Dextranomer/hyaluronic acid endoscopic injection is effective in the treatment of intermediate and high grade vesicoureteral reflux in patients with complete duplex systems.

PURPOSE: Endoscopic subureteral injection of dextranomer/hyaluronic acid has become an established alternative to long-term antibiotic prophylaxis or surgical treatment for vesicoureteral reflux. We evaluated the effectiveness of endoscopic injection of dextranomer/hyaluronic acid in intermediate and high grade vesicoureteral reflux in patients with complete duplex collecting systems. MATERIALS AND METHODS: A total of 123 children underwent endoscopic correction of intermediate or high grade vesicoureteral reflux using injection of dextranomer/hyaluronic acid into complete duplex systems between 2001 and 2010. Vesicoureteral reflux was diagnosed by voiding cystourethrogram, and dimercapto-succinic acid scan was performed to evaluate the presence of renal scarring. Followup ultrasound and voiding cystourethrogram were performed 3 months after the outpatient procedure and renal ultrasound thereafter every 2 years. Mean followup was 6.7 years. RESULTS: Complete duplex systems were unilateral in 110 patients and bilateral in 13. Reflux severity in the 136 refluxing units was grade II in 1 (0.7%), III in 52 (38.2%), IV in 61 (44.9%) and V in 22 (16.2%). Dimercapto-succinic acid scan revealed renal functional abnormalities in 63 children (51.2%). Vesicoureteral reflux resolved after the first endoscopic injection of dextranomer/hyaluronic acid in 93 ureters (68.4%), after a second injection in 35 (25.7%) and after a third injection in 8 (5.9%). Febrile urinary tract infection developed in 5 patients (4.1%) during followup. No patient required ureteral reimplantation or experienced significant complications. CONCLUSIONS: Our results confirm the safety and efficacy of endoscopic injection of dextranomer/hyaluronic acid in eradicating intermediate and high grade vesicoureteral reflux in patients with complete duplex systems. We recommend this minimally invasive, 15-minute outpatient procedure as a viable option for treating intermediate and high grade vesicoureteral reflux in patients with complete duplex collecting systems.

Incidence of febrile urinary tract infections in children after successful endoscopic treatment of vesicoureteral reflux: a long-term follow-up.

OBJECTIVE: To evaluate the incidence of febrile urinary tract infection (UTI) after successful endoscopic correction of intermediate and high-grade vesicoureteral reflux (VUR). STUDY DESIGN: Medical records of 1271 consecutive children (male, 411; female, 903) who underwent successful endoscopic correction of VUR were reviewed. Factors potentially influencing postoperative UTIs, such as history of presentation, age, sex, grade of VUR, renal scarring, and agent used for the endoscopic injection, were analyzed. RESULTS: Febrile UTI developed in 73 children (5.7%) after successful endoscopic correction of VUR. Thirty-nine children had a single episode of UTI, and 34 children had two or more episodes at 1 month to 5.9 years (median, 1 year) after correction of VUR. With multivariate analysis, female sex (P < .001), history of preoperative bladder/bowel dysfunction (BBD; P = .005), and BBD after endoscopic correction (P = .001) were revealed to be the most important independent risk factors for a febrile UTI after successful correction of VUR. CONCLUSIONS: The incidence of febrile UTIs after successful correction of intermediate and high grade VUR is low. Female sex and BBD were the most important risk factors in the development of febrile UTI. Our data supports the importance of assessing bladder and bowel habits in older children with febrile UTIs after endoscopic correction of VUR.

Prevalence of duplex collecting systems in familial vesicoureteral reflux.

PURPOSE: Duplication of the ureter and renal pelvis is the most common upper urinary tract anomaly in childhood with a reported incidence of 0.8%. Familial nature of vesicoureteral reflux (VUR) is well recognized with a prevalence of 27-51% in siblings of children with VUR and 66% rate of VUR in offsprings of parents with previously diagnosed VUR. Although VUR is known to be the most common abnormality associated with renal duplex systems, the prevalence and significance of renal duplication in familial VUR is not known. The aim of this study was to determine the prevalence and significance of duplex collecting systems in familial VUR. METHODS: Between 1998 and 2009, the parents of 237 index patients with grade III-V VUR were asked permission to screen siblings younger than 6 years old for VUR. A total of 513 children in 237 families were identified to have VUR (237 index patients, 276 siblings). Families were divided into three groups: Group I, families with only boys affected Group II, families with only girls affected and Group III, families with boys and girls affected. RESULTS: In 39 families (16.5%) only boys had VUR (Group I), in 89 families (37.5%) only girls had VUR (Group II) and in 109 families (46%) boys and girls were affected (Group III). Duplex collecting systems were present in 39 (7.6%) patients. The prevalence of duplex systems was significantly higher in Group I (15%) compared to Group II (6%) and Group III (6.4%), (p < 0.01). Duplex systems were present in 15% of boys in Group I and only in 4% of boys in Group III (p < 0.01). Patients with duplex systems had a significantly higher grade of VUR than patients without duplex systems (p < 0.01). CONCLUSION: Families with exclusively boys affected with VUR have a higher rate of prevalence of duplex collecting systems. This has implications for genetic counseling and for modeling the inheritance of VUR.

Endoscopic treatment of primary grade V vesicoureteral reflux using hyaluronic acid copolymer (DX/HA).

PURPOSE: Since DX/HA was approved by the Food and Drug Administration in 2001 as an acceptable tissue-augmenting substance for subureteral injection, endoscopic treatment has become increasingly popular for treating vesicoureteral reflux (VUR). However, most paediatric urologists still continue to recommend ureteral reimplantation as the treatment of choice in the management of grade V VUR. The purpose of this study was to prospectively evaluate the effectiveness of endoscopic subureteral injection of DX/HA in the treatment of grade V reflux. MATERIALS AND METHODS: During 2001-2009, 56 children (35 males, 21 females) with primary grade V VUR underwent endoscopic treatment using DX/HA. Their ages ranged from 4 months to 11 years. Forty-nine patients had unilateral grade V VUR, and seven had bilateral grade V (63 refluxing ureters including 17 duplex systems). Renal scarring on dimercaptosuccinic acid was observed in 39 kidneys (mild scarring 13, moderate scarring 14 and severe scarring 12). In all patients, endoscopic injection was made after inserting the needle within the wide ureteral orifice. Renal ultrasound and voiding cystourethrogram was performed 3 months after the endoscopic treatment. If VUR had not resolved, the patient was considered for further endoscopic treatment. After the VUR was resolved, children were followed with renal ultrasound at 1 year and every 2 years thereafter. RESULTS: The VUR completely resolved after first injection of DX/HA in 33 (52.4%) ureters and downgraded to grade I VUR in 7 (11.1%) ureters. 19 (30.2%) ureters required a second injection, and 4 (6.3%) ureters required a third injection to resolve VUR. No children in this series needed reimplantation of ureters or presented with ureteral obstruction during follow-up. CONCLUSION: Endoscopic treatment with DX/HA is effective in eradicating grade V primary reflux. This simple and minimally invasive treatment should be offered to all parents of children with grade V VUR as an alternative to ureteral reimplantation.

Renal parenchymal damage in intermediate and high grade infantile vesicoureteral reflux.

PURPOSE: The association of vesicoureteral reflux, urinary tract infection and renal scarring is well recognized. We evaluated the incidence of renal parenchymal scarring in a large series of infants with primary high grade vesicoureteral reflux. MATERIALS AND METHODS: The medical records of 549 consecutive infants with primary high grade vesicoureteral reflux between 1985 and 2006 were reviewed. A total of 473 infants (86.1%) presented with febrile urinary tract infections, 63 (11.5%) were screened for sibling vesicoureteral reflux and 13 (2.4%) were investigated because of prenatally diagnosed hydronephrosis. Age at diagnosis was defined as patient age at the first voiding cystourethrogram. Renal parenchymal scarring was evaluated by dimercapto-succinic acid scan and classified into 3 groups, including mild--focal defects with between 40% and 45% relative uptake of renal radionuclide, moderate--relative uptake between 20% and 40%, and severe--a shrunken kidney with relative uptake less than 20%. RESULTS: Of the 549 infants 292 (53%) were boys and 257 (47%) were girls with a median age of 6 months (range 2 to 12). Reflux was unilateral in 160 and bilateral in 389 (938 ureters). Reflux grade was II to V in 19, 372, 458 and 89 ureters, respectively. All patients with grade II reflux had high grade reflux on the contralateral side. Renal parenchymal scarring was present in 122 of the 458 infants (27%) evaluated with dimercapto-succinic scan. The incidence of renal parenchymal scarring was only 9% in infants without a history of urinary tract infection and 29% in those who presented with a urinary tract infection (p <0.01). Moderate to severe renal parenchymal scarring was present in 55 infants, of whom 73% were male and 27% were female. CONCLUSIONS: The data show that moderate to severe renal scarring is associated with grade IV and V reflux, and male sex. The incidence of renal scarring is significantly lower in infants in whom high grade vesicoureteral reflux is detected by screening before the development of urinary tract infection. Early detection may prevent urinary tract infection related renal parenchymal scarring.

Endoscopic treatment of moderate and high grade vesicoureteral reflux in infants using dextranomer/hyaluronic acid.

PURPOSE: Renal parenchymal injury in vesicoureteral reflux occurs early, in most patients before age 3 years. It is generally believed that early prevention of urinary tract infections may decrease the amount of renal parenchymal damage. Endoscopic treatment for vesicoureteral reflux has become an established alternative to long-term antibiotic prophylaxis and ureteral reimplantation. We prospectively evaluated the effectiveness and safety of dextranomer/hyaluronic acid copolymer for high grade vesicoureteral reflux in infants. MATERIALS AND METHODS: A total of 276 infants, including 124 boys and 152 girls, with a median age of 7 months (range 2 to 12) underwent endoscopic treatment for vesicoureteral reflux with dextranomer/hyaluronic acid. Reflux was detected in 225 infants following investigation for urinary tract infection, in 46 following screening for sibling vesicoureteral reflux and in 5 for prenatally diagnosed hydronephrosis. Vesicoureteral reflux was unilateral in 85 infants and bilateral in 191 (467 refluxing ureters). Reflux was grade II in 14 ureters, grade III in 188, grade IV in 248 and grade V in 17. Dimercapto-succinic acid scan was performed in 250 infants and it demonstrated renal scarring in 43 (17.2%). RESULTS: Vesicoureteral reflux completely resolved in 373 ureters (79.9%) after a single injection of dextranomer/hyaluronic acid and it was downgraded to grade I in 21 (4.4%). Of the ureters 65 (14%) required a second injection and 8 (1.7%) required a third injection to resolve reflux. All patients underwent endoscopic treatment on an outpatient basis. There were no complications except in 1 patient, who was readmitted to the hospital the next day with acute pyelonephritis. Three children had urinary tract infections during followup, of whom 1 was found to have recurrent reflux on investigation. CONCLUSIONS: Endoscopic treatment with dextranomer/hyaluronic acid is safe and highly effective for eradicating high grade vesicoureteral reflux in infants. Early intervention in infants with high grade reflux may change its natural history and protect against renal scarring.

New contralateral vesicoureteral reflux after endoscopic correction of unilateral reflux--is routine contralateral injection indicated at initial treatment?

PURPOSE: As more and more pediatric urologists use endoscopic therapy as a primary treatment option for vesicoureteral reflux, newer indications for this procedure are being considered. Recently it was suggested that contralateral nonrefluxing ureters should be treated prophylactically in patients undergoing unilateral endoscopic correction of vesicoureteral reflux. We analyzed the incidence of newly diagnosed contralateral reflux after endoscopic correction of unilateral reflux and identified possible risk factors for its development. MATERIALS AND METHODS: Between 1996 and 2004, 662 patients underwent endoscopic correction of unilateral grades II to V vesicoureteral reflux. Of the ureters 97% had grades III to V reflux. The tissue augmenting substance used for endoscopic treatment was polytetrafluoroethylene from 1996 to 2000 and dextranomer/hyaluronic acid from 2001 to 2004. There were 203 males (30.7%) and 459 females (69.3%) with an age at endoscopic treatment of 2 months to 11 years. Voiding cystourethrograms performed 3 months after endoscopic treatment of unilateral vesicoureteral reflux were analyzed in all patients to document newly diagnosed contralateral reflux. RESULTS: A total of 67 children (10.1%), including 18 boys and 49 girls, showed new contralateral reflux on voiding cystourethrogram after endoscopic correction of unilateral reflux. Contralateral VUR was grades I to IV in 16 (23.9%), 17 (25.4%), 27 (40.3%) and 7 patients (10.5%), respectively. There was no correlation between the severity of ipsilateral reflux and the development of contralateral reflux. Patient age and gender did not influence the development of new contralateral reflux. CONCLUSIONS: The low incidence and lower grade of newly diagnosed contralateral vesicoureteral reflux after endoscopic correction of unilateral reflux does not support prophylactic treatment of nonrefluxing contralateral ureters.

Endoscopic treatment of vesicoureteral reflux associated with ureterocele.

PURPOSE: We determined the value of endoscopic treatment for vesicoureteral reflux associated with ureterocele. MATERIALS AND METHODS: From 1984 to 2005, 109 children with a median age of 6 months underwent endoscopic ureterocele puncture. Ureterocele presented as a part of a duplex system in 97 of patients (89%) and as part of a single system in 12 (11%). Vesicoureteral reflux was seen to the lower ipsilateral moiety in 53 patients and in 32 contralateral kidneys (85 refluxing renal units). Puncture was performed with a 3Fr Bugbee electrode. High grade vesicoureteral reflux or breakthrough infection while on antibiotic prophylaxis served as the indication for the surgical correction of vesicoureteral reflux. Median followup after endoscopic correction was 10 years (range 1 to 21). RESULTS: Spontaneous vesicoureteral reflux resolution following successful ureterocele puncture was seen in 36 of the 85 refluxing renal units (42%) and in 5 (6%) reflux was downgraded. The latter patients were withdrawn from antibiotic prophylaxis and they did well. A total of 33 refluxing renal units with vesicoureteral reflux into the lower moiety of the ureterocele kidney and 11 contralateral refluxing renal units underwent endoscopic correction. Reflux was corrected in 31 of the 44 refluxing renal units (70%) after a single injection and it resolved after a second injection in another 9 (21%). In 4 refluxing renal units (9%) endoscopic correction failed and open reimplantation was done. Of the 109 patients (13%) 14 had vesicoureteral reflux to the ureterocele moiety following endoscopic puncture. Of those patients endoscopic correction resolved reflux in 3, reflux resolved spontaneously in 5 and upper pole partial nephrectomy was performed in 4 due to a nonfunctioning moiety. The remaining 2 patients did well without antibiotic prophylaxis. CONCLUSIONS: Our data show that endoscopic treatment of vesicoureteral reflux associated with ureterocele is a simple, long-term effective and safe procedure, avoiding the need for open surgery in the majority of patients following endoscopic puncture of ureterocele.

Endoscopic treatment for high grade vesicoureteral reflux in infants.

PURPOSE: Minimally invasive endoscopic treatment for vesicoureteral reflux has become an established alternative to long-term antibiotic prophylaxis and surgical intervention in children. We determined the long-term efficacy and safety of this treatment for high grade reflux in infants. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 411 consecutive infants who underwent endoscopic treatment of grade III to V vesicoureteral reflux between June 1985 and October 2004. A total of 29 patients (7%) were excluded from study because they were lost to followup or the medical records were incomplete. Of the remaining 382 infants, including 203 males, 274 had bilateral and 108 had unilateral vesicoureteral reflux. This represented 642 high grade refluxing units with grade III to V disease in 232, 339 and 71, respectively. A dimercapto-succinic acid scan performed in 312 infants revealed renal scarring in 88 (28%). The tissue augmenting substance used for endoscopic injection was polytetrafluoroethylene and dextranomer/hyaluronic acid copolymer in 432 and 210 ureters, respectively. Endoscopic treatment was done at a median age of 7 months (range 2 months to 1 year). Median followup in these patients was 7 years (range 6 months to 20 years). RESULTS: Complete resolution of vesicoureteral reflux after a single injection occurred in 443 ureters (69%), including 73% with dextranomer/hyaluronic acid copolymer and 65% with polytetrafluoroethylene. Of the 642 ureters 127 (20%) required more than 1 injection to correct vesicoureteral reflux. In 60 ureters vesicoureteral reflux was downgraded to grade I or II and no further treatment was given, while 12 ureters that failed to respond to endoscopic treatment required open surgical intervention. Only 1 ureter required reimplantation to treat vesicoureteral obstruction. CONCLUSIONS: Endoscopic correction is a safe, effective, minimally invasive outpatient procedure for high grade vesicoureteral reflux in infants. Early correction of vesicoureteral reflux may provide protection from reflux associated renal damage and prolonged antibiotic use.

Familial vesicoureteral reflux: influence of sex on prevalence and expression.

PURPOSE: Familial clustering of vesicoureteral reflux implies that genetic factors have an important role in the pathogenesis of vesicoureteral reflux. We investigated the impact of sex on familial vesicoureteral reflux. MATERIALS AND METHODS: Between 1998 and 2003 we identified 159 white families with at least 2 children (range 2 to 5) with vesicoureteral reflux confirmed by a voiding cystourethrogram. Families were divided into 3 groups, including group 1 with only boys affected (29 or 18%), group 2 with only girls affected (57 or 36%) and group 3 with boys and girls affected (73 or 46%). Clinical characteristics, reflux grade and associated renal anomalies in these 3 groups were compared using the Mann-Whitney U and chi-square tests for statistical analysis. RESULTS: Sisters of index female patients were at significantly higher risk for vesicoureteral reflux than brothers (p <0.01). Boys in group 1 had a significantly higher grade of vesicoureteral reflux than boys in group 3, and girls in groups 3 and 2 (p = 0.018, <0.001 and <0.0001, respectively). Severe renal scarring was present in 7% of boys in group 1, 6.6% of boys in group 3, 1.3% of girls in group 3 and 1.9% of girls in group 2. Duplex kidneys were present in 15.3% of boys in group 1 but only in 2.3% of boys in group 3 (p <0.01), 5.7% of girls in group 3 and 5.8% of girls in group 2. Age at diagnosis was not significantly different among boys in groups 1 and 3, and girls in group 2 (median 0.9, 0.6 and 1.9 years, respectively). CONCLUSIONS: The risk and severity of vesicoureteral reflux in siblings depends on the sex of the affected child. Brothers of index male patients have higher grade of reflux and higher rate of associated duplex systems. This has implications for genetic counseling and for modeling the inheritance of vesicoureteral reflux.

Subureteral dextranomer/hyaluronic acid injection as first line treatment in the management of high grade vesicoureteral reflux.

PURPOSE: Endoscopic correction of vesicoureteral reflux has become an established alternative to long-term antibiotic prophylaxis and ureteral reimplantation. A number of tissue augmenting substances have been used for the endoscopic correction of vesicoureteral reflux. We prospectively evaluated the effectiveness of dextranomer/hyaluronic acid copolymer (Deflux) as first line treatment for high grade vesicoureteral reflux. MATERIALS AND METHODS: Between 2001 and 2004, 692 children with a median age of 2.1 years (3 months to 13.7 years) with high grade vesicoureteral reflux underwent endoscopic subureteral injection of Deflux soon after the diagnosis of vesicoureteral reflux was made on the initial voiding cystourethrogram. Vesicoureteral reflux was unilateral in 283 patients and bilateral in 409. Of the 1,101 ureters vesicoureteral reflux was grade II to V in 35 (3.2%), 580 (52.7%), 457 (41.5%) and 29 (2.6%), respectively. The procedure was performed on an outpatient basis. Followup ultrasound and voiding cystourethrogram were performed 3 months after the procedure, and renal and bladder ultrasound was done annually. RESULTS: Reflux resolved after first, second and third endoscopic Deflux injections in 952 (86.5%), 130 (11.8%) and 19 ureters (1.7%), respectively. Followup ultrasound revealed no evidence of delayed vesicoureteral junction obstruction. Of the patients 18 (2.6%) had urinary tract infection during followup after successful vesicoureteral reflux correction. CONCLUSIONS: Endoscopic subureteral injection of Deflux is excellent first line treatment in children with high grade vesicoureteral reflux. This 15-minute outpatient procedure is safe and simple to perform, and it can be easily repeated in failed cases.