Congenital anomalies of the kidney and urinary tract (CAKUT)

CAKUT manifest as a clinically broad spectrum of developmental anomalies of the kidneys, ureters, bladder, and urethra and are the leading cause of paediatric chronic kidney disease worldwide. Recognised phenotypes include kidney agenesis, hypodysplasia, multicystic dysplastic kidneys, vesicoureteral reflux, and obstructive uropathies. Detection is most commonly congenital, with anomalies identified by prenatal ultrasound or recognised at birth, although urinary-tract manifestations and progression to chronic kidney disease may also emerge later in childhood or in adulthood. Phenotypic heterogeneity is substantial across the spectrum, with clinical presentations ranging from incidental imaging findings in asymptomatic individuals to severe bilateral malformations associated with kidney failure in the perinatal period. Both nonsyndromic forms, in which anomalies are confined to the kidney and urinary tract, and syndromic forms, in which one or more extrarenal organ systems are also involved, are well recognised within the spectrum.

Due to insufficient data, no reliable statement on prevalence can currently be made. Approximately 16% of children with CAKUT are reported to have an identifiable monogenic cause.

Numerous genes are associated with CAKUT, and submicroscopic microdeletions and microduplications represent a further important mechanistic class. The genetic forms group into nonsyndromic and syndromic CAKUT; frequently identified causes include the following examples. Nonsyndromic forms include HNF1B-related kidney disease and Renal Coloboma Syndrome (PAX2-related). Syndromic forms include (EYA1) and HDR (Barakat) Syndrome (GATA3); variants in these genes are associated with progression to kidney failure.

The genetic conditions associated with CAKUT follow heterogeneous inheritance patterns. Recognised modes across the spectrum include autosomal dominant, autosomal recessive, and X-linked inheritance, with additional contributions from de novo variants and chromosomal or copy-number changes; a reliable proportional distribution across these modes is not currently established at the spectrum level.

• Where CAKUT is suspected to have a genetic cause, molecular genetic testing can identify the underlying condition and confirm a clinical suspicion.
• The identified entity guides further clinical management and is a prerequisite for targeted medical care; therapeutic options are evaluated individually by the treating physicians.
• Identification of the underlying pathogenic germline variant enables predictive testing of at-risk family members and provides information relevant to family planning.

• Liu JL, Wang XW, Liu CH, Gao DMX, Jiang XY, Mao JH, et al. Genetic spectrum of CAKUT and risk factors for kidney failure: a pediatric multicenter cohort study. Nephrol Dial Transplant. 2023;38(9):1981-91. doi:10.1093/ndt/gfac338. PMID:; PMCID:PMC10468753.
• Kagan M, Pleniceanu O, Vivante A. The genetic basis of congenital anomalies of the kidney and urinary tract. Pediatr Nephrol. 2022;37(10):2231-43. doi:10.1007/s00467-021-05420-1. PMID:.
• Hilger AC, Westland R, Hoefele J. Genetics of CAKUT. Med Genet. 2026;38(1):3-10. doi:10.1515/medgen-2025-2053. PMID:; PMCID:PMC12910339.