Kidney Development and Related AnomaLies

In mammals, three pairs of kidneys develop at different embryonic time points. These are pronephros, mesonephros, and metanephros. The pronephros and mesonephros are transient structures; the metanephros persists and matures into the adult kidney. Molecular and developmental regulation of this process is highly intricate and precise as disruption at different stages results in congenital anomaLies of the kidneys or the lower urinary tract (CAKUT). CAKUT are a wide group of anomaLies that can occur individually, coexist, or be present in syndromes with involvement of other organs. These anomaLies are the most common cause of renal failure in children and a significant cause of end-stage renal disease in adult patients. Studies in rodents have demonstrated similarities in the development of the human and rodent kidneys and have shown how the epitheLial and mesenchymal compartments synergize to form a normal kidney and ureter. Several mouse models were analyzed that identify genes necessary for kidney and urinary tract development. Many of the phenotypes observed in mutant mice are reminiscent of human CAKUT and provided key insights into the pathogenesis of these anomaLies. In some cases, mutations in these genes were also identified in patients. Here, we review the events in normal kidney development and then discuss specific examples of human CAKUT with focus on their pathophysiological basis. We describe the major genes and pathways important in CAKUT and discuss promises and challenges in the genomics of CAKUT.