Pooled Data Analysis of the Long-Term Treatment Effects of Tolvaptan in ADPKD

Introduction: In 1-and 3-year randomized trials, tolvaptan slowed kidney function decline in subjects with autosomal dominant polycystic kidney disease (ADPKD) at risk of rapid progression. The 3-year trial also evaluated effects on total kidney volume (TKV); slowing of TKV growth was demonstrated. Subjects were followed in open-label extension trials. To characterize longer-term effects of treatment, an analysis was conducted comparing tolvaptan-treated subjects with subjects from standard of care (SOC) ADPKD studies without tolvaptan. Methods: This was a pooled, longitudinal analysis of data from 8 tolvaptan clinical trials and 5 studies without tolvaptan (natural history or SOC) in ADPKD. Data from subjects who participated in multiple studies were linked for longer follow-up. Outcomes were rates of change in estimated glomerular filtration rate (eGFR) and TKV over 5.5 years. To control for heterogeneity in disease characteristics between tol-vaptan and SOC treatment groups, analysis populations matched for baseline demographic and disease characteristics were constructed. Results: Matched analysis (n = 1186 in each treatment group) indicated that tolvaptan slowed annualized eGFR decline by 1.01 ml/min per 1.73 m(2) (P < 0.001) versus SOC over 5.5 years. An analysis conducted on the full, unmatched data set (tolvaptan: n = 2928; SOC: n = 4189) confirmed significant reduction in annual eGFR decline. Among subjects with TKV data, TKV was significantly reduced at years 1, 3, and 5 for tol-vaptan versus SOC in both matched and full data sets. Conclusion: Comparison of a pooled tolvaptan cohort to a pooled control cohort with ADPKD supports longer-term treatment effects of tolvaptan.(C) 2022 International Society of Nephrology. Published by Elsevier Inc.