Kidney Organoids: Disease Modeling and Clinical Implementations for Patient Benefit

Background Progress in nephrology is still constrained by the limited ability of conventional experimental models to faithfully recapitulate the complex structure and function of the human kidney. Human pluripotent stem cells (hPSCs)-derived kidney organoids provide a 3D in vitro experimental system that allows investigation of kidney development and disease-related mechanisms in a human cellular context, although still limited in their ability to reproduce the full structural and physiological complexity of the native kidney. Summary Kidney organoids have emerged as a powerful system to investigate both inherited and acquired kidney disorders. Genetic applications include cystic kidney diseases and ciliopathies, as well as inherited tubular and storage disorders, and glomerular genetic diseases. For acquired diseases and injuries, organoids support modeling of kidney damage (including exposure to pathogenetic factors, metabolic, diabetic, and profibrotic stress) and drug nephrotoxicity. These platforms enable research on mechanistic pathways through transcriptomic, proteomic, imaging, and functional readouts that can be applied at the level of specific nephron segments. Methodological advances, including improved differentiation protocols and organoid-on-chip systems, are enhancing maturation and physiological relevance. Nevertheless, kidney organoids remain immature, showing variable cellular composition and lacking a fully integrated vasculature and urinary outflow system, which currently limit their applicability as experimental models. Key Messages Kidney organoids provide a human-based platform for mechanistic and translational nephrology research. At present, they are primarily used for disease modeling and nephrotoxicity testing, while their broader applicability remains limited by current technical and biological challenges. Regenerative translation will depend on advances in maturation and integration of fully developed vascular and urinary system components.