Genetics and ESKD Disparities in African Americans

Am J Kidney Dis. 2019 Dec;74(6):811-821. doi: 10.1053/j.ajkd.2019.06.006. Epub 2019 Oct 10.

Abstract

African Americans have a 2- to 4-fold greater incidence of end-stage kidney disease (ESKD) than whites, which has long raised the possibility of a genetic cause for this disparity. Recent advances in genetic studies have shown a causal association of polymorphisms at the apolipoprotein L1 gene (APOL1) with the markedly increased risk for the nondiabetic component of the overall disparity in ESKD in African Americans. Although APOL1-associated kidney disease is thought to account for a substantial proportion of ESKD in African Americans, not all the increased risk for ESKD is accounted for, and a complete cataloging of disparities in genetic causes of ESKD eludes our current understanding of genetic-associated kidney disease. Genetic testing aids the screening, diagnosis, prognosis, and treatment of diseases with a genetic basis. Widespread use of genetic testing in clinical practice is limited by the small number of actionable genetic variants, limited health literacy of providers and patients, and underlying complex ethical, legal, and social issues. This perspective reviews racial and ethnic differences associated with genetic diseases and the development of ESKD in African Americans and discusses potential uncertainties associated with our current understanding of penetrance of genetically linked kidney disease and population-attributable risk percent.

Keywords: African Americans; African ancestry; End-stage kidney disease (ESKD); angiotensin II type 1 receptor (AT1); angiotensin-converting enzyme (ACE); angiotensinogen (AGT); apolipoprotein L1 (APOL1); diabetes mellitus; diabetic nephropathy; genetic risk; glutathione-S-transferease Mu 1 (GSTM1); hypertension; kidney disease disparities; nephrin (NPHS1); racial disparities; renin angiotensin and aldosterone system (RAAS); review; risk allele; salt sensitivity; sickle cell disease (SCD); single-nucleotide polymorphism (SNP); uromodulin (UMOD).

Publication types

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

MeSH terms

  • Apolipoprotein L1 / genetics*
  • Black or African American / genetics*
  • Black or African American / statistics & numerical data
  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease / epidemiology*
  • Genetic Testing
  • Health Status Disparities
  • Healthcare Disparities / statistics & numerical data*
  • Humans
  • Kidney Failure, Chronic / ethnology*
  • Kidney Failure, Chronic / genetics*
  • Kidney Failure, Chronic / therapy
  • Kidney Transplantation / statistics & numerical data
  • Male
  • Needs Assessment
  • Renal Dialysis / statistics & numerical data
  • United States

Substances

  • Apolipoprotein L1