Congenital anomalies of the kidney and urinary tract (CAKUT)

Congenital anomalies of the kidney and urinary tract (CAKUT) comprise a wide spectrum of structural and functional malformations leading to defective morphogenesis of the kidneys and/or the efferent urinary tract. The phenotypic spectrum ranges from vesicoureteral reflux to renal agenesis. CAKUT may occur in isolation or in association with complex malformation syndromes. Clinical manifestations can include abnormalities of the urinary tract, lower urinary tract obstruction (LUTO)/megacystis, and renal agenesis or hypoplasia.

CAKUT are observed in about 3–6 per 1,000 newborns and represent the main cause of chronic kidney failure in children.

In approximately 6% of cases, numerical abnormalities of entire chromosomes are causative, including trisomies 13, 18 and 21, as well as Ullrich–Turner syndrome. Copy number variations, such as microdeletions or microduplications, are detected in about 10–15% of CAKUT patients, most frequently involving chromosomal regions 1q21.1, 16p11.2, 17q12 and 22q11.2. In 10–20% of cases, pathogenic variants in single genes can be detected, most commonly affecting HNF1B and PAX2 (approximately 5% of cases). Overall, around 50 genes are known to be associated with CAKUT, and depending on the clinical presentation, requesting a corresponding subpanel may be advisable in some cases.

Diagnosis is based on the identification of congenital structural or functional anomalies of the kidneys and urinary tract. Depending on the clinical presentation, targeted genetic subpanels may be appropriate, including panels focusing on malformations of the urinary tract, renal agenesis or hypoplasia, or lower urinary tract obstruction (LUTO), megacystis, or anal atresia.

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• Saisawat et al. 2011, Kidney Int 81:196