The effect of tolvaptan on autosomal dominant polycystic kidney disease patients: a subgroup analysis of the Japanese patient subset from TEMPO 3:4 trial

Background: Japan is the first country in the world to approve tolvaptan for the treatment of autosomal dominant polycystic kidney disease (ADPKD), which was based on the results of Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes (TEMPO) 3:4 trial. To evaluate the safety and efficacy of tolvaptan, we performed a subgroup analysis in the participating Japanese ADPKD patient population. Methods: The primary outcome was the annual rate of percentage change in the total kidney volume (TKV). The secondary endpoint was the rate of kidney function change. Results: The tolvaptan and placebo groups included 118 and 59 patients, respectively. The annual rate of percentage changes in TKV were 1.3 % [95 % confidence interval (CI) 0.4–2.1] in the tolvaptan group, and 5.0 % (95 % CI 3.9–6.2) in the placebo group (P < 0.001). The annual estimated glomerular filtration rate change was −3.83 mL/min/1.73 m² in the tolvaptan group and −5.05 mL in the placebo group for a treatment effect of +1.22 mL/min/1.73 m² (95 % CI 0.41–2.02: P = 0.003). Hepatic function abnormal as a serious adverse event was observed in 3 patients (2.5 %) in the tolvaptan group. Conclusions: Administration of tolvaptan in the Japanese sub-population reduced the annual rate of TKV growth and slowed the rate of kidney function decline over 36 months compared to patients on placebo, thus providing a novel and effective therapy for the treatment of ADPKD. (TEMPO 3:4 ClinicalTrials.gov number, NCT00428948).