Preclinical evaluation of tolvaptan and salsalate combination therapy in a Pkd1-mouse model.

ABSTRACT: Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disorder and an important cause of end stage renal disease (ESRD). Tolvaptan (a V2R antagonist) is the first disease modifier drug for treatment of ADPKD, but also causes severe polyuria. AMPK activators have been shown to attenuate cystic kidney disease. Methods: In this study, we tested the efficacy of the combined administration of salsalate (a direct AMPK activator) and tolvaptan using clinically relevant doses in an adult-onset conditional Pkd1 knock-out (KO) mouse model. Results: Compared to untreated Pkd1 mutant mice, the therapeutic effects of salsalate were similar to that of tolvaptan. The combined treatment tended to be more effective than individual dru

SUBMITTER: Song X 

PROVIDER: S-EPMC9893022 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature