CFAR Awards

Michelle Estrella, MD

Nephrology, Johns Hopkins University School of Medicine

Are polymorphisms in chromosome 22, risk factors for HIVAN in South African Adults?

Michelle Estrella, MD - Image

Insights on HIV-related kidney disease among South Africans were extrapolated from findings in developed countries.  The prevalence of renal disease-related genetic and environmental factors, however, likely differs; therefore, application of findings from developed countries may be invalid.  HIV-infected South Africans present with advanced kidney disease, with limited availability of diagnostic and treatment interventions.  Therefore, strategies for identifying those at greatest risk of kidney disease are needed to inform preventive strategies in this population.  Recently discovered APOL1 risk variants associated with kidney disease among African Americans may be potentially useful in the diagnosis and management of kidney disease among HIV-infected South Africans.  The purpose of this proposal is to advance our understanding of the role of APOL1 variants in the manifestation of kidney disease among HIV-infected South Africans.  Specifically, we aim: 1) to evaluate whether APOL1 risk alleles are associated with kidney disease; 2) to determine whether APOL1 genotype is predictive of underlying renal histopathological findings; and 3) to compare APOL1 renal mRNA and apolipoprotein L1 levels among risk allele carriers versus non-carriers. To achieve these aims, we have established a multidisciplinary group of collaborators from the Schools of Medicine and Public Health, University of Michigan and Stellenbosch University in Cape Town, South Africa.  This study will provide preliminary data for larger studies in which host and viral gene interactions may be examined in more depth and in which the clinical utility of APOL1 genotyping may be evaluated prospectively.