Advancing therapeutic approaches and shaping future perspectives in the management of autosomal dominant polycystic kidney disease (ADPKD): Insights from clinical trials

Abstract

Background

Autosomal dominant polycystic kidney disease (ADPKD) is a genetically inherited disorder characterized by progressive renal cyst formation, leading to end-stage renal disease (ESRD). The disease causes a continuous decline in renal function, resulting in significantly enlarged kidneys that adversely affect the patient's quality of life (QOL). Despite the identification of causative gene mutations, no approved therapeutic intervention halts cystogenesis or prevents renal failure.

Objectives

This review aims to evaluate the potential of emerging pharmacological interventions and investigational treatments to decelerate cyst growth and disease progression in ADPKD, with a focus on clinical trial outcomes and regulatory advancements.

Methods

Data from clinical trials (phases I-IV) were systematically reviewed to assess the effectiveness and safety of various therapeutic strategies for ADPKD. Mechanism-agnostic approaches, biomarker integration, and regulatory developments were also analyzed to understand their role in improving clinical management.

Results

Clinical studies indicate that pharmacological interventions and investigational therapies show promise in slowing cyst growth and disease progression. The U.S. FDA's adoption of mechanism-agnostic strategies and biomarker-based approaches has enhanced the framework for managing ADPKD. However, genetic heterogeneity and disease complexity remain significant barriers.

Conclusion

While a definitive cure for ADPKD remains elusive, recent therapeutic advancements provide hope for improving disease management and patient outcomes. Continued innovation and research are essential to overcome challenges in cystogenesis prevention and develop curative strategies.