Though most children with classic bladder exstrophy (CBE) are born with normal functioning kidneys, renal decompensation into adulthood has been observed.^1-3 Little is known about the incidence and development of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) in people with CBE who have undergone repair. We recently performed a retrospective review of 201 people who underwent CBE repair over a span of 36 years (1980-2016) across 5 tertiary care centers participating in PUMA (Pediatric Urology Midwest Alliance).⁴ The primary outcome was the incidence of ESKD, defined as needing peritoneal dialysis, hemodialysis, or renal transplantation. The secondary outcome was the development of stage 3 or higher CKD based on creatinine-based estimated glomerular filtration rates.

Figure. End-stage kidney disease among people with classic bladder exstrophy after primary bladder closure.

From the previously described cohort of 216 people with CBE, 201 had ESKD data available for inclusion in the study.⁵ Most participants were male (63%) and were followed to a median age of 18.8 years (IQR 11.3-25.3). Hypothesizing that primary closure of CBE may increase bladder outlet resistance and predispose these individuals to later CKD, we analyzed outcomes in 2 groups: (1) those who underwent primary urinary diversion, continent or incontinent, and (2) those who underwent primary bladder closure. Of the 4 people who underwent primary diversion, everyone remained diverted at a median follow-up of 20.1 years of age. None of the 4 developed ESKD. One woman developed stage 3 CKD at 33 years old. She previously underwent cystectomy and continent urinary reservoir at 1 year of age.

In the group of 197 people with CBE who underwent primary closure, 12 individuals (6%) were ultimately diverted, 108 (55%) were ultimately augmented, and 77 (39%) had neither. Three people (1.5%) with primary closure developed ESKD at a median age of 23.4 years. They all had prior Young-Dees-Leadbetter bladder neck repairs in the first 4 years of life (2 were subsequently revised and underwent a bladder neck closure), bladder augmentation, bilateral ureteral reimplantations, and creation of urinary catheterizable channels at age 3 to 5 years. A survival analysis was performed revealing a risk of ESKD of 0% at 10 years, 1% at 20 years, and 5% at 30 years (Figure). This was significantly higher than the risk of ESKD in the general population for 21 year olds of 0.003% (P < .001). Eight individuals (6%) of 141 people in this group who had renal function data available developed stage 3 or higher CKD. Stratifying by age, no patients younger than 10 years had stage 3 or higher CKD. One adolescent (4%) and 8 adults (8%) had stage 3 or higher CKD (Table). There was no statistically significant difference in the prevalence of CKD between these age groups or between centers. The study lacked statistical power for further risk factor analysis.

Table. Prevalence of Chronic Kidney Disease Among Children, Adolescents, and Adults With Classic Bladder Exstrophy Managed With Primary Bladder Closure Who Had Estimated Glomerular Filtration Rate Data Available

Previous studies looking at renal outcomes in CBE have not adjusted for differential follow-up time. Kanobolo et al reported that 2% of 36 people developed stage 3 or higher CKD at a mean age of 9 years old following complete primary repair of bladder exstrophy. They did not detect a significant difference in CKD between sexes.⁶ Joshi et al reported that 3% of 72 people developed stage 3 or higher at a median follow-up of 4 years after complete primary repair of bladder exstrophy. They specifically looked at continence status, defined into various categories of dry intervals, as a risk factor for CKD and did not find any association with renal functional outcomes.⁷

The risk of ESKD in people with CBE who underwent primary closure appears similar to rates seen in people with myelomeningocele (MMC). Prior research from our institution evaluating 1029 people with MMC for a median follow-up time of 17 years noted a risk of ESKD of 0.2% at 20 years and 2% at 30 years.⁸ In both populations, rates of ESKD appear to be over 100-fold higher than the general population.

These studies highlight the importance of continued multi-institutional collaborations, such as PUMA and others, given the low overall rate of ESKD and CKD in an already rare disease. At least in the realm of MMC, there is historical precedent leading to continued concern about minimizing risks of ESKD and mortality related to ESKD, both of which have been significantly reduced in the modern medical era. Renal function preservation plays a critical role in MMC care. Our results suggest it should play a similarly important role in the care of people with CBE.

Our study presents the first age-based estimates of renal function outcomes in CBE. We hope it serves as a starting point for improvement. When it comes to CBE, it is unclear if renal deterioration is a result of increasing bladder outlet resistance and if it varies with different reconstructive approaches. The limited data we present indicate that neither primary closure group nor diverted group may be spared CKD. Future multi-institutional studies are needed to continue to evaluate renal preservation strategies in CBE, with an emphasis on standardized, comprehensive, and reliable long-term data.