Renal development in the fetus and premature infant

Abstract

Congenital abnormalities of the kidney and urinary tract (CAKUT) are one of the leading congenital defects to be identified on prenatal ultrasound. CAKUT represent a broad spectrum of abnormalities, from transient hydronephrosis to severe bilateral renal agenesis. CAKUT are a major contributor to chronic and end stage kidney disease (CKD/ESKD) in children. Prenatal imaging is useful to identify CAKUT, but will not detect all defects. Both genetic abnormalities and the fetal environment contribute to CAKUT. Monogenic gene mutations identified in human CAKUT have advanced our understanding of molecular mechanisms of renal development. Low nephron number and solitary kidneys are associated with increased risk of adult onset CKD and ESKD. Premature and low birth weight infants represent a high risk population for low nephron number. Additional research is needed to identify biomarkers and appropriate follow-up of premature and low birth weight infants into adulthood.

Keywords: Congenital abnormalities of the kidney and urinary tract (CAKUT); Fetal ultrasonography; Hydronephrosis; Prematurity; Renal development; Urinary tract obstruction.

Fig. 1

Genetic, epigenetic, and environmental factors interact to modify renal developmental pathways and lead to a spectrum of congenital abnormalities of the kidney and urinary tract (CAKUT). VUR, vesicoureteral reflux; UPJ, ureteropelvic junction; UVJ, ureterovesical junction.

Fig. 2

Studies suggest genetic factors, including major chromosomal anomalies, copy number variants (CNV), and monogenic mutations/deletions likely contribute to up to 45% of congenital abnormalities of the kidney and urinary tract (CAKUT). Environmental factors, including an adverse fetal environment, and not yet discovered genetic factors likely contribute to the remainder.