Long-Term Kidney Outcomes in Children with Posterior Urethral Valves: A Population-Based Cohort Study

Abstract

Key Points:

1. Among 727 children with posterior urethral valves, 32% had major adverse kidney events (death, kidney failure, or CKD) over a median of 14.2-year follow-up.

2. Children with posterior urethral valves were at substantially higher risks of kidney failure, CKD, and hypertension than the general population.

3. This justifies close kidney health surveillance among children with posterior urethral valves and optimized transitions to adult urologic care.

Background: Posterior urethral valves represent the most common cause of lower urinary tract obstruction in male infants (approximately 1/4000 live births). Long-term kidney outcomes of posterior urethral valves remain uncertain. We aimed to determine the time-varying risk of major adverse kidney events (MAKE) following children with posterior urethral valves into adulthood.

Methods: A population-based retrospective cohort study of all male children (<2 years) diagnosed with posterior urethral valves between 1991 and 2021 in Ontario, Canada. Comparator cohorts were (1) male general population and (2) male children with pyeloplasty (both <2 years). The primary outcome was MAKE (death, long-term KRT [dialysis or kidney transplant], or CKD). Time to MAKE was analyzed using multivariable-adjusted Cox proportional hazards models. We censored for provincial emigration or administrative censoring (March 31, 2022).

Results: We included 727 children with posterior urethral valves, 855 pyeloplasty comparators, and 1,013,052 general population comparators. The median follow-up time was 16.6 years (Q1–3, 8.6–24.5) overall. Throughout follow-up, 32% of children with posterior urethral valves developed MAKE versus 1% of the general population and 6% of pyeloplasty comparators. Their adjusted hazard ratio for MAKE was 36.6 (95% confidence interval, 31.6 to 42.4) versus the general population. The risk of developing MAKE declined over the first 5 years after posterior urethral valve diagnosis but remained elevated for >30-year follow-up. Children with posterior urethral valves were also at higher risk of death, CKD, long-term KRT, hypertension, and AKI than the general population or pyeloplasty comparators.

Conclusions: Children with posterior urethral valves are at higher risk of adverse long-term kidney outcomes well into adulthood.

Graphical abstract

Figure 1

Cumulative probability of MAKE among children diagnosed with posterior urethral valves versus general population comparators. MAKE were defined as a composite of all-cause mortality, long-term KRT (long-term dialysis or kidney transplant), or CKD. MAKE, major adverse kidney event; PUV, posterior urethral valve.

Figure 2

Smoothed HRs for long-term MAKE among children diagnosed with posterior urethral valves versus general population comparators by restricted cubic spline analysis. MAKE were defined as a composite of all-cause mortality, long-term KRT (long-term dialysis or kidney transplant), or CKD. The solid line represents the HR for MAKE over time after cohort entry, comparing children with posterior urethral valves versus the general population. The shaded area represents the pointwise 95% CIs for the corresponding HR. The markers indicate the position of four knots (with equal number of outcome events in each interval). The dashed line represents a HR of 1 (i.e., no significant difference in the hazard of MAKE between children with posterior urethral valves and general population comparators). The HR of MAKE was significantly elevated among children with posterior urethral valves than the general population throughout follow-up. The HR of MAKE declined over the first 5 years after posterior urethral valve diagnosis but remained elevated for >30-year follow-up. The CIs should be interpreted cautiously because they are not global CIs and thus not adjusted for multiplicity. CI, confidence interval; HR, hazard ratio.

Figure 3

Subgroup analyses for MAKE among children diagnosed with posterior urethral valves versus general population comparators. We evaluated for effect modification on the association between posterior urethral valve diagnosis and MAKE among the above subgroups using interaction terms (far right column) and stratified Cox proportional hazard models to determine HR for MAKE among children with posterior urethral valves versus general population comparator cohorts for each stratum. The proportional hazards assumption was violated in all subgroup models. The number of patients (second left column) indicates the proportion of the overall study population in each subgroup. For the first surgery subgroup, this indicates the number of children diagnosed with posterior urethral valves who underwent each procedure as their first surgery. For the first surgery subgroup analysis, the comparator cohort was divided into three equally sized cohorts (335,559 children) for comparison with each surgical intervention.