Safety and efficacy of tolvaptan in real‑world Japanese patients with autosomal dominant polycystic kidney disease: final results of SLOW‑PKD surveillance.

Background: Tolvaptan, a vasopressin type 2 receptor antagonist, has been used to treat autosomal dominant polycystic kidney disease in Japan since 2014.

Methods: This long-term, real-world, post-marketing surveillance (PMS) was conducted in Japan from March 2014 to March 2022. Safety was assessed based on adverse drug reactions (ADRs). For efficacy, changes in the slope of total kidney volume (TKV) and estimated glomerular filtration rate (eGFR) were assessed before and during the administration of tolvaptan.

Results: A total of 1676 patients were enrolled, with mean TKV (n = 1000) of 2149 ± 1339 mL and eGFR (n = 1641) of 44.4 ± 21.7 mL/min/1.73 m². Frequent ADRs were hepatic function abnormal (9.6%), hyperuricaemia (8.3%), and thirst (8.1%). Most of the increased alanine aminotransferase exceeding 3 times the upper limit of the reference level occurred from 3  to  14 months after the start of treatment, but about 20% was observed after 15 months. There was no increase in ADRs over 36 months, suggesting that no other safety concerns need to be monitored during administration over 3-7 years. The mean slope of the estimated TKV increase before and during tolvaptan treatment was 6.58 and 3.71%/year, respectively (P = 0.0020). The mean slope of eGFR decline was - 3.63 and - 3.26 mL/min/1.73 m²/year, respectively (P = 0.2728).

Conclusion: There were no major problems with the safety of tolvaptan treatment, and efficacy in limiting TKV increase in this PMS was comparable to the previous, pivotal randomized control trials. Trial registration ClinicalTrials.gov; NCT02847624.