Genetic Determinants of Kidney Disease in People of African Ancestry With HIV

Cardiovascular Diseases, Diabetes Mellitus, Genetic Predisposition to Disease, HIV Nephropathy, Kidney Diseases, Kidney Injury, Obesity

Black ethnicity is a major risk factor for chronic kidney disease \[CKD\] in people with HIV infection, suggesting that genetic factors are an important determinant of kidney disease progression in this population. The Gen-Africa study was established in 2018 to allow the study of genetic and clinical risk factors for CKD in people with HIV in the UK. Just over 3000 people across 15 sites were enrolled between May 2018 and January 2020. Demographic and clinical information was collected, and biological samples (buffy coats, plasma and urine) obtained. Cross-sectional analyses have revealed that participants of West-African ancestry are at higher risk of CKD and end-stage kidney disease \[ESKD\], and that genetic variants in the apolipoprotein L1 (APOL1) gene and sickle cell trait (SCT) are predictors of CKD and ESKD. The pathogenesis of APOL1- and SCT-associated CKD is incompletely understood, and additional, longitudinal data will be collected to improve understanding of the contribution of demographic, traditional CKD (diabetes, hypertension, obesity/metabolic syndrome, cardiovascular disease) and HIV (immuno-virological and hepatitis B/C co-infection status, antiretroviral medications) risk factors as well as additional genetic and epigenetic markers.

At enrolment, just over 3,000 people of (self-identified) back ethnicity provided informed consent, a blood and urine sample, weight, height, and blood pressure measurements, and completed a short questionnaire about your health issues and lifestyle factors. HIV treatment history, including most recent and nadir CD4 count and HIV viral load, viral hepatitis status and kidney function measurements were recorded. Records for about 2,350 participants have been successfully linked to the United Kingdom Collaborative HIV Cohort (UK CHIC) which has collected data (demographics, clinical and laboratory parameters) on people with HIV since 1998 at selected clinics in the United Kingdom. Several GEN-AFRICA sub-studies (CKD-AFRICA, Coronavirus disease (CoV)-AFRICA, Ob-AFRICA) have been conducted or are being planned. Each of these studies has received, or will be submitted for, regulatory approval. The studies have allowed or will allow collection of more detailed clinical information, additional biological samples, and/or through linkage with electronic clinical records, collection of longitudinal data on HIV (CD4, HIV viral load, AIDS-defining illnesses, and details of antiretroviral therapy), comorbidities (diabetes, hypertension, kidney disease, cardiovascular events), measurements such as blood pressure and weight, and results of blood tests including measures of kidney function performed as part of clinical monitoring. Data collected as part of the GEN-AFRICA study / sub-studies are stored at King's College Hospital under their GEN-AFRICA/CKD-AFRICA/CoV-AFRICA/Ob-AFRICA study identifiers (ID). Samples collected as part of these protocols are labeled by study ID and stored in the James Black Building, King's College London, London, UK, in compliance with human tissue act (HTA) standards. Prof. Frank post is the custodian of the data and samples and will be responsible for ensuring all study activity is compliant with relevant data protection and other policies.

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