Tolvaptan, a selective vasopressin V2 receptor antagonist, slows the increase in total kidney volume and the decline in kidney function in patients with polycystic kidney disease (PKD). However, it is unclear whether tolvaptan was able to delay progression to end-stage renal disease (ESRD). The present study examined the effects of short-term and long-term treatment in DBA/2FG-pcy mice, a model of nephronophthisis. With short-term treatment from 5 to 15 weeks of age, tolvaptan enhanced aquaresis, prevented increases in kidney weight and cyst volume, and was associated with significant reductions in kidney cyclic AMP levels and extracellular signal–regulated kinase activity. With long-term treatment from 5 to 29 weeks of age, tolvaptan attenuated the increase in kidney volume, reduced urinary albumin excretion, and reduced mortality to 20% compared with 60% in the control subjects. These data indicate that tolvaptan may delay the onset of ESRD in PKD by suppressing the increases in kidney volume and renal injury.
See article at J Pharmacol Exp Ther 2014, 349:258–267.
- Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics