Novel Insights into the Pathogenesis of Monogenic Congenital Anomalies of the Kidney and Urinary Tract

J Am Soc Nephrol. 2018 Jan;29(1):36-50. doi: 10.1681/ASN.2017050561. Epub 2017 Oct 27.

Abstract

Congenital anomalies of the kidneys and urinary tract (CAKUT) comprise a large spectrum of congenital malformations ranging from severe manifestations, such as renal agenesis, to potentially milder conditions, such as vesicoureteral reflux. CAKUT causes approximately 40% of ESRD that manifests within the first three decades of life. Several lines of evidence indicate that CAKUT is often caused by recessive or dominant mutations in single (monogenic) genes. To date, approximately 40 monogenic genes are known to cause CAKUT if mutated, explaining 5%-20% of patients. However, hundreds of different monogenic CAKUT genes probably exist. The discovery of novel CAKUT-causing genes remains challenging because of this pronounced heterogeneity, variable expressivity, and incomplete penetrance. We here give an overview of known genetic causes for human CAKUT and shed light on distinct renal morphogenetic pathways that were identified as relevant for CAKUT in mice and humans.

Keywords: CAKUT; congenital anomalies of the kidneys and urinary tract; genetic kidney disease; monogenic disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Congenital Abnormalities / genetics*
  • Extracellular Matrix / genetics*
  • Extracellular Matrix / metabolism
  • Humans
  • Morphogenesis / genetics*
  • Signal Transduction / genetics*
  • Urinary Tract / abnormalities*
  • Urinary Tract / embryology*