APOL1 Renal Risk Variants and Sickle Cell Trait Associations With Reduced Kidney Function in a Large Congolese Population-Based Study

Author:

Masimango, Mannix Imani

Jadoul, Michel

Binns-Roemer,Elizabeth

David,Victor

Sumaili, Ernest Kiswaya

Winkler,Cheryl

Limou, Sophie
Author Address

Department of Internal Medicine, H 244;pital Provincial G 233;n 233;ral de R 233;f 233;rence de Bukavu, Universit 233; Catholique de Bukavu, Bukavu, Democratic Republic of the Congo., Department of Nephrology, Cliniques Universitaires Saint-Luc, Universit 233; Catholique de Louvain, Brussels, Belgium., Basic Science Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Leidos Biomedical Research Inc., Frederick National Laboratory, Frederick, Maryland, USA., Department of Nephrology, Universit 233; de Kinshasa, Kinshasa, Democratic Republic of the Congo., Institute for Transplantation in Urology-Nephrology, Centre de Recherche en Transplantation et Immunologie, UMR1064, Institut National de la Sant 233; et de la Recherche M 233;dicale, Universit 233; de Nantes, Nantes, France., Ecole Centrale de Nantes, Computer sciences and Mathematics in Biology Department, Nantes, France.,

Abstract:

APOL1, GSTM1 risk variants, and sickle cell trait (SCT) are associated with chronic kidney disease (CKD) among African Americans (AAs). Nevertheless, such evidence remains scarce in sub-Saharan Africa (SSA) populations. In a cross-sectional study, we evaluated the prevalence of these risk variants and their association with estimated glomerular filtration rate (eGFR), albuminuria, and CKD in urban (n = 587) and rural (n = 730) adults from South-Kivu, DR Congo (DRC). Furthermore, we evaluated APOL1 recessive model (high risk [HR] vs. low risk [LR]), SCT carriage, and the active versus inactive GSTM1 genotypes. The frequencies of the APOL1 G1 and G2 alleles were 8.7% and 9.1%, respectively, and 3.2% carried the HR genotype. SCT and GSTM1 null allele frequencies were 3.8% and 51.2%, respectively. APOL1 HR was associated with lower eGFR (P = 0.047, odds ratio [OR] = 4). Individuals with SCT exhibited lower eGFR (P = 0.018), higher albuminuria (P = 0.032), and 2.4× increased risk of CKD (P = 0.031). APOL1 HR and SCT were synergistically associated with lower eGFR (Pinteraction = 0.012). The GSTM1 null allele was not significantly associated with any renal outcomes. Our study highlighted the impact of APOL1 and SCT variants on poorer renal outcomes in the DRC and advocates for further genetic studies in SSA settings. © 2021 International Society of Nephrology. Published by Elsevier Inc.

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