Infantile versus childhood posterior urethral valve diagnosis: management patterns and clinical outcomes at opposite ends of the spectrum.

BACKGROUND: Management patterns and outcomes are poorly defined in cases of late PUV diagnosis. OBJECTIVE: To compare post-ablation management and clinical outcomes of patients with infantile (<1 year) versus childhood (>5 year) PUV diagnosis to gain insight into the pathologies at opposite ends of the PUV spectrum. STUDY DESIGN: A multicenter retrospective cohort study was conducted using the TriNetX research network between 2006 and 2022. TriNetX synthesizes insurance claims and electronic medical record data for over 110 million patients from 92 healthcare organizations. We defined two cohorts: 1) The <1 year arm had an index diagnosis of PUV and cystoscopy with valve ablation within 1 year of life, 2) the >5 year arm had an index diagnosis of PUV and valve ablation after age 5. We report rates and time-to-first use of antispasmodics, alpha-blockers, CIC, bladder botox, enterocystoplasty or Mitrofanoff or secondary cutaneous vesicostomy, and CKD. RESULTS: We identified 569 patients (323 <1 year; 246 >5 year). Median age at diagnosis was 1 month (median follow-up 8 years) and 9 years (median follow-up 10 years) for the <1 year and >5 year cohorts, respectively. Following ablation, both arms were primarily managed with antispasmodics, with no difference between groups. The >5 year arm was significantly more likely to receive alpha-blockers or bladder botox. The <1 year arm was significantly more likely to be started on CIC, undergo enterocystoplasty, Mitrofanoff or secondary cutaneous vesicostomy, or renal transplantation. The <1 year arm had significantly higher rates and shorter time-to-progression to all stages of CKD. DISCUSSION: Despite higher utilization of conservative strategies among patients with a late PUV diagnosis, these patients had superior renal outcomes and low rates of progression to invasive treatments. Limitations include potential inaccuracies in medical coding as well as variations in thresholds to initiate CIC, perform surgical reconstruction, or proceed with renal transplantation at participating centers. CONCLUSIONS: These findings provide evidence that a late PUV diagnosis reflects an overall milder disease process.

Role of progressive urethral dilation and primary valve ablation in the long-term renal outcomes of small, preterm infants with posterior urethral valve.

INTRODUCTION: PUV patients managed with primary vesicostomy instead of primary valve ablation (PVA) historically are preterm, low-birth-weight (LBW) infants with inadequate urethral size. We previously described progressive urethral dilation (PUD) as an effective method of enhancing the likelihood of PVA in these infants, allowing equal access to PVA as an initial management method. OBJECTIVE: We aim to characterize renal outcomes in patients managed with PUD + PVA and compare this to outcomes with PVA alone. We also re-examine the effect of LBW and gestational age on renal outcomes in PUV with a cohort treated uniformly by PVA. METHODS: We performed retrospective review of 78 neonates with PUV treated with PVA prior to 10 weeks of age with >1 year of follow up. Before valve ablation, boys either underwent PUD (serial upsizing of a smaller bore urethral catheter to an 8Fr catheter; PUD + PVA) or non-dilation (smaller bore catheter was maintained; PVA-only). PUD + PVA versus PVA-only was compared using chi-square and t-test. Logistic regression was performed to assess the effect of PUD, preterm (<37 weeks), LBW (<2.5 kg), and other predictors on the final outcomes of CKD3+ and ESRD. RESULTS: 31 of 78 patients underwent PUD + PVA. Mean follow up was 5.2 years (SD 3.4), with no significant difference between PUD + PVA and PVA-only. The PUD + PVA group included significantly lower gestational age infants with lower birth weight and ablation weight. There was no significant effect of PUD on final CKD3+ or ESRD outcome on univariable or multivariable analysis. When adjusted for other variables, only Cr nadir >0.5 remained an independent predictor of CKD3+ (OR 41.2; p < 0.001) and ESRD (OR 18.9; p = 0.015). DISCUSSION: We previously demonstrated that PUD is an effective means to achieve PVA in small neonates who might otherwise require vesicostomy. The data herein demonstrates no significant effect of PUD on renal outcomes. In this unique cohort of newborns treated with PVA, only creatinine nadir and not gestational age or an independent predictor of outcomes. CONCLUSION: In small preterm infants who would have been excluded from PVA due to limited urethral size, PUD + PVA confers the same renal outcomes as PVA alone in larger infants. This novel data will assist in the risk-benefit analysis of using PUD before PVA in newborns diagnosed with PUV. When primary intervention is uniformly PVA, preterm birth and LBW are not independent predictors of renal outcomes.

Posterior urethral morphology on initial voiding cystourethrogram correlates to early renal outcomes in infants with posterior urethral valves.

INTRODUCTION: Posterior urethral valves (PUV) is a leading cause of chronic renal failure in childhood. Bladder and posterior urethral deformity in infants with PUV are highly variable on initial voiding cystourethrogram (VCUG). Some types of deformity may be more important than others in determining the severity of the condition. Identification of specific VCUG features may allow for a simple, early screening assessment for patients. OBJECTIVE: Determine whether morphologic features on the initial VCUG correlate to renal outcomes as measured by the creatinine nadir in the first year after ablation. METHODS: Children with PUV treated by primary valve ablation before 12 months old and followed >1 year were identified. Initial diagnostic VCUG was evaluated for the bladder height to width ratio (HW-B), posterior urethral height to width ratio (HW-PU), and posterior-anterior urethral ratio (PA-UR). A trabeculation grade was assigned by three pediatric urologists, and reflux was noted. Univariable analyses with chi-square and t-test were used to compare bladder and posterior urethral morphology factors among those who obtained a creatinine nadir <0.8 or ≥0.8 mg/dL in the first year after ablation. Linear regression was performed to correlate morphology values with true creatinine nadir. RESULTS: A total of 120 boys were ablated at mean age of 40.5 days (range 0-342) and followed for 5.9 years (± 3.85). Among these, 21 (17.5%) had a creatinine nadir ≥0.8 mg/dL. Mean overall HW-B and mean PA-UR were not significantly different between those with creatinine nadir <0.8 versus ≥0.8 mg/dL. Bladder trabeculation grade was not associated with creatinine nadir. For the entire cohort, only the difference in HW-PU was statistically significant between creatinine nadir groups with a much higher ratio among those with a nadir ≥0.8 (p < 0.001). Linear regression demonstrated a significant positive correlation between the HW-PU and creatinine nadir (R 2 = 0.097, p = 0.002). The presence of bilateral reflux is significantly associated with creatinine nadir ≥0.8 mg/dL (p = 0.001). DISCUSSION: We investigate for the first time the association of morphology features on the initial VCUG with renal outcome in PUV patients. Posterior urethral deformity as quantified by a higher HW-PU ratio is significantly correlated with a higher creatinine nadir, whereas measured bladder morphology metrics are not. HW-PU may be an indirect measure of the severity of obstruction in posterior urethral valves. CONCLUSION: The HW-PU appears to be a meaningful early morphologic metric for renal outcome.

Predicting childhood chronic kidney disease severity in infants with posterior urethral valve: a critical analysis of creatinine values in the first year of life.

BACKGROUND: Posterior urethral valve (PUV) is a leading cause of chronic kidney failure in children. Studies have shown that a creatinine nadir above historical cutoff values of 0.8 or 1.0 mg/dL correlates with worse kidney outcomes. The ability to use nadir creatinine more discriminately as a test of kidney outcomes is otherwise limited. METHODS: We performed a retrospective review of 102 infants treated with primary valve ablation prior to 1 year of age. Patient factors including creatinine at presentation (Cr-P), nadir within 6 weeks after ablation (Cr-6 W), and nadir within 1 year after ablation (Cr-1Y) were assessed as predictors of final chronic kidney disease (CKD) severity. An optimal threshold for four CKD levels was defined in incremental fashion using binary outcome with receiver operating characteristic (ROC). Multivariable logistic regression models compared Cr-P, Cr-6 W, and Cr-1Y while adjusting for patient factors. RESULTS: Boys were ablated at mean age of 36.3 days and followed for 6.6 years (± 3.7). When compared to other demographics, only creatinine remained independently predictive of CKD outcomes on multivariable analysis. ROC analysis demonstrated excellent diagnostic accuracy for Cr-6 W and Cr-1Y (p < 0.001) and acceptable accuracy for Cr-P (p < 0.005). Using the Cr-6 W and Cr-1Y models, high sensitivity and specificity creatinine nadir cutoffs were determined to predict each CKD outcome. CONCLUSIONS: The severity of childhood CKD can be predicted with high accuracy using the creatinine nadir within 6 weeks of ablation. The cutoff values described can be incorporated into a clinical setting for patient counseling and individual risk stratification.

Role of a Preoperative Catheter Regimen in Achieving Early Primary Endoscopic Valve Ablation in Neonates with Posterior Urethral Valves.

PURPOSE: Primary valve ablation is preferred to vesicostomy in the initial management of posterior urethral valves. However, some neonates have a prohibitively small urethra. We describe our experience with a preoperative urethral catheter regimen to enhance the likelihood of neonatal valve ablation. MATERIALS AND METHODS: We performed a retrospective review of 126 neonates with posterior urethral valves treated between 2003 and 2019 with valve ablation prior to 10 weeks of age. The preoperative indwelling catheter either was gradually upsized to an 8Fr (progressive urethral dilation), was not upsized (nondilated) or was initially larger bore (8Fr only). The primary outcome was the ability to perform primary ablation by neonatal resectoscope. The secondary objective was to establish the parameters for considering progressive urethral dilation as well as its associated risks. RESULTS: Overall 97% could be ablated. The progressive urethral dilation group had the lowest mean weight (p <0.001). Only a larger catheter at the time of ablation was significantly associated with feasible ablation (p <0.001) and not urethral dilation, the infant's weight or his gestational age. Progressive urethral dilation was associated with a longer duration of catheterization as well as double the rate of febrile urinary tract infections (8.5%) over the nondilated group (3.6%). CONCLUSIONS: A much higher rate of primary ablation is feasible (97%) than previously reported (82%). More important than the infant's weight is whether a 6Fr to 8Fr catheter is in place at ablation. If an initial 6Fr to 8Fr catheter cannot be placed, urethral dilation to 8Fr should be performed before attempting ablation. This is both a technique and preoperative assessment that is useful for operative planning.

A Review of Mullerian Anomalies and Their Urologic Associations.

Structural anomalies of the female reproductive tract, known as Mullerian anomalies, can occur in isolation or in association with anomalies of other organ systems. Due to shared embryology, the most common association in up to 40% of patients is with renal, ureteral, and bladder anomalies. Affected girls can have a wide range of genitourinary symptoms with urologists playing an integral role in their diagnosis and treatment. To facilitate the recognition and management of these conditions, we provide a review of Mullerian anomalies including the embryology, classifications, syndromes, evaluation, and treatments with attention to their urologic applicability.

Predicting Breakthrough Urinary Tract Infection: Comparative Analysis of Vesicoureteral Reflux Index, Reflux Grade and Ureteral Diameter Ratio.

PURPOSE: The vesicoureteral reflux index is a simple, validated tool for predicting resolution of reflux. Along with likelihood of spontaneous resolution identification of children at risk for febrile urinary tract infection impacts management. We evaluated the usefulness of the vesicoureteral reflux index as a predictive factor for breakthrough febrile urinary tract infection compared to reflux grade and distal ureteral diameter ratio. MATERIALS AND METHODS: Children with primary vesicoureteral reflux and detailed voiding cystourethrogram data were identified. A 1 to 6-point index was assigned, and ureteral diameter ratio was computed by measuring largest ureteral diameter within the pelvis and dividing by the distance between L1 to L3 vertebral bodies. Random forest modeling and logistic multivariable regression were employed to estimate the predictive ability of grade, ureteral diameter ratio and vesicoureteral reflux index with regard to breakthrough febrile urinary tract infection. RESULTS: We analyzed 94 girls and 45 boys with a mean±SD age of 5.4±4.7 months at diagnosis. Mean±SD length of followup was 32.1±24.5 months. A total of 13 children (9.4%) experienced breakthrough febrile urinary tract infection. On univariate analysis ureteral diameter ratio (p=0.01) and vesicoureteral reflux index (p=0.0005) were associated with breakthrough urinary tract infection, while grade (p=0.09) did not reach significance. Area under the curve was generated as a measure of accuracy for each variable and was 0.77 for the vesicoureteral reflux index, 0.71 for ureteral diameter ratio and 0.68 for grade, indicating superiority of the vesicoureteral reflux index for predicting breakthrough febrile urinary tract infection. CONCLUSIONS: Children with higher vesicoureteral reflux index are at increased risk for breakthrough febrile urinary tract infection independent of reflux grade. The vesicoureteral reflux index provides valuable prognostic information about infection risk, facilitating improved clinical decision making.

Fate of Pediatric Renal Angiomyolipoma During mTOR Inhibitor Treatment in Tuberous Sclerosis Complex.

OBJECTIVE: To evaluate the clinical and radiographic follow-up of renal angiomyolipoma (AML) in pediatric patients with tuberous sclerosis complex (TSC) on mTOR inhibitors. METHODS: We performed retrospective chart review of children who were diagnosed with TSC between 2000 and 2019 and prescribed everolimus at age ≤18 years. Treatment assessment was performed in patients who were medically-compliant by serum drug trough levels and who had at least a baseline and one subsequent renal imaging study. RESULTS: Nineteen patients were analyzed. Average age of everolimus initiation was 9 years, and indication was neurologic in 17 (90%). Fourteen patients (73.6%) had AML with average size of 1.9 (0.4-5) cm. Medication was discontinued due to side effects in 3 (16%) patients. Treatment assessment was analyzed for 15 patients with median medication exposure 5.1 (0.8-8.5) years. Among 13 with AML, the dominant lesion decreased in size in 9 (69%) and stayed stable in 4 (31%). Greatest absolute size decrease was seen for lesions ≥2 cm. No new AML lesions formed during treatment. CONCLUSION: Although not currently approved for this indication, everolimus appears to be well-tolerated with similar efficacy for pediatric AML as in adult AML. Use may be most warranted in children with AML ≥2 cm.

Revisiting the success rate of one-stage Fowler-Stephens orchiopexy with postoperative Doppler ultrasound and long-term follow-up: a 15-year single-surgeon experience.

INTRODUCTION: The optimal management of a high undescended testicle (UDT) remains debated. When tethering is due to shortened spermatic vessels, a one-stage or two-stage Fowler-Stephens Orchiopexy (FSO) can be performed. Published series suggest a higher success rate with a two-stage FSO, though its superiority has not been ascertained. The authors examine patient and surgical factors associated with success of one-stage FSO and compare our outcomes with the established literature. METHODS: We retrospectively reviewed the charts of 43 boys who underwent one-stage FSO for 45 testes from 2003 to 2018 by a single surgeon at our institution. Patient factors, surgical approach, and postoperative results were reviewed. Radiographic success was a testis with intact vascular flow or normal echotexture on scrotal ultrasound. Clinical success was a non-atrophic, intrascrotal testis at postoperative follow-up. Radiographic and clinical success was compared. Data analysis was performed with Fisher's exact test and t-test for categorical and continuous variables respectively. RESULTS: Follow-up (mean 29 months; 0.5 months-14.5 years) was available for 40 patients (42 testes; 21 bilateral, 21 unilateral). Average age at surgery was 21.8 months (4 months-10.4 years). Associated conditions were seen in 14 patients. Twenty-nine patients had postoperative scrotal Doppler ultrasound with radiographic success in 25/29 (86.2%). Overall clinical success was 34/42 (81%) with 4 (9.5%) each of atrophy and ascent. A second surgery to address ascent in four patients allowed correction in three for a success rate of 88%. Radiographic and clinical success was significantly associated (P = 0.01). Clinical success was also significantly associated with inguinal rather than laparoscopic testis mobilization (P = 0.03) but not to patient's age, associated conditions, unilaterality/bilaterality, or pre-operative hypoplasia or location. Greater than 3 years of follow-up was available in 11 (26.2%) cases, of which seven had successful results. All adverse outcomes occurred within 8 months after surgery. Success was otherwise durable. CONCLUSION: This is the largest series of one-stage FSO to date. The success rate of one-stage FSO in this series matches that published in the literature for two-stage FSO; equal success is achieved with fewer surgeries. Postoperative Doppler ultrasound demonstrating intact vascular flow or normal testis echotexture is significantly associated with clinical success and highlights the utility of postoperative ultrasound in patients with an equivocal exam.

Robot-Assisted Laparoscopic Heineke-Mikulicz Ureteroplasty for Congenital Mid-Ureteral Stricture and Ipsilateral Distal Megaureter Repair in a Child.

Background: Congenital mid-ureteral stricture (CMUS) is a rare diagnosis almost exclusively repaired with ureteroureterostomy in infancy or early childhood. Case Report: We describe a unique case of a 2-year-old child with both a CMUS and ipsilateral obstructed megaureter, which was addressed in a single operative setting using a robotic Heineke-Mikulicz nondismembered ureteroplasty for the CMUS and a dismembered tapered extravesical ureteral reimplant for the obstructed megaureter. Conclusion: Compared with ureteroureterostomy, a nondismembered ureteroplasty for CMUS minimizes the risk of ureteral vascular compromise and can be particularly beneficial in cases where the affected ureter requires additional reconstruction. Use of robot-assisted technology for complex ureteral reconstruction in the pediatric population is safe and effective.

Management of vesicoureteral reflux in neurogenic bladder.

Vesicoureteral reflux (VUR) is a significant risk factor for pyelonephritis and renal scarring. VUR can occur through a defective ureterovesical junction (UVJ) or an overwhelmed normal UVJ mechanism such as in bladder dysfunction of congenital, acquired, or behavioral etiology. There are numerous causes for the development of a neurogenic bladder from spinal dysraphisms to spinal cord trauma and even centrally based abnormalities in children with apparently normal motor function (inappropriately termed nonneurogenic neurogenic bladder). The foundation of managing reflux in these neurogenic bladders is to maintain low bladder pressures which will commonly mean that compliance will be normal as well. There have been several publications that have shown that if bladder pressures are lowered simply with clean intermittent catheterization and medications that the reflux can resolve spontaneously. Alternatively, the patients that are in need of bladder augmentation can have spontaneous resolution of their reflux with the resulting increase in capacity. Surgical intervention is called for when bladder capacity is adequate and the reflux persists or if it is part of a larger operation to increase capacity and to manage outlet resistance. In some instances, reimplantation is necessary because the ureters interfere with the bladder neck procedure. Aside from open and robotic surgical intervention the use of endoscopic injectable agents is beginning to become more popular especially when combined with intravesical botulinum toxin A injections. Great strides are being made in the management of patients with neurogenic bladders and we are seeing more choices for the urologist to be able to manage these patients.

Distinguishing pediatric and adolescent renal cell carcinoma from other renal malignancies.

PURPOSE: Renal cell carcinoma (RCC) represents a small proportion of renal malignancies early in life. Distinguishing RCC from other malignancies is important as treatment strategies may differ. We analyze the Surveillance Epidemiology, and End Results (SEER) database to identify predictive factors of RCC in the pediatric population with renal tumors. METHODS: We queried SEER to identify patients from ages 0 to 19 diagnosed with a renal malignancy between 1973 and 2013. Cases were sorted using histology and site codes. Age-adjusted standardized incidence rates (SIR) were calculated. We compared differences in characteristics between cancer types. A logistic regression model and a nomogram were created to identify predictors of RCC. RESULTS: A total of 3,670 patients were identified, of which 281 (7.7%) were diagnosed with RCC. The SIR of RCC increased with age. After age 12, RCC was found in >50% of all newly diagnosed cases. On multivariate analysis, RCC was associated with smaller tumor size (P < 0.001), increasing age (P < 0.001), black race (P < 0.001), and localized stage (P < 0.001). The nomogram predicted RCC pathology with a concordance index of 0.965. CONCLUSIONS: RCC in childhood and adolescence is relatively uncommon; however, it accounts for >50% of renal malignancies after age 12. For every year of increasing age, the odds of having an RCC diagnosis are increased by 50%. The odds of a renal tumor being RCC are increased in black children, those with localized disease, and those with smaller tumors. In these specific populations, RCC should be favored in the differential diagnosis of the renal mass.