Therapies in autosomal dominant polycystic kidney disease: beyond tolvaptan

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 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.

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.