The urological evaluation and management of neurogenic bladder in children and adolescents-what every pediatric nephrologist needs to know.

Neurogenic bladder (NGB) is an encompassing term that includes multiple causes of bladder dysfunction linked to a congenital or acquired neurological condition that adversely impacts the innervation of the lower urinary tract. Multiple static or progressive conditions can be associated with NGB in pediatric and adolescent patients. Currently, spinal dysraphism (i.e., spina bifida) is one of the most common etiologies, which occurs in 3-4 per 10,000 live births in developed nations. Abnormal bladder dynamics can lead to kidney damage secondary to high pressures or recurrent infections, as well as urinary incontinence. The current management paradigm centers on a proactive approach to preserving kidney function and achieving continence through behavioral, pharmacological, and surgical means. This educational review highlights the key components of urological management to maximize collaboration with pediatric nephrologists.

Trends in Management of Fetuses with Suspected Lower Urinary Tract Obstruction (LUTO): A High-Risk Fetal and Pediatric Center Experience in a Universal-Access-to-Care System.

INTRODUCTION: Neonates with lower urinary tract obstruction (LUTO) experience high morbidity and mortality associated with the development of chronic kidney disease. The prenatal detection rate for LUTO is less than 50%, with late or missed diagnosis leading to delayed management and long-term sequelae in the remainder. We aimed to explore the trends in prenatal detection and management at a high-risk fetal center and determine if similar trends of postnatal presentations were noted for the same period. METHODS: Prenatal and postnatal LUTO databases from a tertiary fetal center and its associated pediatric center between 2009 and 2021 were reviewed, capturing maternal age, gestational age (GA) at diagnosis, and rates of termination of pregnancy (TOP). Time series analysis using autocorrelation was performed to investigate time trend changes for prenatally suspected and postnatally confirmed LUTO cases. RESULTS: A total of 161 fetuses with prenatally suspected LUTO were identified, including 78 terminations. No significant time trend was found when evaluating the correlation between time periods, prenatal suspicion, and postnatal confirmation of LUTO cases (Durbin-Watson [DW] = 1.99, p = 0.3641 and DW = 2.86, p = 0.9113, respectively). GA at referral was 20.0 weeks (interquartile range [IQR] 12, 35) and 22.0 weeks (IQR 13, 37) for TOP and continued pregnancies (p < 0.0001). GA at initial ultrasound was earlier in terminated fetuses compared to continued (20.0 [IQR 12, 35] weeks vs. 22.5 [IQR 13, 39] weeks, p < 0.0001). While prenatal LUTO suspicion remained consistently higher than postnatal presentations, the rates of postnatal presentations and terminations remained stable during the study years (p = 0.7913 and 0.2338), as were GA at TOP and maternal age at diagnosis (p = 0.1710 and 0.1921). CONCLUSION: This study demonstrated that more severe cases of LUTO are referred earlier and are more likely to undergo TOP. No significant trend was detected between time and prenatally suspected or postnatally confirmed LUTO, highlighting the need for further studies to better delineate factors that can increase prenatal detection.

The Toronto nomogram: A Bayesian meta-regression derived prenatal ultrasound index to predict lower urinary tract obstruction and prune belly syndrome.

INTRODUCTION: A nomogram for predicting the diagnosis of lower urinary tract obstruction (LUTO) based on an antenatal ultrasound index generated from a Bayesian Meta-regression analysis has been in development and noted with superior diagnostic accuracy compared to the keyhole sign (KHS). We aim to assess the accuracy of the nomogram in expanded diagnostic utilization to predict LUTO. METHODOLOGY: The validation of the nomogram for expanded diagnostic utilization was based on data from a prospective institutional antenatal clinic database between January 2020 and June 2022. Diagnostic accuracy indices were determined for confirmed postnatal diagnosis of LUTO or prune belly syndrome (PBS). Receiver operating characteristics (ROC) curves were generated to compare the area under the curve (AUC) of the nomogram versus KHS. RESULTS: Based on 84 male fetuses with antenatal ultrasound of moderate-severe hydronephrosis (PUV n = 15, PBS n = 4), the KHS had 26.3% (95%CI 9.1-51.2) sensitivity and 100% (95%CI 94.4%-100%) specificity, with 14 false-negatives. The nomogram showed a 84.2 (95%CI 60.4%-96.6%) sensitivity and 95.4 (95%CI 87.1%-99%) specificity with three false-positives. The nomogram also had a superior AUC compared to KHS (0.98 vs. 0.63). CONCLUSION: The nomogram can be used as a valuable tool to trigger further postnatal screening and provide individualized risk assessments to families during prenatal counseling.

The role of circumcision in preventing urinary tract infections in children with antenatal hydronephrosis: Systematic review and meta-analysis.

INTRODUCTION: Circumcision has been reported to reduce the risk of urinary tract infections (UTIs) in boys with antenatal hydronephrosis (HN). Our aim was to compare the incidence of UTIs in circumcised vs. uncircumcised boys with antenatal HN by conducting a systematic review and meta-analysis. STUDY DESIGN: A comprehensive search was performed until December 2022. Comparative studies were evaluated according to Cochrane collaboration recommendations. Assessed measures included: UTIs, continuous antibiotic prophylaxis (CAP) use, renal outcomes, and circumcision complications. Odds ratios (OR) and mean difference with 95% confidence interval (CI) were extrapolated from available data. Random-effects meta-analysis were performed. RESULTS: Twenty-three studies describing 9093 boys with antenatal HN were identified, including 4677 uncircumcised and 4416 circumcised boys. Overall effect estimates demonstrate that circumcised boys have significantly reduced odds of developing any UTI [OR 0.26, 95%CI 0.21, 0.32; p < 0.001]]. In addition, there a significantly reduced odds of developing UTI when circumcised and on CAP [OR 0.19, 95% CI 0.13, 0.30; p < 0.001]. When stratifying by etiology, circumcision reduced the odds of UTI in boys with isolated HN [OR 0.33, 95% CI 0.16, 0.68; p = 0.003], vesicoureteral reflux [OR 0.23, 95% CI 0.13, 0.42; P < 0.00001], or with posterior urethral valves [OR 0.29, 95% CI 0.13, 0.64; p = 0.002]. DISCUSSION: Circumcision reduces the incidence of UTIs in boys with antenatal HN. This review is limited by the varied definitions of UTIs and inconsistent reporting on HN etiology, renal outcomes, and circumcision complications. CONCLUSIONS: Circumcision should be considered in boys with antenatal HN to prevent the risk of developing UTI. Further research is warranted to individualize the prophylactic role of circumcision for patients with HN.

Implementation of a standardized clinical pathway in a dedicated posterior urethral valves clinic: short-term outcomes.

BACKGROUND: To determine if the implementation of a posterior urethral valves (PUV) clinic and standardized management pathway improves the short-term kidney outcomes of infants with PUV. METHODS: From 2016-2022, 50 consecutive patients were divided into groups after the implementation of the clinic (APUV, n = 29) and before (BPUV, n = 21) during a comparable timeframe. Assessed data included age at initial visit, timing and type of surgery, frequency of follow-up visits, medications, nadir creatinine, and development of CKD/kidney failure. Data are shown as median with interquartile range (IQR) and odds ratios (OR) with 95% confidence interval (CI). RESULTS: APUV had higher rates of prenatal diagnoses (12/29 vs. 1/21; p = 0.0037), earlier initial surgical intervention (8 days; IQR 0, 105 vs. 33 days; IQR 4, 603; p < 0.0001), and higher rates of primary diversions (10/29 vs. 0/21; p = 0.0028). Standardized management led to earlier initiation of alpha blockers (326 days; IQR 6, 860 vs. 991; IQR 149, 1634; p = 0.0019) and anticholinergics (57 days; IQR 3, 860 vs. 1283 days; IQR 477, 1718; p < 0.0001). Nadir creatinine was reached at earlier ages in APUV (105 days; IQR 2, 303 vs. 164 days; IQR 21, 447; p = 0.0192 BPUV). One patient progressed to CKD5 in APUV compared to CKD3, CKD5 and one transplant in BPUV. CONCLUSION: Implementing the PUV clinic with standardized treatment expedited postnatal management and resulted in a higher number of cases detected prenatally, a shift in primary treatment, younger ages at initial treatment, reduced time to nadir creatinine, and timely initiation of supportive medications. A higher resolution version of the Graphical abstract is available as Supplementary information.

Posterior urethral valves, pressure pop-offs, and kidney function: systematic review and meta-analysis.

PURPOSE: To determine the role of pressure pop-off mechanisms, including vesicoureteral reflux and renal dysplasia (VURD) syndrome, in determining long-term kidney outcomes in boys with posterior urethral valves (PUV). METHODS: A systematic search was performed in December 2022. Descriptive and comparative studies with a defined pressure pop-off group were included. Assessed outcomes included end-stage renal disease (ESRD), kidney insufficiency (defined as chronic kidney disease [CKD] stage 3 + or SCr > 1.5 mg/dL), and kidney function. Pooled proportions and relative risks (RR) with 95% confidence intervals (CI) were extrapolated from available data for quantitative synthesis. Random-effects meta-analyses were performed according to the study design and techniques. The risk of bias was assessed with the QUIPS tool and GRADE quality of evidence. The systematic review was prospectively registered on PROSPERO (CRD42022372352). RESULTS: A total of 15 studies describing 185 patients with a median follow-up of 6.8 years were included. By the last follow-up, overall effect estimates demonstrate the prevalence of CKD and ESRD to be 15.2% and 4.1%, respectively. There was no significant difference in the risk of ESRD in patients with pop-off compared to no pop-off patients [RR 0.34, 95%CI 0.12, 1.10; p = 0.07]. There was a significantly reduced risk for kidney insufficiency in boys with pop-off [RR 0.57, 95%CI 0.34, 0.97; p = 0.04], but this protective effect was not re-demonstrated after excluding studies with inadequate reporting of CKD outcomes [RR 0.63, 95%CI 0.36, 1.10; p = 0.10]. Included study quality was low, with 6 studies having moderate risk and 9 having a high risk of bias. CONCLUSIONS: Pop-off mechanisms may be associated with reducing the risk of kidney insufficiency, but current certainty in the evidence is low. Further research is warranted to investigate sources of heterogeneity and long-term sequelae in pressure pop-offs.

Assessing the Utility of Tamsulosin in Delaying Progression to Clean Intermittent Catheterization and End-stage Renal Disease in Patients With Posterior Urethral Valves: Are We Postponing the Inevitable?

OBJECTIVE: To assess whether tamsulosin may aid emptying of the lower urinary tract in posterior urethral valves patients, mitigating the likelihood of progressing to clean intermittent catheterization (CIC) or need for renal replacement therapy. METHODS: We reviewed a prospective institutional database containing posterior urethral valves patients treated between January 2000 and January 2022. After assessing baseline characteristics, Kaplan-Meier survival curves and log-rank tests were generated to assess differences in clinically significant outcomes (progression to CIC, dialysis, or kidney transplantation) between those prescribed tamsulosin and those who were not. RESULTS: A total of 179 patients were included. Fifty-nine patients received tamsulosin prior to initiation of CIC (group 1), and 120 did not (group 2). The baseline characteristics were similar between the two groups, except for anticholinergic use (tamsulosin group - 35/59 vs no tamsulosin - 32/120, P < .001). The median age at tamsulosin initiation was 26.0 months (IQR 15.5-48.6) and the median time from initiation of tamsulosin to progression to CIC was 52.6 months (IQR 10.1-69.3). Kaplan-Meier survival curves showed that patients on tamsulosin were less likely to progress to CIC (P = .021), however, there was no difference in progression to dialysis or kidney transplantation. A Cox-regression analysis controlling for baseline characteristics, including age, anticholinergic use, vesicoureteral reflux severity, and CKD stage at 1-year of life, showed a consistent effect of tamsulosin in delaying progression to CIC (HR 0.444 95%CI 0.218-0.902, P = .025). CONCLUSION: While tamsulosin may delay CIC, it does not appear to delay progression to end-stage renal disease. Additional studies exploring specific patient factors are required to determine the timing and subset who may benefit the most from tamsulosin.

Does VURD syndrome impact voiding efficiency in posterior urethral valves?

INTRODUCTION: There is debate regarding the effect of VURD syndrome, consisting of vesicoureteral reflux (VUR) and ipsilateral kidney dysplasia, on long-term outcomes in boys with posterior urethral valve (PUV). Here, we assessed whether VURD syndrome played a "protective" role on long-term bladder outcomes and voiding efficiency in boys with PUV. MATERIALS AND METHOD: A retrospective chart review was conducted for toilet-trained children with PUV managed at our institution between 2000 and 2022, only excluding cases without recorded uroflowmetry studies. Patients were stratified by VUR status and by the presence of VURD syndrome (high-grade VUR + ipsilateral kidney dysplasia). Outcomes included initial and final uroflowmetry parameters, and initiation of clean-intermittent catheterization (CIC). RESULTS: We identified a total of 101 patients who met study inclusion criteria, with an overall median follow-up of 114 months (IQR 67, 169). The median age of first and last uroflowmetry was 57 months (IQR 48, 82) and 120 months (IQR 89, 160), respectively. Patients with VURD syndrome had similar flow velocity, post-void residuals, and bladder voiding efficiency to other PUV patients at last follow-up uroflowmetry. On survival analysis, patients with VURD syndrome had no significant difference in risk of requiring CIC compared to patients without pop-offs (p = 0.06). DISCUSSION: Like more contemporary studies on pressure pop-offs, we show that this population is not at higher risk of poorer voiding and intermittent catheterization than others. VURD syndrome does not confer protection against poorer bladder function. Instead, our study suggests an independent association between kidney dysplasia and bladder outcomes which requires further attention. CONCLUSIONS: Among boys with PUV, VURD syndrome was not associated with significantly different uroflowmetry findings or rates of CIC by last follow-up.

Primary ablation versus urinary diversion in posterior urethral valve: Systematic review and meta-analysis.

PURPOSE: To determine differences in long-term kidney and bladder outcomes in boys with posterior urethral valves (PUV) managed by a primary valve ablation or primary urinary diversion. MATERIALS AND METHODS: A systematic search was performed in March 2021. Comparative studies were evaluated according to Cochrane collaboration recommendations. Assessed measures included kidney outcomes (chronic kidney disease, end-stage renal disease, kidney function) and bladder outcomes. Odds ratios (OR) and mean difference (MD) with 95% confidence interval (CI) were extrapolated from available data for quantitative synthesis. Random-effects meta-analysis and meta-regression were performed according to study design, and potential covariates were assessed with subgroup analysis. The systematic review was prospectively registered on PROSPERO (CRD42021243967). RESULTS: Thirty unique studies describing 1547 boys with PUV were included in this synthesis. Overall effect estimates demonstrate that patients undergoing primary diversion have significantly increased odds of developing renal insufficiency [OR 0.60, 95% CI 0.44, 0.80; p < 0.001]. However, when adjusting for baseline kidney function between intervention groups, there was no significant difference in long term kidney outcomes [p = 0.09, 0.35], or the development of bladder dysfunction or requiring clean-intermittent catheterization with primary ablation rather than diversion [OR 0.89, 95% CI 0.49, 1.59; p = 0.68]. CONCLUSIONS: Current low-quality evidence suggests that medium-term kidney outcomes in children are similar between primary ablation and primary diversion after adjusting for baseline kidney function, while bladder outcomes are highly heterogenous. Further research with covariate control is warranted to investigate sources of heterogeneity. LEVEL OF EVIDENCE: Level III.

The effect of primary urinary diversion on kidney function in posterior urethral valve: A matched comparison.

OBJECTIVE: To determine long-term kidney outcomes in boys with posterior urethral valve (PUV) undergoing either primary valve ablation or urinary diversion with matched baseline kidney function. METHODS: After retrospective review of patients managed for PUV at our institution, propensity score matched analysis was conducted using nadir serum creatinine with logistic regression analysis. Nearest neighbor matching was used to allocate boys to primary urinary diversion and primary ablation groups. Primary outcomes included kidney function by creatinine or estimated glomerular filtration rate, chronic kidney disease, and end-stage renal disease. Comparative statistics by odds ratio (OR) and hazard ratios on survival analysis were calculated. RESULTS: A total of 21 boys undergoing primary diversion were matched with 42 boys undergoing ablation using nadir serum creatinine and follow-up time with a median follow-up of 4.8 years. After matching, there was no significant difference in last follow-up kidney function by creatinine (P = .99) or estimated glomerular filtration rate (P = .98). Primary diversion was not associated with increased likelihood of developing chronic kidney disease stage 3 (OR 1.33; P = .31) or end-stage renal disease (OR 1.88; P = .35 and hazard ratios 1.85; P = .30) compared to primary ablation. CONCLUSIONS: Our propensity matched study suggests that long-term kidney function and kidney outcomes are similar between primary ablation and primary diversion after adjusting for baseline kidney function in boys with PUV.

Use of timed alarm device for pediatric daytime urinary incontinence Meta-analysis of comparative studies.

INTRODUCTION: This meta-analysis aimed to determine the comparative effectiveness of timed alarm device-assisted urotherapy vs. standard urotherapy alone in managing pediatric daytime urinary incontinence (pDUI). METHODS: A systematic literature search was performed in December 2021, with an update search in July 2022. Comparative studies assessing the pDUI treatment effectiveness of timed alarm device-assisted urotherapy vs. urotherapy alone were identified and evaluated according to Cochrane collaboration recommendations. The assessed outcome includes pDUI complete response and adherence rates. Relative risk (RR ) with 95% confidence intervals (CI) was extrapolated. A random-effects model was used to pool effect estimates. Heterogeneity was assessed with sensitivity and subgroup analysis performed according to study design and comparative group characteristics. GRADE criteria were used to assess evidence certainty. (PROSPEROCRD 42022299173). RESULTS: Four studies (three randomized controlled trials [RCTs] and one retrospective cohort) with 635 cases were included. The pooled effect estimates of pDUI complete response showed no differences between intervention groups (RR 1.20, 95% CI 0.81, 1.76). Pooled effect estimates for treatment adherence were generated from two studies, which showed significantly better adherence for the timed-alarm device group (RR 2.97, 95% CI 1.46, 6.06). Significant interstudy heterogeneity was noted; the source is likely from the study design and comparator device characteristics. The quality of evidence was assessed to be of very low certainty. CONCLUSIONS: Based on very low certainty evidence, timed alarm device-assisted urotherapy does not seem to have the advantage of complete treatment response over standard urotherapy alone in managing pDUI; however, a timed-alarm device is likely able to improve urotherapy treatment adherence.

Scoping review of neurogenic bladder patient-reported readiness and experience following care in a transitional urology clinic.

OBJECTIVE: To generate a scoping review that summarizes thematically on all reported patient perceptions on readiness and experiences during transitional urologic care for patients with neurogenic bladder and or congenital genitourinary conditions that require continuity of care into adulthood. METHODS: A systematic literature search was performed in October 2021. Records were screened and identified for studies relevant to reported readiness and experience in urologic transitional care among patients needing life-long urologic care. The methodological quality of the cross-sectional studies was assessed using AXIS. The included studies were clustered according to patient readiness in transition and patient experience-satisfaction in the urologic transition process. This scoping review was part of a systematic review registered on PROSPERO CRD42022306229 and was conducted in compliance with the PRISMA extension for scoping reviews. RESULTS: A total of 12 articles were included that assessed patients with neurogenic bladder that reported either readiness or patient experience following the transitional care process. The patient readiness was assessed in six studies, determined using the TRAQ score with a range of 3-4/5. Older age, high health literacy, and parental or families' transition process awareness were associated with readiness. Generally, patients experience better satisfaction with pediatric care than with adult care facilities. Most patients felt that sexuality and fertility were not adequately tackled during the transition. The reported barriers to successful transition were patient, provider, and system factors, including lack of insurance coverage/financial management, patient preference, long-term bond with the pediatric providers, and communication by the adult provider. Based on AXIS, all of the studies identified for this scoping review did not determine the sample size, and most of the studies did not categorize the responders, which could introduce bias to the interpretation of their results. CONCLUSION: This scoping review summarizes the readiness and experience of neurogenic bladder patients who underwent the urologic transitional process. Overall, understanding the patient, provider, and system factors associated with better readiness and enhancing the patient experience will ensure a better transition process.

Bladder Training Video versus Standard Urotherapy for Bladder and Bowel Dysfunction: A Noninferiority Randomized, Controlled Trial.

PURPOSE: We evaluated whether an animated bladder training video was as effective as standard individual urotherapy in improving bladder/bowel symptoms. MATERIALS AND METHODS: Patients 5 to 10 years old who scored greater than 11 on the bladder/bowel Vancouver questionnaire were included in a noninferiority randomized, controlled trial. Children with vesicoureteral reflux, neuropathic bladder, learning disabilities, recent urotherapy or primary nocturnal enuresis were excluded from analysis. Patients were randomly assigned to receive standard urotherapy or watch a bladder training video in clinic using centralized blocked randomization schemes. Bladder/bowel symptoms were evaluated at baseline and 3-month followup by intent to treat analysis. A sample size of 150 patients ensured a 3.5 difference in mean symptomology scores between the groups, which was accepted as the noninferiority margin. RESULTS: Of 539 screened patients 173 (37%) were eligible for study and 150 enrolled. A total of 143 patients (95%) completed the trial, 5 (4%) were lost to followup and 2 (1%) withdrew. Baseline characteristics were similar between the groups. Baseline mean ± SD symptomology scores were 19.9 ± 5.5 for the bladder training video and 19.7 ± 6.0 for standard urotherapy. At 3 months the mean symptomology scores for the bladder training video and standard urotherapy were reduced to 14.4 ± 6.5 and 13.8 ± 6.0, respectively (p = 0.54). The mean difference was 0.6 (95% CI -1.4-2.6). The upper 95% CI limit of 2.6 did not exceed the preset 3.5 noninferiority margin. CONCLUSIONS: The bladder training video was not inferior to standard urotherapy in reducing bladder/bowel symptoms in children 5 to 10 years old. The video allows families to have free access to independently review bladder training concepts as often as necessary.

A pilot randomized controlled trial evaluating the effectiveness of group vs individual urotherapy in decreasing symptoms associated with bladder-bowel dysfunction.

PURPOSE: We determined the feasibility of a definitive trial comparing the effectiveness of group vs individual urotherapy for children with bladder-bowel dysfunction. MATERIALS AND METHODS: Children 6 to 10 years old with bladder-bowel dysfunction were recruited during the course of 1 year. Feasibility data on screening, eligibility, recruitment and protocol compliance rates were collected. Patients with high grade hydronephrosis, vesicoureteral reflux or learning disabilities and those who had previously undergone urotherapy were excluded. Patients were randomized to 1-hour group urotherapy or 15-minute individual urotherapy. Symptoms and quality of life were measured using the Vancouver Nonneurogenic Lower Urinary Tract Dysfunction/Dysfunctional Elimination Syndrome Questionnaire and the Pediatric Incontinence Questionnaire at baseline and at 3 to 6 months of followup. Within/between group comparisons were conducted using t-tests. RESULTS: Of 455 screened children 79 were eligible and 60 were recruited to participate. A total of 24 patients randomized to group urotherapy and 25 randomized to individual urotherapy completed the pilot trial (6 undergoing group and 5 undergoing individual urotherapy withdrew from the study). Symptomology scores between group and individual urotherapy were not different at followup (mean ± SD 14.7 ± 7.9 vs 13.4 ± 6.3, p = 0.54, 95% CI -5.4-2.8). Quality of life scores between patients undergoing group and individual urotherapy at baseline differed (mean ± SD 21.1 ± 10.8 vs 31.0 ± 14.3, p < 0.01, 95% CI 2.7-7.3) but became similar at followup (21.0 ± 14.2 vs 20.1 ± 15.3, p = 0.84, 95% CI -9.4-7.6). Within group analyses demonstrated improvement in symptomology from baseline to followup in patients undergoing group (mean ± SD 3.6 ± 7.6, p = 0.03, 95% CI 0.4-6.8) and individual urotherapy (6.0 ± 5.4, p < 0.01, 95% CI 3.8-8.3). Within group quality of life analyses revealed improvement in Pediatric Incontinence Questionnaire scores from baseline to followup in patients undergoing individual urotherapy (p < 0.01, 95% CI 5.0-16.9) only. CONCLUSIONS: Urotherapy, regardless of modality, effectively improved bladder-bowel dysfunction symptoms. A definitive randomized controlled trial is feasible, considering that a high recruitment rate (76%) for this population has been established.