Therapies in autosomal dominant polycystic kidney disease: beyond tolvaptan

Abstract

Purpose of review: Autosomal dominant polycystic kidney disease (ADPKD) is a progressive genetic disorder characterized by cyst formation, kidney enlargement, and eventual kidney failure. While tolvaptan remains the only FDA-approved therapy targeting disease progression, there is a growing pipeline of novel therapies. This review explores emerging interventions aimed at modifying cystogenesis, metabolic reprogramming, and kidney function decline.

Recent findings: Recent preclinical and early clinical studies have identified promising therapeutic avenues including AMPK activators (e.g., metformin), SGLT2 inhibitors, GLP-1 receptor agonists, and bempedoic acid. Dietary interventions such as ketogenic diets and caloric restriction show potential for reducing cyst burden and preserving kidney function. RNA-based therapies targeting miR-17 and PC1-correcting agents like VX-407 offer genetically targeted treatment approaches. Several of these interventions are in ongoing phase 2 or 3 clinical trials evaluating their safety and efficacy and are discussed in this review.

Summary: The treatment landscape for ADPKD is rapidly evolving, with multiple innovative therapies advancing toward clinical implementation. Integration of pharmacologic, dietary, and genetic strategies represents a comprehensive approach to modifying disease trajectory. Further large-scale, long-term studies are essential to validate these approaches and optimize individualized patient care.

Keywords: autosomal dominant polycystic kidney disease; gene therapy; ketogenic; micro-RNA; polycystin.