Treatment of autosomal dominant polycystic kidney disease (ADPKD) – Tolvaptan

Abstract

The European Medicines Agency approved tolvaptan to slow cyst growth and renal failure progression in adults with ADPKD, glomerular filtration ≥60 mL/min x 1.73 m2 and rapidly progressive disease. In a multicenter 3-year study, conducted on 1,445 patients with non-genotyped ADPKD, ages 18-50 years, predicted creatinine clearance ≥60 mL/min and kidney total volume ≥750 mL, tolvaptan slowed kidney failure progression (-23%-46% for different objectives) and reduced kidney volume increase and pain without effects on hypertension and albuminuria.Tolvaptan induced reversible idiosyncratic hepatopathy in 4% of patients (1% in placebo). Tolvaptan antagonizes ADH effects, reduces cyclic-AMP generation in distal nephron, and induces water diuresis. It has high protein-binding and 8-hour half-life. Dosage is 60-120 mg/day in two different doses (for instance 45/15 or 60/30 mg). Treatment starts using lower dose and continues with cautious up-titolation. Data are insufficient for severe hepatopathy or nephropathy. There is no antidote against overdose. Dialysis should not remove tolvaptan. Aquaretic effects require high fluid intake to prevent dehydration. Treatment should be reduced or suspended in case of inadequate fluid intake or dehydration. Weight, natremia and plasma osmolality can inform on dehydration risks. Efficacy is not yet investigated on end-stage renal disease, non-renal ADPKD-related disorders, and mortality.

Key words: Tolvaptan, adult polycystic kidney disease, creatinine, kidney volume

Full text of the article is available in Italian.