Congenital anomalies of the kidney and urinary tract (CAKUT)

Abstract

Congenital anomalies of the kidney and urinary tract (CAKUT) are wide spectrum of prenatal malformations (isolated or as a part of syndromes), accounting for up to one quarter of overall birth defects and causes end-stage renal disease in up to a half of these cases. The most sever CAKUT phenotypes arise from a disturbed differentiation or interaction of the ureteric bud and the metanephric mesenchyme. CAKUT can be triggered through interplay of various genetic and epigenetic factors, as well as by numerous extrinsic factors including maternal diabetes, medications, and folate and iron deficiency, highlighting environmental factors that modify expression of disease. Genetic impairments (about 40 monogenic isolated and about 150 as a part of a syndrome) underlay about 15% of cases with variable expressivity and incomplete penetrance. Copy number variations (CNVs) and submicroscopic chromosomal imbalances are diagnostic challenge. Early identification of mutations in genes which can lead to CAKUT can facilitate targeted therapy. Gene panels based on next generation sequencing technology (NGS) might elucidate and significantly improve the process of testing and may lead to proper and thereby more effective diagnosis of CAKUT.