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

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.