Addressing the global burden of chronic kidney disease through clinical and translational research

Area of Science:

• Nephrology
• Genetics
• Epidemiology

Background:

• Chronic kidney disease (CKD) affects 200 million globally, with disproportionately high rates in African Americans (AAs) and populations in Sub-Saharan Africa and Asia.
• AAs exhibit a four-fold higher risk of CKD compared to non-Hispanic whites.
• End-stage renal disease impacts over 500,000 individuals annually in Sub-Saharan Africa, leading to high mortality and significant economic burden.

Purpose of the Study:

• To investigate the role of Apolipoprotein L1 (APOL1) G1 and G2 renal risk variants in the etiology of CKD.
• To understand the genetic and biologic mechanisms underlying the increased susceptibility of Africans and AAs to CKD.
• To leverage findings from large-scale genetic studies, such as the H3Africa initiative, to inform CKD research.

Main Methods:

• A large prospective genetic study involving 8000 participants across Ethiopia, Ghana, Kenya, and Nigeria under the NIH-sponsored H3Africa initiative.
• Analysis of Apolipoprotein 1 (APOL1) G1 and G2 renal risk variants.
• Integration of data from basic research in the United States and Africa.

Main Results:

• Discovery of the role of APOL1 G1 and G2 renal risk variants in AAs.
• Potential to unravel the specific etiology of CKD in AA and other black populations.
• Identification of genetic factors contributing to CKD prevalence in African populations.

Conclusions:

• APOL1 variants are crucial in understanding CKD disparities in AAs and other black populations.
• The H3Africa study and related research offer significant insights into the genetic basis of CKD.
• Further research is needed to elucidate the complex interplay of genetics and environment in CKD pathogenesis.