Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Nov;72(5 Suppl 1):S8-S16.
doi: 10.1053/j.ajkd.2018.06.020.

APOL1-Associated Nephropathy: A Key Contributor to Racial Disparities in CKD

Barry I Freedman  1 , Sophie Limou  2 , Lijun Ma  3 , Jeffrey B Kopp  4
Affiliations
Review

APOL1-Associated Nephropathy: A Key Contributor to Racial Disparities in CKD

Barry I Freedman et al. Am J Kidney Dis. 2018 Nov.

Abstract

Genetic methodologies are improving our understanding of the pathophysiology in diverse diseases. Breakthroughs have been particularly impressive in nephrology, for which marked disparities exist in rates and etiologic classifications of end-stage kidney disease between African Americans and European Americans. Discovery of the apolipoprotein L1 gene (APOL1) association with focal segmental glomerulosclerosis, human immunodeficiency virus (HIV)-associated nephropathy, lupus nephritis, sickle cell nephropathy, and solidified glomerulosclerosis, as well as more rapid failure of transplanted kidneys from donors with APOL1 renal-risk genotypes, has improved our understanding of nondiabetic nephropathy. Environmental factors acting through natural selection in sub-Saharan African populations likely underlie this association. This article describes the discovery of chromosome 22q renal-risk variants and their worldwide distribution, reviews the epidemiology and pathology of APOL1-associated nephropathies, and explores several proposed mechanisms of kidney injury identified in cell culture and animal models. Detection of APOL1 associations with kidney diseases and delineation of injury pathways brings hope for effective treatment for these kidney diseases.

Keywords: APOL1; African Americans; African ancestry; HIV-associated nephropathy (HIVAN); apolipoprotein A1; chronic kidney disease (CKD); disparities; focal segmental glomerulosclerosis (FSGS); genetic determinants; genotype; race/ethnicity; renal risk variant; review.

PubMed Disclaimer

Figures

Figure 1:
Figure 1:
Geographic distribution of APOL1 renal risk alleles and Trypanosoma brucei subspecies. Shown are the distributions of G1 (left) and G2 (right) alleles among population groups, mostly in sub-Saharan Africa, together with the population ranges for Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense (ranges based on information from WHO). The Great Rift Valley is shown as a line running from southwest to northeast. The population numbers refer to Table 1 from Limou et al. Reproduced from Limou et al with the permission of the copyright holder, Elsevier, Inc.
See this image and copyright information in PMC

References

    1. Saran R, Robinson B, Abbott KC, et al. US Renal Data System 2016 annual data report: epidemiology of kidney disease in the United States. Am J Kidney Dis. 2017;69(3)(suppl 1):A7–A8. - PMC - PubMed
    1. Ferguson R, Grim CE, Opgenorth TJ: A familial risk of chronic renal failure among blacks on dialysis? J Clin Epidemiol 1988;41 (12): 1189–1196. - PubMed
    1. Freedman BI, Spray BJ, Tuttle AB, Buckalew VM Jr.: The familial risk of end-stage renal disease in African Americans. Am J Kidney Dis 1993;21:387–393. - PubMed
    1. Spray BJ, Atassi NG, Tuttle AB, Freedman BI: Familial risk, age at onset, and cause of end-stage renal disease in white Americans. J Am Soc Nephrol 1995;5(10):1806–1810. - PubMed
    1. Freedman BI, Wilson CH, Spray BJ, Tuttle AB, Olorenshaw IM, Kammer GM: Familial clustering of end-stage renal disease in blacks with lupus nephritis. Am J Kidney Dis 1997;29(5):729–732. - PubMed

Publication types