Advances and challenges in kidney organoid modeling of inherited kidney diseases

Organoids are three-dimensional models derived from the directed differentiation of pluripotent stem cells, offering a revolutionary platform for mechanistic exploration of inherited kidney diseases, drug screening, regenerative medicine, and related fields. This review systematically outlines the stepwise induction of stem cell differentiation into kidney organoids containing nephron and ureteric bud structures through the simulation of key embryonic developmental signaling pathways, including Wnt and fibroblast growth factor. A key focus is placed on the application of this technology in modeling phenotypes of inherited kidney disorders such as polycystic kidney disease. Current challenges of kidney organoid models include the lack of vascularization limiting glomerular filtration function, significant batch effects compromising reproducibility and the absence of a comprehensive functional assessment system. Future directions require the integration of single-cell multi-omics, organ-on-a-chip technology, and artificial intelligence to optimize system compatibility and accelerate translation toward personalized medicine and alternative kidney transplantation therapies.