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Kidney diseases are a major problem worldwide and the number of patients with chronic kidney diseases and acute or chronic renal failure are rising each year (1). Hemodialysis and peritoneal dialysis are used to replace the detoxification function of kidneys in patients with end-stage renal disease (ESRD). Although these treatments are life-preserving, they are associated with a marked impairment of quality of life and fail to replace important kidney functions, such as endocrine activities (renin, erythropoietin, and activation of vitamin D) and fine regulation of electrolyte/water homeostasis. Kidney transplantation is so far the only option to restore all aspects of normal kidney function, providing much better quality of life and longer survival compared with dialysis. However, there is a severe shortage of human donor organs: in the United States ∼17,000 kidney transplantations were done in 2014, but at least fivefold more patients are on the waiting list, and each day 12 people die while waiting for a life-saving kidney transplant (2). Alternatives to human kidney transplants from living or deceased donors are thus urgently needed. Current strategies include xenotransplantation of kidneys from genetically engineered donor pigs (reviewed in ref. 3), use of extracorporal bioartificial kidneys with tubular cells grown in hollow fiber devices (4), development of bioengineered kidneys by repopulating the decellularized scaffold of cadaveric organs with endothelial and epithelial cells (5), and de novo kidney generation from stem cells and embryonic progenitor tissues (reviewed in ref. 6). In PNAS, Yokote et al. (7) use an elegant isogenic pig model system to demonstrate that functional de novo kidneys of sufficient size for human transplantation can be generated in principle, and that urine excretion can be facilitated by development of a stepwise peristaltic ureter (SWPU) system. Because of its complex architecture and composition of numerous highly specialized and differentiated cell types, …

Pigs pave a way to de novo formation of functional human kidneys