A Primer on Congenital Anomalies of the Kidneys and Urinary Tracts (CAKUT)

Abstract

Congenital anomalies of the kidneys and urinary tracts (CAKUT) are disorders caused by defects in the development of the kidneys and their outflow tracts. The formation of the kidneys begins at week 3 and nephrogenesis continues until week 36, therefore, the kidneys and outflow tracts are susceptible to environmental risk factors that perturb development throughout gestation. Many genes have been implicated in kidney and outflow tract development, and mutations have been identified in patients with CAKUT. In severe cases of CAKUT, when the kidneys do not form, the fetus will not survive. However, in less severe cases, the baby can survive with combined kidney and outflow tract defects or they may only be identified in adulthood. In this review, we will cover the clinical presentation of CAKUT, its epidemiology, and its long-term outcomes. We will then discuss risk factors for CAKUT, including genetic and environmental contributions. Although severe CAKUT is rare, low nephron number is a much more common disorder with its effect on kidney function increasingly apparent as a person ages. Low nephron number appears to arise by the same mechanisms as CAKUT, but it differs in terms of the magnitude of the insult and the timing of when it occurs during gestation. By understanding the causes of CAKUT and low nephron number, we can begin to identify preventive treatments and establish clinical guidelines for how these patients should be followed.

Keywords: CAKUT; congenital anomalies of the kidney and urinary tract; development; environment; epigenetics; fetus; genetics; infant; kidney malformations; longitudinal studies; mutation; nephrons; pediatric nephrology; risk factors; urogenital abnormalities; vesicoureteral reflux.

Figure 1.

CAKUT defects can occur throughout fetal development, with more severe defects emerging earlier in development. Major developmental events in the formation of the kidneys and urinary tract including ureteric bud formation, ureter extension and kidney formation, bladder formation, kidney tubule branching and nephrogenesis (shown as an inset at 8 weeks), and ureterovesical junction formation. CAKUT defects are shown within the time window in which they are most likely to occur. Our timeline is based on findings from Potter (58) and Vize et al. (59).

Figure 2.

CAKUT defects can be identified through radiological findings. Kidney hypoplasia: a small malformed kidney depicted in the cartoon corresponding to the adjacent ultrasound of a small hyperechoic kidney, indicated by an asterisk (*). Multicystic dysplastic kidney: a kidney with dysplastic tissue and multiple cysts. Dark fluid-filled sacs representing cysts are seen throughout the kidney on ultrasound. Duplex kidney: duplex kidney shows two ureters on the left with a dilated ureter attached to the upper pole. The ultrasound shows dilation of the upper pole indicated by a red arrowhead. Vesicoureteric reflux: reflux is shown with dilated ureters entering the kidneys. The adjacent image shows a voiding cystourethrogram which is performed by injecting a radio-opaque agent into the bladder. An enlarged bladder (star) is shown with dilated tortuous ureters (black arrow heads) refluxing urine to the kidneys. Ureteropelvic junction obstruction: obstruction at the connection between the ureter and kidney, causing hydronephrosis in the kidney seen on ultrasound. Posterior urethral valve: congenital obstruction of urethra results in abnormal bladder. Adjacent voiding cystourethrogram shows a distended irregular bladder (black arrows) and dilated prostatic urethra.