Chronic kidney disease affects 10% of Americans. Over 700,000 receive dialysis. The long-term prognosis for the dialysis patient is poor. A renal transplant can provide a cure but there are too few kidneys to meet the need. Our studies have taken two distinct directions towards the goal of improving outcomes for kidney patients: understanding how the human kidney is built to be able to replicate normal developmental strategies to synthesize new kidney structures and examining injury-invoked repair processes in the mammalian kidney to better understand normal repair processes: the cell types and molecular mechanisms, the limits to repair, and the relationship between failed repair, fibrosis and the progression of chronic kidney disease.
Our analysis of the developing human kidney has provided the first comprehensive insight into developmental processes highlighting molecular and cellular events shared with the well-studied mouse model, but unique human features. The insights here will be critical to optimizing strategies to generate normal human kidney structures from pluripotent stem cells (PSCs). To this end, we employed genetic tagging strategies to facilitate the isolation of key cell types from PSC-derived human kidney organoids demonstrating that cells generated in the tissue culture dish have remarkable similarities to their counterparts within the normal kidney. Kidney organoids not only provide a mechanism to obtain relevant renal cell types to move translational efforts forward but they can also model renal disease as we have shown with a PSC-directed, kidney organoid model of polycystic kidney disease, a leading genetic cause of end stage renal disease.