Tolvaptan for patients with ADPKD

by Dr. Lazowski

Tolvaptan has received clearance for a treatment of autosomal dominant polycystic kidney disease (ADPKD) in adults. The drug is marketed as Jynarque by Otsuka Pharmaceutical Company and was originally used for a treatment of hyponatremia. This drug which inhibits vasopressin V2 receptor, slowed kidney function decline in patients with ADPKD. In the TEMPO trial, the drug has shown close to 40% reduction of the rate of increase in total kidney volume. In 1445 patients, aged 18-50 years, who had ADPKD and creatinine clearance of 60 ml/min or more, Tolvaptan, has been shown to significantly decrease the rate of decline in eGFR by 1ml/min/year compared with placebo recipients. Patients who were taking Tolvaptan experienced a significant increased risk of liver toxicity, presenting with elevated liver enzymes but without any cases of serious and irreversible liver damage. In another trial, REPRISE (Replicating Evidence of Preserved Renal function: an Investigation of Tolvaptan Safety and Efficacy in ADPKD), a double-blind, placebo controlled, multi center investigation, 1370 ADPKD were enrolled. Tolvaptan treatment slowed progression of renal disease by 1.27ml/min per year, which would extend the time of progression to CKD stage V from 6.2 to 9 years. This drug is the first medication that offers effective treatment for patients with autosomal dominant polycystic kidney disease. These studies suggest a clinically meaningful ability of Tolvaptan to improve quality of life by delaying cyst growth. It also delays the need for kidney transplantation and/or dialysis by slowing decline of renal function. However the drug comes with an average wholesale cost of $13,041 per 28 days and its use might thus be restricted to patients with rapidly progressing disease. New England Journal of Medicine (2017;6;377:1930-1942). Renal and Urology News, Vol 17, issue number 3, May/June 2018 https://www.jynarquehcp.com/mechanism-of-action