Tolvaptan: A Review in Autosomal Dominant Polycystic Kidney Disease

Tolvaptan (Jinarc(®)) is a highly selective vasopressin V2 receptor antagonist indicated for use in patients with autosomal dominant polycystic kidney disease (ADPKD). Tolvaptan is the first pharmaceutical agent to be approved in Europe for delaying the progression of ADPKD in adults with stage 1-3 chronic kidney disease at initiation of treatment. In the large phase III TEMPO 3:4 trial in adults with ADPKD, 3 years' treatment with oral tolvaptan significantly reduced growth in total kidney volume and slowed renal function decline relative to placebo. Tolvaptan was also associated with a significantly lower rate of events for the composite secondary endpoint of time to investigator-assessed clinical progression relative to placebo, an effect that was largely attributable to reductions in the risk of worsening renal function and the risk of worsening kidney pain. Many of the most common adverse events in the tolvaptan group were related to its aquaretic mechanism of action (e.g. polyuria, nocturia, polydipsia and thirst). Tolvaptan was also associated with idiosyncratic elevations of liver enzymes which were reversible on discontinuation of the drug. Although the use of tolvaptan requires careful consideration and balancing of benefits and risks, current evidence suggests that tolvaptan is a promising new treatment option for patients with ADPKD.