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Review
. 2015 May 6;4(2):295-306.
doi: 10.5527/wjn.v4.i2.295.

African origins and chronic kidney disease susceptibility in the human immunodeficiency virus era

Alex N Kasembeli  1 , Raquel Duarte  1 , Michèle Ramsay  1 , Saraladevi Naicker  1
Affiliations
Review

African origins and chronic kidney disease susceptibility in the human immunodeficiency virus era

Alex N Kasembeli et al. World J Nephrol. .

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: APOL1; African ancestry; Chronic kidney disease; Genetics; Human immunodeficiency virus; Human immunodeficiency virus-associated nephropathy; MYH9.

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Figures

Figure 1
Figure 1
Historical timeline reflecting the discovery of genetic association to chronic kidney disease in populations with African ancestry. 1Adapted from Kopp et al[31] and Kao et al[30]; 2Adapted from Freedman et al[49], Genovese et al[13], Tzur et al[29]; 3Adapted from Genovese et al[84]; 4Adapted from Kasembeli et al (2014 unpublished observations); 5Adapted from Freedman et al[64]; 6Adapted from UNAIDS report on global AIDS epidemic[18]; 7Adapted from USRDS 2012 Annual Data Report. APOL1: Apolipoprotein L1; MYH9: Non-muscle myosin heavy chain 9; ART: Antiretroviral therapy; CKD: Chronic kidney disease.
Figure 2
Figure 2
Distribution of Human African Trypanosomiasis (T.b gambiense and T.b rhodesiense), MYH9 E1 and APOL1 G1 and G2 risk alleles in Africa[12,42]. The frequency of distribution of APOL1 risk variants in Africa are represented by bar charts and overlap the areas distribution of Human African Trypanosomiasis. The numbers reflect the reported cases of Trypanosomiasis from the WHO, 2010. T.b: Trypanosoma brucei.
Figure 3
Figure 3
Gene-Gene, Gene-Environment steering contribution to APOL1 associated CKD and the positive selection of APOL1 associated CKD variants as a result of Trypanosomiasis. SRA: Serum resistant associated protein; HIV: Human immunodeficiency virus; T.b: Trypanosoma brucei; APOL1: Apolipoprotein L1; MYH9: Non-muscle myosin heavy chain 9; HIVAN: Human immunodeficiency virus-associated nephropathy; FSGS: Focal segmental glomerulosclerosis; T2DM: Type 2 diabetes mellitus; ESRD: End stage renal disease; CKD: Chronic kidney disease.
See this image and copyright information in PMC

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