Polycystic Kidney Disease-Related Mortality in the US (1999-2024): A Nationwide Joinpoint Analysis of Trends, Disparities, and Comorbidity Structure.

Introduction Polycystic kidney disease (PKD) is the most prevalent inherited kidney disorder and a major cause of kidney failure, yet national mortality data specific to it remain scarce. No study has characterized US PKD-related mortality trends across the full period of the International Classification of Diseases, Tenth Revision (ICD-10) mortality coding. Methods We conducted a serial cross-sectional analysis of death certificate data from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) Multiple Cause of Death database (bridged-race file 1999-2020; single-race file 2021-2024) among US adults aged 25 years and older. PKD-related deaths were identified by ICD-10 codes Q61.2 or Q61.3 recorded anywhere on the certificate. Age-adjusted mortality rates (AAMRs) per 100,000 (2000 US standard population) were stratified by sex, race and Hispanic origin, census region, age, urbanization, state, and place of death. Temporal trends were assessed with the Joinpoint Regression Program version 6.0.1 (grid search, 0-4 joinpoints; Monte Carlo permutation test, 4,499 permutations; log-linear model), reporting annual percent change (APC) and average APC (AAPC) with 95% CIs. Five hypotheses were specified before analysis. Results Between 1999 and 2024, 17,141 PKD-related deaths were recorded. The overall AAMR was 0.341 per 100,000 in 1999, fell to a nadir of 0.239 in 2013, and recovered to 0.311 by 2024. Joinpoint regression identified a single inflection in 2013: a 14-year decline (APC -3.01%; 95% CI, -4.00 to -2.01; p < 0.001) followed by an 11-year rise (APC +2.34%; 95% CI, +0.90 to +3.80; p = 0.003). The AAPC of -0.69% (p = 0.089) masked this two-segment trajectory. The reversal appeared across nearly all strata, with joinpoints clustered between 2008 and 2015, and was steepest among non-Hispanic Black decedents (segment-2 APC +4.17%; p = 0.010), approximately twice the non-Hispanic White rate (+2.07%). The Northeast was the only region without a significant rebound. Renal failure co-mention declined (AAPC -2.40%) while hypertension co-mention rose (AAPC +3.92%); ischemic heart disease co-mention declined (AAPC -2.45%). The underlying cause fell within the ICD-10 chapter containing PKD in 53.3% of classified deaths. Conclusions US PKD-related mortality reversed direction in 2013 after 14 years of decline. The reversal preceded the approval of ADPKD-specific therapy; its timing did not support a temporal association with the 2014 revision of kidney allocation policy. The rebound was numerically steepest among non-Hispanic Black decedents, and population-based co-mention rates shifted from renal failure toward hypertension.