Congenital Anomalies of the Kidney and Urinary Tract

Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) is a developmental disorder of the kidney and/or genitourinary tract. CAKUT accounts for up to 50% of end-stage kidney disease (ESKD) in childhood and between 7% and 10% of adult-onset ESKD. CAKUT can occur in isolation or in association with extrarenal features of disease, which is sometimes referred to as syndromic CAKUT. The pathogenesis of CAKUT is due to disturbances in the various stages of the embryonic development of either the kidney or genitourinary tract, which can results in a heterogeneous range of disease phenotypes. Despite polygenic and environmental factors being implicated, a significant proportion of CAKUT is monogenic in origin with studies demonstrating single gene defects in approximately 10–20% of patients with CAKUT. Multiple molecular pathways have been implicated in CAKUT including the RET tyrosine kinase signaling system, the Fraser complex and the extracellular matrix complex, and more recently, the vitamin A and retinoic acid signaling pathway.