Roles for urothelium in normal and aberrant urinary tract development

Congenital anomalies of the kidney and urinary tract (CAKUTs) represent the leading cause of chronic kidney disease and end-stage kidney disease in children. Increasing evidence points to critical roles for the urothelium in the developing urinary tract and in the genesis of CAKUTs. The involvement of the urothelium in patterning the urinary tract is supported by evidence that CAKUTs can arise as a result of abnormal urothelial development. Emerging evidence indicates that congenital urinary tract obstruction triggers urothelial remodelling that stabilizes the obstructed kidney and limits renal injury. Finally, the diagnostic potential of radiological findings and urinary biomarkers derived from the urothelium of patients with CAKUTs might aid their contribution to clinical care. In this Review, Jackson and colleagues discuss the critical role of the urothelium in both normal urinary tract development and in congenital abnormalities of the urinary tract. Urothelial remodelling in congenital obstructive uropathy is also discussed. Key points Interactions between the developing urothelium and its underlying mesenchyme serve critical roles in developmental patterning of the bladder and ureter. Genetic disruption of signalling pathways that mediate terminal differentiation of urothelium and urothelial–mesenchymal interactions results in phenotypes of congenital abnormalities of the urinary tract in humans and mice. The urothelial plaque serves a critical protective role in response to congenital urinary tract obstruction. Urothelium-specific radiological and biochemical markers represent potential means of detecting congenital abnormalities of the urinary tract, but prospective studies are warranted to evaluate their diagnostic accuracy.