Assessment Of Immunopathogenic Risk Markers For Hiv Associated Nephropathy (hivan) In Ethiopia

Background: HIV-1 infected patients are at risk of developing several types of chronicrnkidney disease, of which HIV-associated nephropathy (HIVAN) is the most prevalent.rnHIVAN is typically a complication of late stage HIV infection, associated with low CD4 cellrncounts and elevated serum HIV RNA levels. HIVAN is characterized: clinically by severernproteinuria and renal failure, and pathologically by a collapsing form of focal segmentalrnglomerulosclerosis (FSGS), which rapidly progresses to end-stage renal disease (ESRD) in atrnrisk individuals. Susceptibility to ESRD among HIV-infected individual, has been attributedrnto MYH9 E-1 and APOL1 G1 and G2 genetic variation. We determined the frequency ofrnMYH9 E-1 and APOL1 G1 and G2 risk variants together with the prevalence of HIVANrnamong HIV infected individuals of Ethiopian population to determine whether the kidneyrndisease genetic risk is all African or restricted to West Africa, and can explain the previouslyrnreported low risk of HIVAN among Ethiopians.rnObjective: The objective of the study was to assess immunopathogenic risk markers for HIVAssociatedrnNephropathy in EthiopiarnMethods: We studied a cohort of 200 HIV-infected individuals (120 patients already on ARTrnand 80 ART naïve patients) who were treated in ART clinic of Tikur Anbessa TeachingrnHospital. We sought clinical evidence for HIVAN (serum creatinine > 1.4 mg/dl orrnproteinuria > 30 mg/dl at a spot urine sample). Genetic analyses include the genotyping of thernMYH9 E-1 risk haplotype and APOL1 G1 and G2 risk markers (variants). Statistical analysisrncompared clinical and genetic indices for HIV-infected individuals of Ethiopian populationrnand overall Ethiopians, in comparison to those reported for HIV-infected African Americans,rnoverall African Americans, West Africans and non-Africans.rnResults: In our study, none of the HIV-infected patients of Ethiopian populations showedrnclinical criteria for HIVAN. This absence of clinically apparent HIVAN was statisticallyrnsignificant difference from that reported for African Americans. The genetic indices showedrnthat, 56% of HIV infected individuals of Ethiopians carried the MYH9 E-1 risk haplotype.rnThis frequency of MYH9 E-1 risk haplotype is almost consistent with the frequency reportedrnfor African Americans and West Africans. The frequency of APOL1 G1 and G2 risk variantsrnixrnwere zero percent in all of the 200 HIV-infected individuals of Ethiopian population. Globalrnancestry and the frequencies of the G1 and G2 APOL1 risk variants are not statisticallyrndifferent from their frequencies in the general Ethiopian population, but are significantly andrndramatically lower than those observed among HIV-infected African Americans, overallrnAfrican Americans and West Africans.rnConclusion: Although 56% of HIV infected individuals of Ethiopian populations havernMYH9 E-1 risk haplotype and that seems consistent with the previously reported AfricanrnAmericans and West African populations risk for HIVAN, the coinciding absence of HIVANrnand the APOL1 risk variants (G1 and G2) among HIV-infected individuals of Ethiopiansrnsupport a western and west central Africa, rather than all African ancestry risk for end stagernrenal disease, and can readily explain the lack of HIVAN among individuals of Ethiopianrnpopulations.rnKeywords/phrases: HIVAN, ESRD, MYH9 E-1 risk haplotype, APOL1 G1 and G2 riskrnMarkers, Serum creatinine, Proteinuria

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