Autosomal-dominant polycystic kidney disease: tolvaptan use in adolescents and young adults with rapid progression

Background: The phase 3 Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes (TEMPO 3:4) clinical trial demonstrated the beneficial effect of tolvaptan on kidney growth and function in subjects aged 18–50 years over a 3-year period. However, it did not specifically assess the use of tolvaptan in adolescents and young adults (AYAs) with ADPKD. Methods: A post hoc analysis of the TEMPO 3:4 trials was performed for patients aged 18–24 years. The primary outcome was the annual rate of change in total kidney volume (TKV). The secondary outcome was to evaluate long-term safety of tolvaptan using Hy’s law of hepatotoxicity. Results: A total of 51 patients in the 18–24 age group were analyzed (tolvaptan: 29, placebo: 22). The tolvaptan group had a lower mean percentage of TKV growth per year compared to the placebo group (3.9% vs. 6.5%, P = 0.0491). For secondary outcomes, 63 patients in the AYA subgroup were evaluated. In both the AYA and adult groups, none of the patients met the criteria for Hy’s law of hepatotoxicity. Conclusions: This post hoc analysis suggests that tolvaptan, with appropriate patient selection and management, can provide effective and acceptably safe treatment in AYAs with ADPKD. Impact: Tolvaptan slows the increase in total kidney volume in patients aged 18–24 years with ADPKD.Tolvaptan posed no risk of potential liver injury measured via Hy’s law of hepatotoxicity in the AYA stratum.This study suggests that tolvaptan has beneficial outcomes in AYAs.This post hoc analysis suggests the need for additional studies with a larger pediatric patient population.The impact is significant as tolvaptan had not been specifically examined in the AYA patient population previously.