Eric Colhoun

ENDOSCOPIC TREATMENT OF VESICOURETERAL REFLUX: 11 TO 17 YEARS OF FOLLOWUP

PURPOSE We review our 17-experience with endoscopic subureteral polytetrafluoroethylene injection for the treatment of primary vesicoureteral reflux in children. MATERIALS AND METHODS We retrospectively reviewed the charts of 258 patients with primary vesicoureteral reflux who were treated with subureteral polytetrafluoroethylene injection from 1984 to 1990. RESULTS The study included 205 girls and 53 boys between 3 months and 14 years old (median age 6 years). Of the patients 92 had unilateral vesicoureteral reflux, 129 had bilateral reflux and 37 had a refluxing duplex system including 6 with bilateral duplex systems. Endoscopic treatment by subureteral polytetrafluoroethylene injection was performed in 393 ureters. Reflux was corrected in 302 ureters (76.8%) after a single injection. Injection failed to stop reflux in 7 ureters (7 patients) and reimplantation was required. Patients were followed from 11 to 17 years with a mean followup plus or minus standard deviation of 13.5 +/- 3.4 years. Four patients were either lost to followup or parents refused to let them undergo voiding cystourethrography. Voiding cystourethrography in 247 patients with 379 ureters revealed that 360 ureters (95%) remain free of reflux whereas reflux recurred in 19 ureters (5%). Of these 19 ureters reflux was grade I or II in 13 for which no treatment was given and reflux was grade III or IV in 6, which required repeat injection. No untoward effects were seen in any of these patients with use of polytetrafluoroethylene as an injectable biomaterial. CONCLUSIONS Endoscopic subureteral polytetrafluoroethylene injection is a simple and effective outpatient procedure for in the treatment of vesicoureteral reflux. No long-term morbidity was observed in our patients with small amounts of injectable polytetrafluoroethylene.

URINARY TRACT INFECTION AND RENAL DAMAGE IN SIBLING VESICOURETERAL REFLUX

PURPOSE Siblings of index patients with vesicoureteral reflux are known to have an increased incidence of reflux. Previously reported studies have evaluated vesicoureteral reflux in asymptomatic siblings of children who were previously proved to have reflux. We determine the incidence and nature of vesicoureteral reflux in symptomatic siblings of children with documented vesicoureteral reflux. MATERIALS AND METHODS Between January 1990 and December 1996, 624 patients were diagnosed with vesicoureteral reflux during the investigation of documented urinary tract infections. All patients were evaluated for reflux by contrast voiding cystourethrography and reflux was graded according to the international reflux study. 99mTechnetium dimercapto-succinic acid nuclear renal scans were performed to detect renal scarring. The medical records and voiding cystourethrograms of the 624 consecutive patients with vesicoureteral reflux were retrospectively reviewed to identify siblings with vesicoureteral reflux. RESULTS Vesicoureteral reflux was noted in 85 siblings (134 refluxing ureters) of the 624 index patients (13.6%), including 1 and 2 siblings of 38 and 3 patients, respectively. Mean age at presentation of the 37 boys and 48 girls was 2.5 years. Reflux was unilateral in 36 siblings and bilateral in 49. Reflux was grades I to V in 8, 9, 51, 55 and 11 ureters, respectively. Nuclear scan revealed reflux nephropathy in 22 of the 77 tested siblings (28.5%). CONCLUSIONS When vesicoureteral reflux is discovered in symptomatic siblings, it is usually high grade and associated with a higher incidence of reflux nephropathy. Of further interest are the findings that refluxing symptomatic siblings of index patients are usually younger and boys are as commonly affected as girls. Screening for vesicoureteral reflux in asymptomatic siblings is recommended to decrease the incidence of reflux nephropathy.

Renal Parenchymal Damage in Male Infants with High Grade Vesicoureteral Reflux Diagnosed After the First Urinary Tract Infection

PURPOSE Vesicoureteral reflux during infancy is found mainly in males, and it is of high grade and often bilateral. The higher predominance of male infants is reported in series when the reflux is diagnosed prenatally and when it is detected after urinary tract infection. Renal parenchymal damage may already be present at birth before any episode of urinary tract infection or acquired after a febrile urinary tract infection. We evaluate the incidence of renal damage in a large series of male infants with high grade vesicoureteral reflux diagnosed after the first urinary tract infection. MATERIALS AND METHODS We reviewed the medical and radiological records of 141 consecutive male infants 3 weeks to 1 year old (mean age 5.8 months) who were diagnosed with high grade (III to V) vesicoureteral reflux on voiding cystourethrography during 1984 to 2000 following hospitalization for the first febrile urinary tract infection. A total of 127 (90%) patients underwent technetium dimercapto-succinic acid scan to evaluate renal damage 3 to 6 months after the initial infection. RESULTS Vesicoureteral reflux was unilateral in 46 infants and bilateral in the remaining 95, comprising 236 ureters. Reflux was grade III in 79 ureters, IV in 114 and V in 43. Renal parenchymal damage was detected in 56 (44%) of the 127 infants on dimercapto-succinic acid scan, and was bilateral in 18 and unilateral in the 38, representing 74 renal refluxing units. Renal damage was mild (greater than 40% uptake) in 47 units, moderate (less than 40% and greater than 20% uptake) in 22 U and severe (less than 20% uptake) in 5 U. CONCLUSIONS This study shows that nearly half of the male infants with high grade reflux who present with the first febrile urinary tract infection have renal parenchymal damage. This high incidence of renal damage may be explained by the coexistence of the 3 risk factors of gender, urinary tract infection and high grade vesicoureteral reflux.

Single center experience with endoscopic subureteral dextranomer/hyaluronic acid injection as first line treatment in 1,551 children with intermediate and high grade vesicoureteral reflux.

PURPOSE In recent years the endoscopic injection of dextranomer/hyaluronic acid has become an established alternative to long-term antibiotic prophylaxis and the surgical management of vesicoureteral reflux. We determined the safety and effectiveness of the endoscopic injection of dextranomer/hyaluronic acid as first line treatment for high grade vesicoureteral reflux. MATERIALS AND METHODS Between 2001 and 2010, 1,551 children (496 male, 1,055 female, median age 1.6 years) underwent endoscopic correction of intermediate and high grade vesicoureteral reflux using dextranomer/hyaluronic acid soon after the diagnosis of vesicoureteral reflux on initial voiding cystourethrogram. Vesicoureteral reflux was unilateral in 761 children and bilateral in 790. Renal scarring was detected in 369 (26.7%) of the 1,384 patients who underwent dimercapto-succinic acid imaging. Reflux grade in the 2,341 ureters was II in 98 (4.2%), III in 1,340 (57.3%), IV in 818 (34.9%) and V in 85 (3.6%). Followup ultrasound and voiding cystourethrogram were performed 3 months after the outpatient procedure, and renal ultrasound was performed annually thereafter. Patients were followed for 3 months to 10 years (median 5.6 years). RESULTS Vesicoureteral reflux resolved after the first, second and third endoscopic injection of dextranomer/hyaluronic acid in 2,039 (87.1%), 264 (11.3%) and 38 (1.6%) ureters, respectively. Febrile urinary tract infections developed during followup in 69 (4.6%) patients. None of the patients in the series needed reimplantation of ureters or experienced any significant complications. CONCLUSIONS Our results confirm the safety and efficacy of the endoscopic injection of dextranomer/hyaluronic acid in the eradication of high grade vesicoureteral reflux. We recommend this 15-minute outpatient procedure as the first line of treatment for high grade vesicoureteral reflux.

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.

Renal parenchymal damage in sibling vesicoureteric reflux

Aim: To compare the incidence of renal damage in siblings of patients with vesicoureteric reflux (VUR) who presented with a documented history of urinary tract infection (UTI) with asymptomatic siblings who were diagnosed with reflux during a screening programme for hereditary VUR. Methods: Medical and radiological records of the VUR patients (1990–2000) were examined for age, gender, mode of presentation, reflux grade and renal damage. Results: VUR was noted in 226 siblings (352 ureters) in 107 families. Of the 119 siblings of index patients, 64 were investigated for a documented UTI and 55 with no history of UTI were detected during screening for sibling reflux. Dimercaptosuccinic acid scan revealed reflux nephropathy in 25 (26%) of the 97 renal refluxing units (RRU) of siblings who presented with a UTI and in 6 (7%) of the 89 RRU of asymptomatic siblings who underwent screening voiding cystourethrography (p= 0.0006). Mild renal damage was present in 20 (21%) RRU of siblings with UTI and in 2 (2%) RRU of the screened siblings (p < 0.001). Moderate to severe renal damage was present in 5 (5%) RRU of siblings with UTI and in 4 (4%) RRU of the screened siblings (p > 0.05).

Prevalence and predictors of renal functional abnormalities of high grade vesicoureteral reflux.

PURPOSE The association of vesicoureteral reflux, febrile urinary tract infections and renal parenchymal damage is well recognized. We determined the prevalence and predictors of renal functional abnormalities in children with high grade vesicoureteral reflux. MATERIALS AND METHODS We retrospectively reviewed the medical records and dimercapto-succinic acid scans of 774 consecutive children with primary high grade vesicoureteral reflux (grade IV-V) seen at our institution between 1998 and 2011. For multivariate analysis we analyzed variables associated with renal functional abnormalities, such as presentation history, age, gender and reflux grade, in a logistic regression model. RESULTS Of the children 698 (90%) and 76 (10%) had grade IV and V reflux, respectively. Dimercapto-succinic acid scans revealed renal functional abnormalities in 291 children (37.6%), including 240 (34%) with grade IV and 51 (67%) with grade V reflux. Univariate analysis showed that age greater than 1 year (OR 2.95, p <0.001), grade V reflux (OR 4.09, p <0.001) and preoperative bladder/bowel dysfunction (OR 2.94, p = 0.026) were significant predictors of renal functional abnormalities. Multivariate analysis showed that age greater than 1 year (OR 3.45, p = 0.001) and grade V reflux (OR 5.89, p <0.001) were the most significant independent predictors of such abnormalities. CONCLUSIONS There is an increased risk of renal functional abnormalities in children older than 1 year and those with grade V vesicoureteral reflux. Patients with a history of bladder/bowel dysfunction are also at greater risk for such abnormalities. The early detection and treatment of high grade vesicoureteral reflux may prevent acquired renal parenchymal damage and limit the progression of renal damage in patients with congenital reflux nephropathy.

Megaprepuce Associated with Vesicoureteric Reflux

Objective: To describe 4 patients in whom megaprepuce was associated with vesicoureteric reflux (VUR). Patients and Methods: Four boys aged 6, 4, 5 and 7 months, respectively, presented with dribbling of urine, gross penile swelling and inability to void spontaneously. The first 3 patients had a history of documented urinary tract infection. Micturating cystourethrogram (MCUG) revealed grade III VUR on the right in the first patient, grade V on the left in the second patient, grade III on the right and grade IV in both moieties of left duplex system in the third patient and bilateral grade III in the fourth patient. All patients underwent circumcision. Results: Follow–up MCUG demonstrated complete resolution of VUR in 2 patients after circumcision. One patient with bilateral VUR showed resolution of VUR on right side but persistence of VUR into the lower moiety of left duplex system after circumcision. Vesicoureteric reflux was downgraded from grade 5 to grade 3 after circumcision in one patient. Conclusion: These cases demonstrate for the first time the association of megaprepuce with VUR. VUR associated with megaprepuce is usually resolved after circumcision.

Endoscopic Injection of Dextranomer/Hyaluronic Acid as First Line Treatment in 851 Consecutive Children with High Grade Vesicoureteral Reflux: Efficacy and Long-Term Results

Purpose: Endoscopic injection of dextranomer/hyaluronic acid is widely acknowledged as first line treatment of lower grade vesicoureteral reflux. We demonstrate its long‐term efficacy and safety in eradicating high grade reflux. Materials and Methods: A total of 518 girls and 333 boys with a median age of 2.3 years (range 2 months to 13.7 years) underwent endoscopic correction of high grade vesicoureteral reflux using dextranomer/hyaluronic acid. Reflux was unilateral in 415 cases and bilateral in 436, comprising 1,287 refluxing units. Reflux was grade IV in 1,153 ureters (89.6%) and grade V in 134 (10.4%). 99mTechnetium‐dimercaptosuccinic acid scintigraphy identified renal scarring in 317 patients (37.3%). Followup ultrasound and voiding cystourethrogram were performed 3 months after intervention and renal ultrasound yearly thereafter. Median followup was 8.5 years (range 6 months to 16 years). Results: Overall resolution rate after the first endoscopic injection was 69.5% (895 of 1,287 cases), with resolution in 70.4% of grade IV and 61.9% of grade V cases. Reflux resolved after a second injection in 259 cases (20.1%) and after a third injection in 133 (10.4%). Persistent reflux after initial treatment was significantly more common in patients younger than age 1 year and in individuals with renal scarring. No significant postoperative complications were observed and no patient required ureteral reimplantation. Following reflux resolution febrile urinary tract infection developed in 43 children (5.1%), including 24 (55.8%) during the first year, 15 (34.9%) during the second year and 4 (9.3%) during year 3 or later. Of these patients 6 had reflux recurrence and 8 had neocontralateral grade III reflux, which was successfully treated with a single endoscopic injection of dextranomer/hyaluronic acid. Conclusions: Endoscopic injection of dextranomer/hyaluronic acid is an efficient and safe long‐term treatment for grade IV and V vesicoureteral reflux, and can easily be repeated in patients with treatment failure with a high subsequent resolution rate.

Renal Cortical Abnormalities in Siblings of Index Patients With Vesicoureteral Reflux

OBJECTIVE: Screening siblings of index patients with vesicoureteral reflux (VUR) has been proposed to identify children who are at risk for renal damage. However, screening siblings for VUR remains controversial. We investigated the prevalence of VUR and renal cortical abnormalities in the sibling population in a large cohort of families with VUR. METHODS: Between 1998 and 2012, parents of index patients with grade III to V VUR were asked permission to screen siblings <6 years of age for VUR. Siblings were divided into 2 groups: siblings with a documented history of a previous urinary tract infection (UTI) and siblings who were screened for VUR and never had a UTI. A logistic regression model was used to determine independent risk factors associated with renal cortical abnormalities such as history of presentation, age, gender, and grade of VUR. RESULTS: There were 318 siblings in 275 families in the study. VUR was found after screening in 190 (60%) siblings and after a UTI in 128 (40%). Multivariate analysis revealed that siblings who had a previous UTI (odds ratio: 3.38), siblings with high grade reflux (odds ratio: 3.62), and siblings over 1 year of age (odds ratio: 2.84) were the most significant independent risk factors associated with renal cortical abnormalities. CONCLUSIONS: There is increased risk of renal cortical abnormalities in siblings with a previous UTI, siblings with high-grade VUR, and siblings over age 1 year. This information may help to counsel parents about the risk of VUR and reflux nephropathy in familial VUR.