Tolvaptan in Polycystic Kidney Disease (ADPKD): the most exciting nephrology development in years

The High Impact Clinical Trials Session at this year's American Society of Nephrology Renal Week was the site of one of the most important and exciting nephrology developments to materialize in years. Researchers presented the results of a Phase 3 study using Tolvaptan (a vasopressin receptor antagonist) for the treatment of autosomal dominant polycystic kidney disease (ADPKD). Previously a disease with no medical treatment, ADPKD accounts for 10% of the dialysis population and is associated with pain, hematuria, hypertension and a number of extra-renal manifestations.

The Tempo 3:4 Study randomized 1445 patients to receive a mean dose of 95 mg of Tolvaptan versus placebo over a 3 year period of observation. Patients receiving active drug experienced a slowing of kidney volume by 50% and also a slower deterioration in GFR,  the primary and secondary outcomes of the study respectively. While there was a greater number of adverse effects related to the medication (polyuria, thirst, hyperuricemia, gout, hepatitis, hypernatremia), there were less ADPKD-related effects (pain, hemturia, urinary tract infection).

While the primary invstigator V. E Torrres was quick to temper enthusiasm until regulatory bodies such as the FDA weigh in on these findings, this study is a major breakthrough in the management of ADPKD and represents a shining example of bench to bedside research that will provide hope for a large group of patients who previously had no medical option for delaying the onset of end-stage renal disease in ADPKD. This will truly be a fascinating story to watch unfold as more study in this area continues.

Please see the New England Journal of Medicine publication here.