Tolvaptan safety in autosomal-dominant polycystic kidney disease; a focus on idiosyncratic drug-induced liver injury liabilities

Toxicol Sci. 2025 Jan 1;203(1):11-27. doi: 10.1093/toxsci/kfae142.

Abstract

Tolvaptan is a vasopressin V2 receptor antagonist which has proven to be an effective and mostly well-tolerated agent for the treatment of autosomal-dominant polycystic kidney disease. However, its administration is associated with rare but serious idiosyncratic liver injury, which has warranted a black box warning on the drug labels and frequent monitoring of liver blood tests in the clinic. This review outlines mechanistic investigations that have been conducted to date and constructs a working narrative as an explanation for the idiosyncratic drug-induced liver injury (IDILI) events that have occurred thus far. Potential risk factors which may contribute to individual susceptibility to DILI reactions are addressed, and key areas for future investigative/clinical development are highlighted.

Keywords: ADPKD; T-cell; drug induced liver injury; hypersensitivity; idiosyncratic; tolvaptan.

Publication types

  • Review

MeSH terms

  • Animals
  • Antidiuretic Hormone Receptor Antagonists* / therapeutic use
  • Chemical and Drug Induced Liver Injury* / etiology
  • Humans
  • Polycystic Kidney, Autosomal Dominant* / drug therapy
  • Risk Factors
  • Tolvaptan* / therapeutic use

Substances

  • Tolvaptan
  • Antidiuretic Hormone Receptor Antagonists