Integration of Genetics Into the Design and Conduct of Clinical Trials in Nephrology

Abstract

Advances in genomic diagnostics have enabled earlier and more precise identification of genetic kidney disease, but the translation of these insights into trial methodology and therapeutic development has lagged. This review examines the current challenges in nephrology trials—including disease heterogeneity, slow progression, and limited industry engagement—and explores how genomic information can address these barriers. Examples from trials in autosomal dominant polycystic kidney disease and other genetic kidney diseases demonstrate the feasibility and value of genomics-informed approaches, including genotype-based recruitment, post hoc genetic stratification, and drug repurposing. The emergence of genotype stratification, artificial intelligence tools, and gene-based therapies presents further opportunities to refine trial design and personalize treatment. However, incorporating genomics into clinical research also raises complex ethical and regulatory issues, including consent processes, data governance, and equitable access to testing and trial participation. As genomic testing becomes embedded in standard clinical practice, its alignment with clinical research infrastructure offers the potential to create a learning health system in nephrology. Realizing this potential will require cross-disciplinary coordination, international collaboration, and co-design with patients and communities. Integrating genetic nephrology into clinical trial conduct is not only feasible but essential to advancing precision medicine and improving outcomes for patients with kidney disease.