Antimicrobial prophylaxis for children with vesicoureteral reflux.

BACKGROUND: Children with febrile urinary tract infection commonly have vesicoureteral reflux. Because trial results have been limited and inconsistent, the use of antimicrobial prophylaxis to prevent recurrences in children with reflux remains controversial. METHODS: In this 2-year, multisite, randomized, placebo-controlled trial involving 607 children with vesicoureteral reflux that was diagnosed after a first or second febrile or symptomatic urinary tract infection, we evaluated the efficacy of trimethoprim-sulfamethoxazole prophylaxis in preventing recurrences (primary outcome). Secondary outcomes were renal scarring, treatment failure (a composite of recurrences and scarring), and antimicrobial resistance. RESULTS: Recurrent urinary tract infection developed in 39 of 302 children who received prophylaxis as compared with 72 of 305 children who received placebo (relative risk, 0.55; 95% confidence interval [CI], 0.38 to 0.78). Prophylaxis reduced the risk of recurrences by 50% (hazard ratio, 0.50; 95% CI, 0.34 to 0.74) and was particularly effective in children whose index infection was febrile (hazard ratio, 0.41; 95% CI, 0.26 to 0.64) and in those with baseline bladder and bowel dysfunction (hazard ratio, 0.21; 95% CI, 0.08 to 0.58). The occurrence of renal scarring did not differ significantly between the prophylaxis and placebo groups (11.9% and 10.2%, respectively). Among 87 children with a first recurrence caused by Escherichia coli, the proportion of isolates that were resistant to trimethoprim-sulfamethoxazole was 63% in the prophylaxis group and 19% in the placebo group. CONCLUSIONS: Among children with vesicoureteral reflux after urinary tract infection, antimicrobial prophylaxis was associated with a substantially reduced risk of recurrence but not of renal scarring. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; RIVUR ClinicalTrials.gov number, NCT00405704.).

Nocturnal enuresis: an approach to assessment and treatment.

On the basis of strong evidence, although primary monosymptomatic nocturnal enuresis (PMNE) is common and most children will outgrow the condition spontaneously, the psychological effect to the child can be significant and represents the main reason for treatment of these children. On the basis of international consensus panels, treatment of PMNE should be targeted toward the specific type of bedwetting patterns the child has, using bladder diary, sleep history, and daytime elimination concerns as a guide (Table 3). On the basis of international consensus panels, it is important for the primary care physician to be able to differentiate children with PMNE from children with nonmonosymptomatic nocturnal enuresis (NMNE) and secondary nocturnal enuresis. On the basis of international consensus panels, children with NMNE should have their underlying voiding or stool problem addressed before initiation of therapy for the nocturnal enuresis. On the basis of strong evidence, both the bedwetting alarm and desmopressin are considered first-line therapy for children with PMNE.

Parental preferences in the management of vesicoureteral reflux.

PURPOSE: Considering that there are few absolute indications for the timing and type of surgical correction of vesicoureteral reflux, we objectively measured parental choice in how the child's vesicoureteral reflux should be managed. MATERIALS AND METHODS: We prospectively identified patients 0 to 18 years old with any grade of newly diagnosed vesicoureteral reflux. All races and genders were included, and non-English speakers were excluded from analysis. Parents were shown a video presented by a professional actor that objectively described vesicoureteral reflux and the 3 treatment modalities of antibiotic prophylaxis, open ureteral reimplantation and endoscopic treatment. Then they completed a questionnaire regarding their preference for initial management, and at hypothetical followup points of 18, 36 and 54 months. Consultation followed with the pediatric urologist who was blinded to the questionnaire results. RESULTS: A total of 86 girls and 15 boys (150 refluxing units) were enrolled in the study. Mean patient age was 2.6 years old. Preferences for initial treatment were antibiotic prophylaxis in 36, endoscopic surgery in 26, open surgery in 11, unsure in 26 and no response in 2. Among those initially selecting antibiotic prophylaxis, after 18 months the preference was for endoscopic treatment, but after 36 and 54 months preferences trended toward open surgery. After consultation with the pediatric urologist 68 parents chose antibiotic prophylaxis. CONCLUSIONS: Our data show that antibiotic prophylaxis is preferred as the initial therapy for vesicoureteral reflux by 35.6% of parents. However, given persistent vesicoureteral reflux, preferences shifted toward surgery. With time the preference for open surgery increased and the preference for endoscopic surgery decreased.

Febrile urinary tract infection, vesicoureteral reflux, and renal scarring: current controversies in approach to evaluation.

The ideal approach to the radiological evaluation of children with urinary tract infection (UTI) is in a state of confusion. The conventional bottom-up approach, with its focus on the detection of upper and lower urinary tract abnormalities, including vesicoureteral reflux, has been challenged by the top-down approach, which focuses on confirming the diagnosis of acute pyelonephritis before more invasive imaging is considered. Controversies abound regarding which approach may best assess the ultimate risk for reflux-related renal scarring. Evolving practices motivated by the emerging evidence, the desire to minimize unnecessary interventions, as well as improve compliance with recommended testing, have added to the current controversies. Recent guideline updates and ongoing clinical trials hopefully will help in addressing some of these concerns.

Pediatric Vesicoureteral Reflux Guidelines Panel Summary Report: Clinical Practice Guidelines for Screening Siblings of Children With Vesicoureteral Reflux and Neonates/Infants With Prenatal Hydronephrosis.

PURPOSE: The American Urological Association established the Vesicoureteral Reflux Guideline Update Committee in July 2005 to update the management of primary vesicoureteral reflux in children guideline. The Panel defined the task into 5 topics pertaining to specific vesicoureteral reflux management issues, which correspond to the management of 3 distinct index patients and the screening of 2 distinct index patients. This report summarizes the existing evidence pertaining to screening of siblings and offspring of index patients with vesicoureteral reflux and infants with prenatal hydronephrosis. From this evidence clinical practice guidelines are developed to manage the clinical scenarios insofar as the data permit. MATERIALS AND METHODS: The Panel searched the MEDLINE(R) database from 1994 to 2008 for all relevant articles dealing with the 5 chosen guideline topics. The database was reviewed and each abstract segregated into a specific topic area. Exclusions were case reports, basic science, secondary reflux, review articles and not relevant. The extracted article to be accepted should have assessed a cohort of children, clearly stating the number of children undergoing screening for vesicoureteral reflux. Vesicoureteral reflux should have been diagnosed with a cystogram and renal outcomes assessed by nuclear scintigraphy. The screening articles were extracted into data tables developed to evaluate epidemiological factors, patient and renal outcomes, and results of treatment. The reporting of meta-analysis of observational studies elaborated by the MOOSE group was followed. The extracted data were analyzed and formulated into evidence-based recommendations regarding the screening of siblings and offspring in index cases with vesicoureteral reflux and infants with prenatal hydronephrosis. RESULTS: In screened populations the prevalence of vesicoureteral reflux is 27.4% in siblings and 35.7% in offspring. Prevalence decreases at a rate of 1 screened person every 3 months of age. The prevalence is the same in males and females. Bilateral reflux prevalence is similar to unilateral reflux. Grade I-II reflux is estimated to be present in 16.7% and grade III-V reflux in 9.8% of screened patients. The estimate for renal cortical abnormalities overall is 19.3%, with 27.8% having renal damage in cohorts of symptomatic and asymptomatic children combined. In asymptomatic siblings only the rate of renal damage is 14.4%. There are presently no randomized, controlled trials of treated vs untreated screened siblings with vesicoureteral reflux to evaluate health outcomes as spontaneous resolution, decreased rates of urinary infection, pyelonephritis or renal scarring. In screened populations with prenatal hydronephrosis the prevalence of vesicoureteral reflux is 16.2%. Reflux in the contralateral nondilated kidney accounted for a mean of 25.2% of detected cases for a mean prevalence of 4.1%. In patients with a normal postnatal renal ultrasound the prevalence of reflux is 17%. The prenatal anteroposterior renal pelvic diameter was not predictive of reflux prevalence. A diameter of 4 mm is associated with a 10% to 20% prevalence of vesicoureteral reflux. The prevalence of reflux is statistically significantly greater in females (23%) than males (16%) (p=0.022). Reflux grade distribution is approximately a third each for grades I-II, III and IV-V. The estimate of renal damage in screened infants without infection is 21.8%. When stratified by reflux grade renal damage was estimated to be present in 6.2% grade I-III and 47.9% grade IV-V (p <0.0001). The risk of urinary tract infection in patients with and without prenatal hydronephrosis and vesicoureteral reflux could not be determined. The incidence of reported urinary tract infection in patients with reflux was 4.2%. CONCLUSIONS: The meta-analysis provided meaningful information regarding screening for vesicoureteral reflux. However, the lack of randomized clinical trials for screened patients to assess clinical health outcomes has made evidence-based guideline recommendations difficult. Consequently, screening guidelines are based on present practice, risk assessment, meta-analysis results and Panel consensus.

Summary of the AUA Guideline on Management of Primary Vesicoureteral Reflux in Children.

PURPOSE: The American Urological Association established the Vesicoureteral Reflux Guideline Update Committee in July 2005 to update the management of primary vesicoureteral reflux in children guideline. The Panel defined the task into 5 topics pertaining to specific vesicoureteral reflux management issues, which correspond to the management of 3 distinct index patients and the screening of 2 distinct index patients. This report summarizes the existing evidence pertaining to children with diagnosed reflux including those young or older than 1 year without evidence of bladder and bowel dysfunction and those older than 1 year with evidence of bladder and bowel dysfunction. From this evidence clinical practice guidelines were developed to manage the clinical scenarios insofar as the data permit. MATERIALS AND METHODS: The Panel searched the MEDLINE(R) database from 1994 to 2008 for all relevant articles dealing with the 5 chosen guideline topics. The database was reviewed and each abstract segregated into a specific topic area. Exclusions were case reports, basic science, secondary reflux, review articles and not relevant. The extracted article to be accepted should have assessed a cohort of children with vesicoureteral reflux and a defined care program that permitted identification of cohort specific clinical outcomes. The reporting of meta-analysis of observational studies elaborated by the MOOSE (Meta-analysis Of Observational Studies in Epidemiology) group was followed. The extracted data were analyzed and formulated into evidence-based recommendations. RESULTS: A total of 2,028 articles were reviewed and data were extracted from 131 articles. Data from 17,972 patients were included in this analysis. This systematic meta-analysis identified increasing frequency of urinary tract infection, increasing grade of vesicoureteral reflux and presence of bladder and bowel dysfunction as unique risk factors for renal cortical scarring. The efficacy of continuous antibiotic prophylaxis could not be established with current data. However, its purported lack of efficacy, as reported in selected prospective clinical trials, also is unproven owing to significant limitations in these studies. Reflux resolution and endoscopic surgical success rates are dependent upon bladder and bowel dysfunction. The Panel then structured guidelines for clinical vesicoureteral reflux management based on the goals of minimizing the risk of acute infection and renal injury, while minimizing the morbidity of testing and management. These guidelines are specific to children based on age as well as the presence of bladder and bowel dysfunction. Recommendations for long-term followup based on risk level are also included. CONCLUSIONS: Using a structured, formal meta-analytic technique with rigorous data selection, conditioning and quality assessment, we attempted to structure clinically relevant guidelines for managing vesicoureteral reflux in children. The lack of robust prospective randomized controlled trials limits the strength of these guidelines but they can serve to provide a framework for practice and set boundaries for safe and effective practice. As new data emerge, these guidelines will necessarily evolve.

Pressure, fluid and anatomical characteristics of abdominoscrotal hydroceles in infants.

PURPOSE: Abdominoscrotal hydrocele is a poorly understood entity and multiple theories attempt to explain its occurrence. To our knowledge the factors contributing to the formation of abdominoscrotal hydrocele are unknown, as are its cellular, biochemical and hydrostatic properties. We prospectively evaluated abdominoscrotal hydrocele at surgery to define its cause and its effects on the testicle. MATERIALS AND METHODS: Six patients (9 abdominoscrotal hydroceles) were prospectively evaluated at surgery. Hydrocele volume was recorded as well as simultaneous hydrocele and bladder pressure. Fluid at surgery was sent for biochemical and cellular analysis. Testicular and epididymal abnormalities were noted and testicular length was measured. All abdominoscrotal hydroceles were exteriorized and excised. Processus vaginalis patency was documented at repair. RESULTS: Mean patient age was 7.17 months (range 5 to 12). The mean volume recorded was 212.78 ml (range 80 to 320). Mean corrected hydrocele pressure was 15.44 cm H(2)O (range 7 to 28). Mean testicular length was 3.6 cm (range 2.2 to 5.5). All patients had epididymal anomalies and 2 of the 3 unilateral abdominoscrotal hydroceles had abnormal contralateral scrotal findings. In no case was a peritoneal communication identified. Fluid analysis revealed a high protein concentration (mean 4.94 gm/dl), low triglyceride concentration (mean 20.29 mg/dl) and lactate dehydrogenase levels comparable to those in normal serum (mean 99.14 U/l). Cytological analysis revealed a sterile, low cellularity fluid with a macrophage predominance (mean 84.71%). CONCLUSIONS: Abdominoscrotal hydrocele occurs as a result of increased intraluminal pressure confined in a proximal closed processus vaginalis. Increased hydrocele pressure allows expansion into the retroperitoneal space through the internal inguinal ring. This increased pressure is associated with testicular elongation and epididymal abnormalities. The exudative fluid is of a noninfectious etiology and it suggests an altered filtration process. To our knowledge the effects on future fertility are unknown.

Interobserver variability for interpretation of DMSA scans in the RIVUR trial.

INTRODUCTION: Technetium-99m dimercaptosuccinic acid (DMSA) renal scans are used in the diagnosis of renal scarring. In the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial that randomized 607 children, DMSA renal scans were used for evaluating the presence and the severity of renal scarring. OBJECTIVE: The aim was to determine interobserver variability in reporting of DMSA renal scans in the RIVUR trial. STUDY DESIGN: We compared DMSA renal scan reports for renal scarring and acute pyelonephritis from all non-reference local radiologists (ALRs) at study sites with adjudicated as well as non-adjudicated reports from two reference radiologists (RRs) of the RIVUR trial. Two-way comparisons of concordant and discrepant responses were analyzed using an unweighted kappa statistic between the ALR and the adjudicated RR interpretations. All analyses were performed using SAS v 9.4 (SAS institute 2015) and significance was determined at the 0.05 level. RESULTS: Of the 2872 kidneys evaluated, adjudicated RR reports had 119 (4%) kidneys with renal scarring compared with 212 (7%) by the ALRs. For 79% kidneys the grading for scarring reported by ALRs was either upgraded (24%) or downgraded (55%) by RRs. For acute pyelonephritis (n = 2924), adjudicated RR reports had 85 (3%) kidneys with pyelonephritis compared with 151 (5%) by the ALRs. For 85% kidneys, the grading for pyelonephritis reported by the ALRs was either upgraded (28%) or downgraded (57%) by the RRs. A three-way comparison revealed that all three (RR1, RR2, and ALR) agreed over presence of renal scarring in 19% cases and two of the three agreed in 80% cases. The respective numbers for pyelonephritis were 13% and 84%. The agreement rate for all DMSA scan reports between the RRs and the ALRs was 93%. DISCUSSION: The study revealed significant interobserver variability in the reporting of abnormal DMSA renal scans compared with the previously published studies. A noteworthy limitation was a lack of uniformity in local reporting of the scans. CONCLUSIONS: Our study highlights the need for optimizing the clinical yield of DMSA renal scans by more specific guidelines, particularly for standardized and uniform interpretation.

Endoscopic treatment for vesicoureteral reflux: how important is technique?

PURPOSE: Endoscopic dextranomer/hyaluronic acid (Dx/HA) injection by subureteric transurethral injection (STING) or hydrodistention implantation technique (HIT) for treatment of vesicoureteral reflux (VUR) has variable results with HIT reporting better outcomes. We determined outcomes with each technique comparing reflux resolution rates and evaluating predictors of treatment success and failure. METHODS: Univariate and multivariate analysis compared 163 patients (246 ureters) who underwent a single endoscopic Dx/HA injection from December 2001 to April 2010. Data on pre, peri, and post-operative variables were prospectively collected. Resolution was defined as no reflux on voiding cystourethrogram (VCUG) at 3 month follow up. Calculated ellipsoid volume (CEV) of Dx/HA mounds was defined as (4/3π(height/2) × (length/2) × (width/2)) based on post-operative ultrasound dimensions. RESULTS: Ureter resolution was 79.75% and 80.84% for STING and HIT, respectively (p = 0.86). Patient resolution was 70.0% and 74.3% for STING and HIT, respectively (p = 0.57). Multivariate ureter analysis revealed lower pre-operative grade (p = 0.004) and injected Dx/HA volume 0.80-1.00 mL (p = 0.039) as predictors of success. CEV <0.20 mL (p = 0.002) and CEV/injected-volume <25% (p = 0.006) were predictors of failure. Volcano morphology (p = 0.004) and lower pre-op grade (p = 0.015) were predictors of success for STING and HIT, respectively. CONCLUSIONS: We found no differences in ureter or patient resolution between endoscopic Dx/HA injection techniques STING or HIT. Lower pre-operative grade and moderated Dx/HA volume were predictors of success regardless of technique.

Subureteral injection of Deflux for correction of reflux: analysis of factors predicting success.

OBJECTIVES: To review, prospectively, our experience with endoscopic Deflux injection and evaluate the volume injected, grade, endoscopic appearance after injection, and presence or absence of voiding dysfunction as predictors of success. Subureteral injection of dextranomer/hyaluronic acid copolymer (Deflux) has become an effective treatment of vesicoureteral reflux. METHODS: A total of 52 patients (50 females and 2 males; 80 ureters) were treated with a single subureteral injection of Deflux. The mean patient age was 7.6 years (range 14 months to 22 years). The presence or absence of voiding dysfunction was evaluated with a preoperative questionnaire and patient history. The volume of Deflux injected in each ureter was recorded. The endoscopic appearance after injection was recorded as "volcano" or "other." Success was defined as no reflux on postoperative voiding cystourethrography. RESULTS: The success rate by grade of reflux in individual ureters was 82%, 84%, 78%, and 73% for grade 1, 2, 3, and 4 vesicoureteral reflux, respectively. No statistically significant difference was found in the cure rate by grade (P = 0.76). The overall cure rate by ureter was 80% and by patient was 71%. New contralateral reflux developed in 12.5% of patients. No statistically significant difference was found in the cure rate with respect to the volume injected or the presence or absence of voiding dysfunction. The ureteral cure rate with volcano and alternate morphology was 87% and 53%, respectively (P = 0.004). CONCLUSIONS: Mound morphology was the only statistically significant predictor of a successful outcome, with an associated cure rate of 87%. Concomitant voiding dysfunction did not have an adverse effect on the cure rate. In our experience, no statistically significant difference was found in the cure rate for grades 1 through 4 vesicoureteral reflux after a single injection of Deflux.

Laser incision of ureterocele in the pediatric patient.

PURPOSE: We evaluated the effectiveness of initial laser transurethral incision of ureterocele for relieving obstruction, prevention of infection and need for subsequent surgery. MATERIALS AND METHODS: We reviewed the medical records and imaging studies of 30 children with ureterocele treated between 1995 and 2000. Of 30 children 14 underwent initial transurethral laser incision of the ureterocele. Records and images were evaluated for mode of presentation, ureterocele location, thickness, and decompression, and relief of obstruction. The incidence of urinary tract infection, new onset vesicoureteral reflux, upper segment renal function and need for subsequent surgery after incision was investigated. RESULTS: There were 5 boys and 9 girls in our series. Mean patient age at presentation was 17.5 months. There were 12 patients who had ectopic and 2 orthotopic ureteroceles. Ureterocele was defined as thick if ultrasound measurement was 4 mm. or greater. Thick ureterocele was present in 4 (28%) patients. All patients had ultrasound evidence of decompression of the ureterocele and upper tract with 1 treatment. Urinary infection risk was 0.015 per month of followup after incision. Vesicoureteral reflux was present in 8 of 12 (67%) ectopic systems before incision and 9 of 10 (90%) after. None had resolved reflux during followup. Upper pole renal function was assessed by renal scan and/or renal ultrasound. Upper pole function or increased cortical thickness was documented in 9 of 11 (82%) patients. Endoscopic laser incision was the only treatment required in 4 of 14 (28%) patients, including 2 with orthotopic and 2 ectopic ureteroceles. Of 14 patients 5 (36%) had undergone definitive surgery and 5 were followed. CONCLUSIONS: Endoscopic laser incision of ureterocele allows a precise incision and decompression of the ureterocele with 1 treatment. Laser incision of ureterocele should be considered as the initial treatment in most patients.