Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is the fourth most common cause of end-stage renal failure and the causative condition in approximately 8% of patients requiring renal replacement therapy in Europe. According to the latest epidemiological data in Italy, about 25,000 individuals are affected by ADPKD. In February 2015, the European Medicines Agency (EMA) approved the use of tolvaptan (JINARC®) for the treatment of ADPKD. Tolvaptan is a selective antagonist for the V2 receptor of vasopressin. It induces the reduction of renal cyst size and kidney volume; furthermore, it restrains cystic cell proliferation. TEMPO 3:4 is a large phase III study that demonstrated the clinical efficacy of tolvaptan in reducing renal volume and slowing renal function loss. The TEMPO 4:4 extension study evaluated for a further two years tolvaptan's safety features and efficacy in patients previously enrolled in TEMPO 3:4. The safety profile emerging from TEMPO 4:4 confirmed the safety and tolerability of this molecule. The most significant clinical safety issue concerns liver toxicity; this occurs in less than 4% of subjects and requires specific monitoring. Post hoc analysis adjusted for major confounders suggested the ability of tolvaptan to retain its therapeutic efficacy even in the extension period. Tolvaptan is the first molecule with proven efficacy in ADPKD; in view of the potential toxicity and the significant aquaretic effect, which reduces the patient's quality of life, the treatment should be directed to a selected population with evidence of rapidly progressive disease.