Tolvaptan and Autosomal Dominant Polycystic Kidney Disease Progression in Individuals Aged 18-35 Years: A Pooled Database Analysis.

Rational & Objective: Data are limited regarding the long-term efficacy of tolvaptan in adults aged 18-35 years with autosomal dominant polycystic kidney disease (ADPKD) at increased risk of rapid progression. We assessed the effects of tolvaptan within a larger population of younger adults and over longer follow-up than individual clinical trials could provide.

Study Design: Pooled database study.

Setting & Study Populations: A consolidated clinical study database with ADPKD patients aged 18-35 years.

Selection Criteria For Studies: Studies that enrolled patients who received either tolvaptan or standard-of-care treatment not including tolvaptan.

Data Extraction: Annual rate of change in estimated glomerular filtration rate (eGFR) and time to kidney failure.

Analytical Approach: For individuals participating in multiple studies, their data were longitudinally linked to extend the follow-up period. We matched tolvaptan-treated patients with controls based on age, sex, chronic kidney disease stage, eGFR, and, where possible, Mayo Imaging Classification. We compared eGFR decline between groups using mixed-effects modeling.

Results: The matched analysis set encompassed 204 tolvaptan-treated individuals and 204 controls. Median follow-up was 4.6 years for the tolvaptan group and 1.7 years for controls. In the mixed-effects model, the eGFR decline rate (in mL/min/1.73 m/year) was -2.58 for the tolvaptan cohort and -4.28 for controls. This indicates reduction in the eGFR decline rate by 1.69 mL/min/1.73 m/year (95% confidence interval: 0.87-2.52;  < 0.001) with tolvaptan, a 40% improvement. Extrapolating eGFR over 35 years, tolvaptan could delay kidney failure onset by approximately 11 years.

Limitations: Median follow-up was shorter in the control cohort than the tolvaptan cohort. The projection of time to kidney failure assumed a linear model of eGFR decline.

Conclusions: This analysis offers insights into the anticipated treatment benefits of tolvaptan for young adults with ADPKD. These findings are crucial for weighing treatment benefits against any associated risks.