^99mTc-DMSA) scan. There were 9 simplex kidneys, the differential function was between 33% and 43% (mean 38%). On follow-up to date (mean 6.7 years) all kidneys show stable differential function with neither improvement nor deterioration. Only 8 children had a urinary tract infection. Renal damage without evidence of a focal scar associated with VUR may be a manifestation of growth arrest possible due to glomerular damage. The sensitivity of^99mTc-DMSA may reveal the permanent nature of the renal damage.     

Split renal function does not change after successful treatment in children with primary vesico-ureteric reflux

OBJECTIVE: To evaluate the renal growth pattern in patients with primary vesico-ureteric reflux (VUR) using long-term measurements of split renal function with 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy. PATIENTS AND METHODS: In all, 712 children aged < 16 years (466 boys and 246 girls) with primary VUR were referred to our hospital from July 1991 to December 2000. VUR was diagnosed by voiding cysto-urethrography. The patients were treated either surgically (group 1) or conservatively (group 2) and followed with serial 99mTc-DMSA scintigraphy for up to 10 years. There were 942 examinations in 367 of 712 patients who had repeat scintigraphy. Patients with secondary VUR, VUR to a solitary or fused kidney, or upper urinary tract obstruction, were excluded. Five of 298 patients (1.7%) who had ureteric reimplantation had a febrile urinary tract infection (UTI) soon after surgery but none recurred (recurrence is an indication for surgery in children with VUR); there was no febrile UTI in the 69 patients in group 2. Planar scintigraphy with 99mTc-DMSA was used to assess the absolute uptake (AU) of each kidney, measured as a percentage of the injected dose, and the relative uptake (RU = AU of each kidney/AU of both kidneys) calculated. The initial examination was at least 4 weeks after any febrile UTI in most patients. Serial studies were conducted 1 year after surgery and then biannually in group 1. In group 2 the DMSA scan was repeated every 2-3 years. The change in split renal function was compared with the RU of the right kidney. RESULTS: The RU of the right kidney at the initial scan correlated closely with those on repeated scans in both groups. The correlation coefficients were 0.99 in group 1 and 0.94-0.97 in group 2 at every study. The change of RU remained within 0.05 in all patients after treatment. CONCLUSIONS: Under strict control of UTI, split renal function in children with primary VUR does not change. There may be no possibility of accelerated or compensatory growth of the kidney with reflux nephropathy, but no concern about deterioration and atrophy either.     

ACE I/D gene polymorphism predicts renal damage in congenital uropathies

We investigated angiotensin converting enzyme gene (ACE I/D) polymorphism as a risk for progressive renal damage in congenital uropathies. The ACE I/D genotype was determined in 196 Caucasian patients with congenital uropathies and 163 individuals with no clinical or sonographic evidence of any urological malformations. The study group included patients with ureteropelvic junction obstruction (n=49), primary obstructive megaureter (n=19), primary vesicoureteral reflux (VUR) (n=67), and posterior urethral valves (n=27). Thirty-four patients were excluded because of additional diseases or insufficient follow-up. There was no difference in the ACE I/D distribution between children with uropathies and normal controls (II 16%, ID 56%, DD 28% vs. II 26%, ID 50%, DD 24%). Renal lesions were found in 99 of 162 children by ultrasonography, intravenous pyelography, and nuclear scans. In these children there was significant over-representation of the DD genotype (II 11%, ID 53%, DD 36%) compared with normals (P<0.005, X²=14.9) or with patients with uropathies but no renal lesions (II 23%, ID 62%, DD 15%, P<0.005, X²=14.9). Because ACE I/D has been linked with progressive deterioration of renal function, we evaluated a subset of patients with initially normal kidneys who developed radiographic renal lesions (n=28). Among these patients there was an even greater over-representation of the DD genotype (II 0%, ID 43%, DD 57%, P<0.001, X²=22.6) compared with patients with uropathies but no radiographic lesions. Multivariate analysis revealed that the DD genotype is a risk factor for parenchymal destruction, which was independent of time of diagnosis, surgical intervention, or urinary tract infection. This finding was particularly relevant in patients with VUR who constituted the majority with initially normal kidneys who developed radiographic damage (22/28). Indeed, the odds ratio of developing parenchymal damage with VUR was significantly increased if the individual had the DD genotype (4.2, 95% confidence interval 1.4–13.0). In conclusion the ACE I/D gene polymorphism is a risk factor for renal parenchymal damage in patients with congenital urological abnormalities and appears particularly relevant in children with VUR, where it is an independent predisposing factor. Received: 3 November 1998 / Revised: 3 March 1999 / Accepted: 3 March 1999     

Vesicoureteral reflux in male and female neonates as detected by voiding ultrasonography

BACKGROUND: Vesicoureteral reflux (VUR) is assumed to be congenital, and its early diagnosis is desired in order to prevent acquired renal damage. However, the incidence of VUR in neonates remains to be revealed. METHODS: Two thousand newborn babies (1048 boys and 952 girls) underwent voiding ultrasonography (an ultrasound examination of urinary tract during provoked voiding). Those who showed transient renal pelvic dilation during voiding, who had small kidneys, or who subsequently developed urinary infection underwent voiding cystourethrography. RESULTS: Transient renal pelvic dilation was observed in 16 babies (0.8%), including one boy with small kidneys. Among the rest of the babies, one boy had a small kidney, and nine babies subsequently developed urinary infection. Voiding cystourethrography revealed VUR in 24 ureters of 16 children (11 boys and 5 girls). Dimercaptosuccinate renoscintigraphy confirmed small kidneys, with generally reduced tracer uptake in a total of three boys, all having VUR. Voiding ultrasonography detected transient renal pelvic dilation in 17 (71%) of the 24 kidneys with VUR and, strikingly, 16 of the 17 (94%) kidneys with high-grade VUR (grade III or more). CONCLUSION: This study effectively detected VUR in 0.8% of the neonates (mostly of high grades and predominantly in males) and voiding ultrasonography showed a decided usefulness for the detection of VUR. The male preponderance of VUR in neonates was considered to be due to the occurrence of congenitally small kidneys, with reflux found exclusively in males and easier ultrasound detection of VUR in male neonates because the majority of diagnoses are reported to be high grades of VUR.     

Evaluation of renal function in children with primary VUR up to two years old

The function of 99 refluxing kidneys of 61 children up to two years old at the time of diagnosis was evaluated by 99mTc-DMSA renoscintigraphy, urinary beta 2-microglobulin (beta 2-MG), alpha 1-microglobulin (alpha 1-MG) and N-acetyl-beta-D-glucosamidase (NAG). High grade reflex (grade IV, V) was found in 45% of the cases. 76%, 51% and 92% of the cases showed abnormally high value of urinary beta 2-MG, alpha 1-MG and NAG, respectively. These results indicate that they have already had tubular dysfunction at the time of diagnosis. DMSA renoscintigraphy of 82 refluxing kidneys of 49 children was performed. Of these, 48% had renal scar and 28% had serious renal dysfunction [DMSA uptake rate less than 18%]. 10-20% of low grade VUR had less than 18% DMSA uptake rate. Two patterns were noticed in the group in which urinary beta 2-MG ranged 0.33-1.0. One was characterized by good bilateral renal function with slight tubular damage and the other serious renal dysfunction with fixed tubular damage. No remarkable recovery of the renal function was noticed after antireflux operation in the second pattern cases. In many cases, in which urinary beta 2-MG was more than 1.0, improvement of DMSA uptake rate was noticed after antireflux operation.     

Primary vesicoureteric reflux as a predictor of renal damage in children hospitalized with urinary tract infection: a systematic review and meta-analysis

Renal parenchymal disease after urinary tract infection (UTI) has been associated with the development of hypertension and renal functional impairment. A systematic literature review and meta-analysis was performed to determine how effectively the finding of primary vesicoureteric reflux (VUR) on micturating cystography (MCU) in children hospitalized with UTI predicted renal parenchymal disease on (99m)Technetium-dimercaptosuccinic acid ((99m)Tc-DMSA) scintigraphy. Medline, Embase, and PubMed were use to find reports with original data for children hospitalized with bacteriologically-proven UTI who had undergone both MCU and (99m)Tc-DMSA scintigraphy, and which also reported both positive and negative results of these tests. A meta-analysis of likelihood ratios positive and negative for MCU was then performed, including tests for heterogeneity. Twelve valid studies were found, seven with data for 537 children, with a positive (99m)Tc-DMSA scan prevalence of 59% overall, and seven studies with data for 1062 kidneys, with a positive (99m)Tc-DMSA scan prevalence of 36%. The likelihood ratio positive for MCU was 1.96 (95% CI, 1.51 to 2.54) for children, and 2.34 (1.53 to 3.57) for kidneys. The likelihood ratio negative was 0.71 (0.58 to 0.85) for children and 0.72 (0.61 to 0.86) for kidneys. There was evidence of heterogeneity. The meta-analysis showed that a positive MCU increases the risk of renal damage in hospitalized UTI patients by about 20%, whereas a negative MCU increases the chance of no renal involvement by just 8%. VUR is hence a weak predictor of renal damage in pediatric patients hospitalized with UTI. Physicians should be aware of the limitations of using MCU-detected primary VUR as an effective screening test for renal damage in this population. Furthermore, the pathogenesis of renal damage in such patients is probably complex because it is often detected without demonstrable VUR.     

ACE gene polymorphism and renal scarring in primary vesicoureteric reflux

The objective of this study was to investigate whether mutations of the renin-angiotensin system genes are involved in primary vesicoureteric reflux (VUR) and VUR-associated renal scarring. The M235T polymorphism of the angiotensinogen ( ATG) gene, the I/D polymorphism of the angiotensin converting enzyme ( ACE) gene, and the A1166C polymorphism of the angiotensin II type 1 receptor ( AT1) gene were identified in 77 patients with primary VUR (aged 6.9+/-3.2 years, mean+/-SD) and 80 healthy controls (aged 33+/-7 years). Thirty-eight of the 77 VUR patients had low-grade VUR (grade I-III) and 39 had high-grade VUR (grade IV and V). Renal scarring was found in 43 VUR patients, while 34 patients had normal kidneys on dimercaptosuccinic acid scan. The ACE gene polymorphism was determined by polymerase chain reaction and the ATG and AT1 gene polymorphisms were determined by single-step LightCycler technology. We found significant over-representation of the DD genotype in patients with renal scarring (44 %) compared with normal controls (23%, P<0.05) and patients with no scar formation (21%, P<0.05). Significantly higher D and significantly lower I allele frequencies were present in VUR patients with scarred kidneys (D allele 0.64 and I allele 0.36) compared with controls (D allele 0.53 and I allele 0.47, P<0.05) and patients with unscarred kidneys (D allele 0.4 and I allele 0.6, P<0.05). No differences in the ATG and AT1 genotype distributions and allele frequencies were observed in VUR patients compared with the normal population. The DD genotype and D allele of ACE may be a genetic susceptibility factor contributing to scar formation in VUR. We detected no linkage of genetic polymorphisms of ATG and AT1 to VUR and VUR-associated renal scarring.     

Vesicoureteral reflux and complete ureteral duplication. Conservative or surgical management?

PURPOSE: The management of vesicoureteral reflux (VUR) in a duplicated collecting system (DS) is controversial. Available literature is sparse and it does not assess all co-factors. We compared the outcome of VUR in DS cases with VUR in single system (SS) cases, given similar clinical management in the 2 groups. MATERIALS AND METHODS: A retrospective cohort study was done to compare the outcome of VUR in 35 children (44 units) with a DS and in 95 (150 units) with an SS. Patients with secondary reflux, incomplete duplication and ureterocele were excluded. Two groups were similar in terms of prognostic factors. Mean followup in the DS and SS groups was 43 and 48 months, respectively. Outcomes of interest were spontaneous resolution or uncomplicated persistence vs surgical correction. The same criteria were used to intervene surgically in the 2 groups. RESULTS: In the DS group 24 of 35 patients (69%) underwent surgery compared with 25 of 95 (25%) in the SS group. Multivariate analysis showed an association between surgery due to complications and the presence of DS (p = 0.0001). Higher grade and female gender were independent predictors (p = 0.02 and 0.0007, respectively). The likelihood of undergoing surgery was the same for low grade VUR (I and II) in the DS and SS groups (p = 0.16). No resolution was seen in the duplex group with severe VUR at a mean followup of 42 months. CONCLUSIONS: Low grade VUR in DS cases has an outcome similar to that of VUR in SS cases. Females with moderate or high grade VUR and a DS should be treated differently because they present more often with complications.     

Clinical course of 735 children and adolescents with primary vesicoureteral reflux

The purpose of this retrospective cohort study was to report the clinical course of children with primary vesicoureteral reflux (VUR). Between 1970 and 2004, 735 patients were diagnosed with VUR and were systematically followed in a single tertiary renal unit. Patients were followed up for a mean time of 76 months (6 months to 411 months). The events of interest were reflux resolution, renal damage, urinary tract infection (UTI), chronic kidney disease (CKD), and hypertension. Survival analysis was performed in order to evaluate reflux resolution and CKD. Renal damage was detected at admission in 319 patients (43.4%). Continuous low-dose antibiotic prophylaxis was administered to 624 patients (91.2%); 499 (73%) patients subsequently had no UTI or fewer than three episodes. The median time of persistence of reflux according to Kaplan–Meier analysis was 38 months for grade I/II [95% confidence interval (95% CI), 33–43], 98 months for grade III (95% CI, 78.5–105), and 156 months for grade IV/V (95% CI, 122–189). Twenty patients (3%) developed hypertension. It was estimated that the probability of CKD was 5% at 10 years after diagnosis of VUR; for children diagnosed after 1990 the probability of CKD was only 2%. Renal function impairment occurred in patients with severe bilateral reflux or in patients with contralateral renal hypoplasia. There has been an improvement of prognosis for patients diagnosed in the past 15 years.