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.

Preventive Aspects of Early Resveratrol Supplementation in Cardiovascular and Kidney Disease of Developmental Origins

“…In addition to reduced nephron, impaired nephrogenesis can cause a wide spectrum of defects in the kidney and urinary tract, namely congenital anomalies of the kidney and urinary tract (CAKUT) [ 35 ]. Unlike adults, CAKUT is one of the major causes of CKD in children [ 36 ].…”

Developmental Origins of Kidney Disease: Why Oxidative Stress Matters?

“…The major developmental events include UB formation, UB branching morphogenesis, formation of bladder and kidney, kidney tubule branching, and nephrogenesis [ 49 ]. Impaired branching morphogenesis and nephrogenesis can cause low nephron endowment and a spectrum of defects in the kidney and urinary tract, namely congenital anomalies of the kidney and urinary tract (CAKUT) [ 50 ]. The developing kidneys are vulnerable to environmental risk factors that impair development throughout gestation: a malformed kidney is a severe defect happening during early pregnancy, whereas defects that occur later are generally less severe [ 50 ].…”

Bioenergetic Evolution Explains Prevalence of Low Nephron Number at Birth: Risk Factor for CKD

“…The corollary to this strategy is a prediction that unless severe, most subjects with low nephron number will not develop ESRD until after peak reproductive years, when selection pressure is low. 109 Consistent with this prediction, a Norwegian study of over 2 million subjects revealed that low birth weight, IUGR, and preterm birth represent cumulative risk factors for development of ESRD that is delayed until later adulthood. 110 The aging kidney.…”

“…108 Congenital anomalies of the kidneys and urinary tracts can result from genomic, epigenomic, or environmental stressors in any combination, and the more severe the nephron deficit, the sooner the onset of CKD and the more rapid its progression. 109 Human life history strategy favors allocation of energy to the developing brain through physiologic adaptation by the fetal cerebral circulation, 53 and by metabolic regulation of organ development by nuclear and mitochondrial gene transcription regulated epigenetically (Fig. 4).…”