congenital anomalies of the kidney and urinary tract

Almost 50% of children with end-stage kidney disease have congenital abnormalities of the kidney and urinary tract. These abnormalities arise in about three to six per 1000 livebirths and constitute 20–30% of all anomalies identified in neonates.

Congenital abnormalities of the kidney and urinary tract (CAKUT) occur in 1 out of 500 newborns, and constitute approximately 20-30% of all anomalies identified in the prenatal period.

CAKUT has a major role in renal failure, and there is increasing evidence that certain abnormalities predispose to the development of hypertension and cardiovascular disease in adult life.

Congenital anomalies of the kidney and urinary tract (CAKUT) account for one third of all anomalies detected by routine fetal ultrasonography.

CAKUT is the cause of 40% of childhood end-stage renal failure. Acquired glomerulonephritis and congenital nephrotic syndromes, respectively, accounted for just 18% and 8% of cases, with other diseases being rare (nephronophthisis, 5%; cystinosis, 3%; polycystic kidney diseases [PKDs], 3%).

The spectrum of diseases encompassed by the term "CAKUT" is wide, including:

 fetal kidney anomalies (renal malformations)

• renal agenesis (renal aplasia)
• renal hypoplasia
• multicystic dysplastic kidneys (renal dysplasias) (MRDs)

 fetal ureteric anomalies

• megaureter
• ureteropelvic junction obstruction (UPJO)
• ureterovesical junction obstruction
• ureterovesical junction incompetence
• duplex kidneys/ureters (renal duplications)

 fetal vesical anomalies (anaomlies of the bladder)
 fetal urethral anomalies

Etiology (Examples)

 ISL1 deletion

 disruption of ROBO2 in congenital anomalies of the kidney and urinary tract (CAKUT), as vesicoureteral reflux (VUR). (17357069)

Mutations in many different single genes can cause a wide phenotypic spectrum of congenital abnormalities of the kidney and urinary tract.

Disease phenotypes include renal agenesis, renal hypodysplasia, multicystic or dysplastic kidney, hydronephrosis, ureteropelvic junction obstruction, megaureter, ureter duplex or fissus, prevesical stenosis, and vesicoureteral reflux.

These congenital abnormalities might present as an isolated feature or as part of clinical syndromes in association with extrarenal manifestations—eg, branchio-otorenal syndrome or Kallman’s syndrome.

The pathological basis of congenital abnormalities of the kidney and urinary tract is the disturbance of normal nephrogenesis, possibly as a result of mutations in genes that govern the process.

Many of these genes encode transcription factors, which might partly account for the variable expression.

In the future, most forms of congenital abnormalities of the kidney and urinary tract are likely to be shown to be the result of many rare single-gene defects, which will allow important advances in diagnostic tests.

Congenital anomalies of the kidneys and urinary tract (CAKUT) are frequently associated with malformations of other organs.

Cytogenetics

10% of patients with syndromic CAKUT were shown to carry DNA microimbalances (20605837), and four chromosomal regions presumably associated with the CAKUT phenotype are identified (20605837):

 1q21.1 (duplication of 2.73 Mb)
 2q37.1-q37.3 (9.52 Mb gain)
 3q23-q25.1 (de novo loss of 13.38 Mb including the AGTR1 gene)
 7q36.2-q36.3 (terminal 5.65 Mb loss - unbalanced 2;7-translocation)

See also

 renal genetic diseases

References

 Islet1 Deletion Causes Kidney Agenesis and Hydroureter Resembling CAKUT. Yusuke Kaku et al.JASN 2013, doi : Link)

 Mapping candidate regions and genes for congenital anomalies of the kidneys and urinary tract (CAKUT) by array-based comparative genomic hybridization. Weber S, Landwehr C, Renkert M, Hoischen A, Wühl E, Denecke J, Radlwimmer B, Haffner D, Schaefer F, Weber RG. Nephrol Dial Transplant. 2010 Jul 5. PMID: 20605837

 Schedl A. Renal abnormalities and their developmental origin. Nat Rev Genet. 2007 Oct;8(10):791-802. PMID: 17878895