Minireviews
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Nephrol. May 6, 2015; 4(2): 295-306
Published online May 6, 2015. doi: 10.5527/wjn.v4.i2.295
African origins and chronic kidney disease susceptibility in the human immunodeficiency virus era
Alex N Kasembeli, Raquel Duarte, Michèle Ramsay, Saraladevi Naicker
Alex N Kasembeli, Raquel Duarte, Saraladevi Naicker, Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa
Michèle Ramsay, Division of Human Genetics, National Health Laboratory Service and School of Pathology, Faculty of Health Sciences and the Sydney Brenner Institute for Molecular Bioscience, University of the Witwatersrand, Johannesburg 2193, South Africa
Saraladevi Naicker, Division of Nephrology, University of the Witwatersrand, Johannesburg 2193, South Africa
Author contributions: Kasembeli AN, Duarte R, Ramsay M and Naicker S planned the review, wrote specific sections and reviewed the paper; Kasembeli AN was responsible for producing the first complete draft.
Supported by NIH Fogarty International Center Grant, No. 1D43TW008330-01A1; Millennium Promise Award, Non-communicable Chronic Diseases Leadership Training Program, NHLS Research Trust, Division of Nephrology Research Fund, University of the Witwatersrand, Johannesburg and FRC Individual grant, University of the Witwatersrand, Johannesburg.
Conflict-of-interest: None.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Saraladevi Naicker, Professor, Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa. saraladevi.naicker@wits.ac.za
Telephone: +27-11-7172129 Fax: +27-11-6438777
Received: July 9, 2014
Peer-review started: July 10, 2014
First decision: October 27, 2014
Revised: January 6, 2015
Accepted: January 18, 2015
Article in press: January 20, 2015
Published online: May 6, 2015
Abstract

Chronic kidney disease (CKD) is a major public health problem worldwide with the estimated incidence growing by approximately 6% annually. There are striking ethnic differences in the prevalence of CKD such that, in the United States, African Americans have the highest prevalence of CKD, four times the incidence of end stage renal disease when compared to Americans of European ancestry suggestive of genetic predisposition. Diabetes mellitus, hypertension and human immunodeficiency virus (HIV) infection are the major causes of CKD. HIV-associated nephropathy (HIVAN) is an irreversible form of CKD with considerable morbidity and mortality and is present predominantly in people of African ancestry. The APOL1 G1 and G2 alleles were more strongly associated with the risk for CKD than the previously examined MYH9 E1 risk haplotype in individuals of African ancestry. A strong association was reported in HIVAN, suggesting that 50% of African Americans with two APOL1 risk alleles, if untreated, would develop HIVAN. However these two variants are not enough to cause disease. The prevailing belief is that modifying factors or second hits (including genetic hits) underlie the pathogenesis of kidney disease. This work reviews the history of genetic susceptibility of CKD and outlines current theories regarding the role for APOL1 in CKD in the HIV era.

Keywords: Chronic kidney disease, Genetics, African ancestry, Human immunodeficiency virus, APOL1, MYH9, Human immunodeficiency virus-associated nephropathy

Core tip: There are striking ethnic differences in the prevalence of chronic kidney disease, including human immunodeficiency virus (HIV)-associated nephropathy (HIVAN), in people of African ancestry suggestive of genetic predisposition. The APOL1 G1 and G2 alleles are more strongly associated with the risk for HIVAN than the previously reported MYH9 E1 risk haplotype in individuals of African ancestry. The high prevalence of HIVAN among individuals of African ancestry could be a result of high frequencies of APOL1 risk variants as well as the prevalence of HIV-1 subtypes and modifying factors or second hits underlying the pathogenesis of kidney disease.