Congenital Anomalies of the Kidneys and Urinary Tract (CAKUT)

CAKUT is the most common cause of end-stage kidney disease (ESKD) in the pediatric population.

Phenotypic manifestations are broad and include:

• renal agenesis

• solitary kidney

• vesicoureteral reflux (VUR)

• posterior urethral valves (PUV)

• urinary tract obstruction

• horseshoe kidney

• multicystic dysplastic kidney (MCDK)

• renal dysplasia, renal hypoplasia, or both

Etiology is disordered renal embryogenesis:

• Renal development typically begins around the 5th week of gestation.

• Kidney tissue is derived from the intermediate mesoderm (pronephros, mesonephros, and metanephros). The metanephros is the primary tissue that results in kidney development and involves a complicated system of factors that result in the ureteric bud (collecting tubules, ducts, and ureters) invading the metanephric blastema (glomeruli, proximal and distal tubules, loop of Henle).

• After invasion, the ureteric bud continues to divide until the 36th week of gestation. Interruption of this intricate interaction may lead to lack of ureteric bud branching and renal hypoplasia. Dysregulation of ureteric bud branching leading to a gain of function may lead to ureteric duplication.

• Key genes involved include PAX2 (renal coloboma syndrome) and EYA1 (branchio-oto-renal syndrome).

Evaluation relies on an accurate history and physical, baseline renal imaging, and assessment for any extrarenal manifestations that may lead to a diagnosis of syndromic CAKUT (conditions in which other organ systems besides the kidney, ureter, and bladder are affected).

Prognosis is varied and depends on the etiology of CAKUT:

• Patients with renal ectopy, multicystic dysplastic kidney, and solitary kidney typically have a good prognosis, with normal glomerular filtration rate (GFR) and metabolic balance, but may be at increased risk for the development of hypertension or proteinuria as adults, and require periodic monitoring and imaging to assess for renal growth.

• Patients with known obstruction, PUV, and VUR from birth have various grades of severity and can present with mild chronic kidney disease (CKD) or may require renal transplant and dialysis at a young age.