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Updated: Sep 8, 2025

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
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Long-Term Experience of Tolvaptan: Is Hepatotoxicity Still a Concern?

Pierre Antoine Brown1, Suzy Bubolic2, Annick Laplante2

  • 1Division of Nephrology, Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.

Kidney360
|July 21, 2025
PubMed

Insights

Tolvaptan effectively slows kidney disease progression in autosomal dominant polycystic kidney disease (ADPKD). Frequent liver monitoring in Canada prevented serious liver injury in over 2800 patients over 10 years.

Area of Science:

  • Nephrology
  • Pharmacology
  • Hepatology

Background:

  • Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by kidney enlargement and function decline.
  • Tolvaptan (JINARC®) is approved in Canada to slow ADPKD progression.
  • The TEMPO 3:4 study indicated a potential risk of liver injury with tolvaptan.

Purpose of the Study:

  • To review the hepatic safety profile of tolvaptan in ADPKD patients.
  • To evaluate the effectiveness of the Canadian Hepatic Safety Monitoring and Distribution (HSMD) Programme.
  • To assess real-world evidence on tolvaptan-induced liver injury (DILI).

Main Methods:

  • Review of clinical trial data on tolvaptan's hepatic safety.
  • Analysis of data from the Canadian HSMD Programme.
  • Examination of real-world evidence from patients treated with tolvaptan.

Main Results:

  • Frequent liver function monitoring enables early detection of DILI.
  • Prompt treatment interruption is crucial for managing potential liver injury.
  • The HSMD Programme has successfully prevented serious liver injury or failure in over 2800 Canadian patients treated with tolvaptan over 10 years.

Conclusions:

  • Tolvaptan is a valuable treatment for slowing ADPKD progression.
  • Robust safety monitoring programs are essential for managing drug-induced liver injury.
  • The Canadian experience demonstrates the safety and efficacy of tolvaptan when managed with vigilant hepatic monitoring.
Keywords:
ADPKD

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