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.).

Cryptorchidism: experience and reason.

INTRODUCTION: To characterize our contemporary clinical experience with cryptorchidism. MATERIALS AND METHODS: The records of boys referred for cryptorchidism were reviewed from 2001 to 2011. Data regarding the incidence of retractile testes, testicular ascent, surgical approach and outcomes were tabulated. Follow up was both early (< 12 weeks) and late (> 12 weeks). RESULTS: A total of 1885 patients, or 2593 testes, were identified. Eight hundred and forty-one children (45%) or 1204 testes (46%) were retractile on initial exam-57% bilateral; 187 testes (7%) later 'ascended' on re-examination and underwent surgery--15% bilateral; 1340 (85%) testes were palpable in the inguinal canal and underwent inguinal orchidopexy--98% were successful; 69 (4%) of initially palpable testes were found to be atrophic and removed; 167 (11%) testes were non-palpable and underwent laparoscopy-46 were atrophic and removed; 31 were vanishing; 33 were brought down using an inguinal approach at the same sitting with 97% success; 47 underwent staged Fowler-Stephens orchidopexy (FSO) and 10 underwent non-staged FSO, with 82% and 78% success respectively. All second stages were performed open. CONCLUSIONS: Almost half of children referred for cryptorchidism had retractile testes. Surgery for later ascent was required in 16% of testes judged to be retractile at a median age of 8 years, emphasizing the need for repeat examination. High success rates with inguinal orchidopexy were achieved, even in non-palpable testes. Testes requiring FSO were uncommonly encountered-approximately 5 testes/year or 4% of testes undergoing surgery-and success was achieved in approximately 80%.

Vesicoureteral Reflux and Antibiotic Prophylaxis: Why Cohorts and Methodologies Matter.

PURPOSE: Published cohorts of children with vesicoureteral reflux placed on antibiotic prophylaxis differ in baseline characteristics and methodology. These data have been combined in meta-analyses to derive treatment recommendations. We analyzed these cohorts in an attempt to understand the disparate outcomes reported. MATERIALS AND METHODS: A total of 18 studies were identified from 1987 to 2013. These series retrospectively or prospectively evaluated children with vesicoureteral reflux who were on long-term antibiotic prophylaxis. Presenting demographic data, criteria and methods of evaluation were tabulated. Outcomes were compared, specifically recurrent urinary infections and renal scarring. RESULTS: Significant differences identified in baseline characteristics included gender, circumcision status and reflux grade, and differences in methodology included evaluation of bowel and bladder dysfunction, method of urine collection, definition of urinary infection, measurement of compliance and means of identifying renal scarring. Cohorts with larger numbers of uncircumcised boys had more breakthrough urinary infections. Infection and renal scarring rates were higher in series with higher grades of reflux. Bagged urine specimens were allowed in 6 series, rendering the data suspect. Children with bowel and bladder dysfunction were excluded from 3 cohorts, and bowel and bladder dysfunction was correlated with outcome in only 1 cohort. Compliance was monitored in only 6 studies. CONCLUSIONS: Subpopulations and methodologies vary significantly in published series of children with vesicoureteral reflux on antibiotic prophylaxis. It is inappropriate to combine outcomes data from these series in a meta-analysis, which would serve to blur distinctions between these subpopulations. Broad recommendations or guidelines based on meta-analyses should be viewed with caution.

The RIVUR voiding cystourethrogram pilot study: experience with radiologic reading concordance.

PURPOSE: Two reference radiologists independently review voiding cystourethrograms for the National Institutes of Health sponsored RIVUR (Randomized Intervention for Children with Vesicoureteral Reflux) trial for children with vesicoureteral reflux. A pilot study was required from all clinical centers before enrolling patients. MATERIALS AND METHODS: Digital images were reviewed. Responses were compared and discrepancies adjudicated by teleconference to a final assessment. RESULTS: A total of 75 studies from 19 sites were reviewed. Discrepancies in vesicoureteral reflux grade level were noted on the left and right side in 11 (15%, kappa 0.85) and 12 (16%, kappa 0.83) ureters, respectively. Other areas of disagreement were the presence of paraureteral diverticulum (left 11%, kappa 0.31; right 9%, kappa 0.34), urethral anatomy (15%, kappa 0.33), whether the child voided (8%, kappa 0.21), the presence of ureteral duplication (left 7%, kappa 0.64; right 3%, kappa 0.78) and the presence of bladder trabeculation (5%, kappa 0.32). Of 83 ureters in which reflux was seen there was grade disagreement about 23 (28%). Of 61 ureters initially assessed as grade II or III reflux by both readers, there was disagreement on 9 (15%). Of these 9 discrepancies 7 (78%) were adjudicated to the higher grade (grade III). CONCLUSIONS: Discrepancies in the assessment of intermediate grade vesicoureteral reflux were noteworthy. Recommendations for patients with grade II or III reflux advanced by studies which rely on a single reading, which categorize only grade III or higher reflux as significant, may not be valid.

Antibiotic prophylaxis in pediatric urology: an update.

This article discusses the use of antibiotic prophylaxis in the treatment of three common conditions encountered by the pediatric urologist: 1) children with urinary infection and structurally and neurologically normal urinary tracts; 2) children with vesicoureteral reflux (VUR); and 3) children with prenatally diagnosed ureteropelvic and ureterovesical obstruction. The literature remains unclear and contradictory. Additional significant risk factors for recurrent infection are age, circumcision status in boys, and toileting function. The evidence for the use of prophylaxis is best in those with VUR, although not everyone with VUR must be on medication. In the absence of definitive evidence, the clinician must individualize the treatment of each patient and family.

Laboratory Findings After Urinary Tract Infection and Antimicrobial Prophylaxis in Children With Vesicoureteral Reflux.

It is a common practice to monitor blood tests in patients receiving long-term trimethoprim-sulfamethoxazole (TMP-SMZ) prophylaxis for recurrent urinary tract infections. This multicenter, randomized, placebo-controlled trial enrolled 607 children aged 2 to 71 months with vesicoureteral reflux diagnosed after symptomatic urinary tract infection. Study participants received TMP-SMZ (n = 302) or placebo (n = 305) and were followed for 2 years. Serum electrolytes (n ≥ 370), creatinine (n = 310), and complete blood counts (n ≥ 206) were measured at study entry and at the 24-month study conclusion. We found no significant electrolyte, renal, or hematologic abnormalities when comparing the treatment and placebo groups. We observed changes in several laboratory parameters in both treatment and placebo groups as would normally be expected with physiologic maturation. Changes were within the normal range for age. Long-term use of TMP-SMX had no treatment effect on complete blood count, serum electrolytes, or creatinine. Our findings do not support routine monitoring of these laboratory tests in children receiving long-term TMP-SMZ prophylaxis.

Pediatric pyeloplasty: comparison of literature meta-analysis of laparoscopic and open techniques with open surgery at a single institution.

PURPOSE: We performed a meta-analysis of published series of laparoscopic and open pyeloplasty. We compared these data to open pyeloplasty at our institution using diuretic renography as the indicator for obstruction and postoperative success. MATERIALS AND METHODS: Laparoscopic studies included 19 series published between 1995 and 2007 comprising 346 kidneys. Open pyeloplasty studies included 9 series published between 1998 and 2007 comprising 486 kidneys. Data from our institution included records for 213 patients (224 kidneys). We defined reoperative intervention as unplanned placement of a nephrostomy tube or ureteral stent, balloon dilation or redo pyeloplasty. RESULTS: In the laparoscopic studies 171 cases (49%) were evaluated by preoperative and 137 (40%) by postoperative diuretic renography. Of patients undergoing postoperative diuretic renography 10 (7%) underwent reoperative intervention, including redo pyeloplasty (6, 4%), nephrostomy (3, 2%) and balloon dilation (1, 1%). In the open pyeloplasty studies performed elsewhere 165 cases (34%) were evaluated by preoperative and 230 (47%) by postoperative diuretic renography. Of patients undergoing postoperative diuretic renography redo pyeloplasty was required in 3 (1%). Of 224 cases managed by open pyeloplasty at our institution 215 (96%) had preoperative and postoperative diuretic renography data available. Of these patients 7 (3%) underwent reoperative intervention, including redo pyeloplasty (4, 2%), ureteral stent (2, 1%) and nephrostomy (1, 0.4%). CONCLUSIONS: Most publications do not confirm preoperative obstruction or, following laparoscopic or open pyeloplasty, postoperative success via diuretic renography. While not statistically significant, in the minority of studies with postoperative diuretic renography results the reoperative intervention rate and redo pyeloplasty rate following laparoscopy are approximately double those of open pyeloplasty.

Cost-Utility of Antimicrobial Prophylaxis for Treatment of Children With Vesicoureteral Reflux.

Objective: Antimicrobial prophylaxis for children with vesicoureteral reflux (VUR) reduces recurrences of urinary tract infection (UTI) but requires daily antimicrobials for extended periods. We used a cost-utility model to evaluate whether the benefits of antimicrobial prophylaxis outweigh its risks and, if so, to investigate whether the benefits and risks vary according to grade of VUR. Methods: We compared the cost per quality-adjusted life-year (QALY) gained in four treatment strategies in children aged <6 years diagnosed with VUR after a first UTI, considering these treatment strategies: (1) prophylaxis for all children with VUR, (2) prophylaxis for children with Grade III or Grade IV VUR, (3) prophylaxis for children with Grade IV VUR, and (4) no prophylaxis. Costs and effectiveness were estimated over the patient's lifetime. We used $100,000/QALY gained as the threshold for considering a treatment strategy cost effective. Results: Based on current data and plausible ranges to account for data uncertainty, prophylaxis of children with Grades IV VUR costs $37,903 per QALY gained. Treating children with Grade III and IV VUR costs an additional $302,024 per QALY gained. Treating children with all grades of VUR costs an additional $339,740 per QALY gained. Conclusions: Treating children with Grades I, II, and III VUR with long-term antimicrobial prophylaxis costs substantially more than interventions typically considered economically reasonable. Prophylaxis in children with Grade IV VUR is cost effective.

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.

Reliability of grading of vesicoureteral reflux and other findings on voiding cystourethrography.

INTRODUCTION: Voiding cystourethrography (VCUG) is the modality of choice to diagnose vesicoureteral reflux (VUR). Although grading of VUR is essential for prognosis and clinical decision-making, the inter-observer reliability for grading has been shown to vary substantially. The Randomized Intervention for Children with VesicoUreteral Reflux (RIVUR) trial provides a large cohort of children with VUR to better understand the reliability of VCUG findings. OBJECTIVE: To determine the inter-observer consistency of the grade of VUR and other VCUG findings in a large cohort of children with VUR. STUDY DESIGN: The RIVUR trial is a randomized controlled trial of antimicrobial prophylaxis in children with VUR diagnosed after UTI. Each enrollment VCUG was read by a local clinical (i.e. non-reference) radiologist, and independently by two blinded RIVUR reference radiologists. Reference radiologists' disagreements were adjudicated for trial purposes. The grade of VUR and other VCUG findings were extracted from the local clinical radiologist's report. The unit of analysis included individual ureters and individual participants. We compared the three interpretations for grading of VUR and other VCUG findings to determine the inter-observer reliability. RESULTS: Six-hundred and two non-reference radiology reports from 90 institutions were reviewed and yielded the grade of VUR for 560 left and 524 right ureters. All three radiologists agreed on VUR grade in only 59% of ureters; two of three agreed on 39% of ureters; and all three disagreed on 2% of ureters (Table). Agreement was better (≥92%) for other VCUG findings (e.g. bladder shape "normal"). The non-reference radiologists' grade of VUR differed from the reference radiologists' adjudicated grade by exactly one grade level in 19% of ureters, and by two or more grade levels in 2.2% of ureters. When the participant was the unit of analysis, all three radiologists agreed on the grade of VUR in both ureters in just 43% of cases. DISCUSSION: Our study shows considerable and clinically relevant variability in grading VUR by VCUG. This variability was consistent when comparing non-reference to the adjudicated reference radiologists' assessment and the reference radiologists to each other. This study was limited to children with a history of UTI and grade I-IV VUR and may not be generalizable to all children who have a VCUG. CONCLUSION: The considerable inter-observer variability in VUR grading has both research and clinical implications, as study design, risk stratification, and clinical decision-making rely heavily on grades of VUR.

Variation in the level of detail in pediatric voiding cystourethrogram reports.

INTRODUCTION: Voiding cystourethrogram (VCUG) provides a wealth of data on urinary tract function and anatomy, but few standards exist for reporting VCUG findings. OBJECTIVE: We aimed to assess variability in VCUG reports and to test our hypothesis that VCUG reports from pediatric facilities and pediatric radiologists are more complete than those performed at other facilities or by non-pediatric radiologists. STUDY DESIGN: We analyzed original VCUG reports from children enrolled in the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial. A 23-item checklist was created and used to evaluate reporting of technical (e.g. catheter size), anatomic (e.g. vesicoureteral reflux (VUR) presence and grade, bladder shape), and functional information (e.g. bladder emptying). Radiologists were classified as pediatric or non-pediatric radiologists. Facilities were categorized as to whether they were a free-standing pediatric hospital (FSPH), a pediatric "hospital within a hospital" (PHWH), a non-pediatric hospital (NPH), or an outpatient radiology facility (ORF). Multivariate linear regression was used to analyze factors associated with the completeness of the VCUG reports (percent of items reported from the 23-item checklist). RESULTS: Six-hundred and two VCUGs were performed at 90 institutions. Of those, 76% were read by a pediatric radiologist, and 49% were performed at a FSPH (Table). On average, less than half of the 23 items in our standardized assessment tool were included in VCUG reports (mean 48%, SD 12). The completeness of reports varied by facility type: 51% complete at FSPH (SD 11), 50% at PHWH (SD 10), 36% at NPH (SD 11), and 43% at ORF (SD 8) (p < 0.0001). In multivariate analysis, VCUG reports generated at NPH or ORF had 8% fewer items included (95% CI 3.0-12.8, p < 0.01), and those generated at PHWH did not differ from those generated at FSPH. Reports read by a non-pediatric radiologist had 6% fewer items included (95% CI 3-9.7; p < 0.01) compared with those read by a pediatric radiologist. DISCUSSION: There is substantial underreporting of findings in VCUG reports when assessing a widely represented sample of routine, community-generated reports using an idealized standard. Although VUR was often reported, other crucial anatomic and functional findings of the VCUG were consistently underreported across all facility types. CONCLUSION: Although pediatric radiologist and pediatric hospitals generated more complete VCUG reports compared with those having non-pediatric origins, the differences are small when considering the substantial underreporting of VCUG findings in general. This underscores the opportunities for improvement in reporting of VCUG findings.