Congenital anomalies of the kidney and urinary tract: defining risk factors of disease progression and determinants of outcomes

Abstract

Congenital anomalies of the kidney and urinary tract (CAKUT) result from disruptions in normal kidney and urinary tract development during fetal life and collectively represent the most common cause of kidney failure in children worldwide. The antenatal determinants of CAKUT are diverse and include mutations in genes responsible for normal nephrogenesis, alterations in maternal and fetal environments, and obstruction within the normal developing urinary tract. The resultant clinical phenotypes are complex and depend on the timing of the insult, the penetrance of underlying gene mutations, and the severity and timing of obstruction related to the sequence of normal kidney development. Consequently, there is a broad spectrum of outcomes for children born with CAKUT. In this review, we explore the most common forms of CAKUT and those most likely to develop long-term complications of their associated kidney malformations. We discuss the relevant outcomes for the different forms of CAKUT and what is known about clinical characteristics across the CAKUT spectrum that are risk factors of long-term kidney injury and disease progression.

Keywords: CAKUT; Kidney; Malformations; Nephrogenesis; Outcome; Risk factor.

Figure 1.

Converging risk factors in the fetus (genetics, maternal-fetal environments, and urinary tract obstruction) lead to a spectrum of kidney anomalies that result in variable loss of functioning nephrons. This reduction in nephron endowment can be further eroded by episodes of acute kidney injury (AKI) after birth, leading to adverse kidney outcomes of proteinuria, hypertension, and reduction in GFR.