Understanding the molecular basis of APOL1-mediated kidney disease: a single-cell spatial approach

People of recent African ancestry are disproportionately affected by kidney diseases, in particular, focal segmental glomerulosclerosis (FSGS). If left untreated, affected individuals progress to kidney failure, requiring dialysis or kidney transplantation. This disparity is partly due to two risk variants of the apolipoprotein L1 (APOL1) gene, termed G1 and G2, found at high frequency in Africans and their diaspora. These risk variants are associated with different measures of kidney dysfunction in FSGS with implications for treatment. However, the molecular mechanisms that underpin these outcomes are unknown. To unravel the molecular basis of the distinct clinical outcomes in FSGS, I will use cutting-edge spatially resolved ‘omics’ technologies to determine the transcriptomic and proteomic signatures that characterise glomerular damage at the single-cell level in human kidney biopsies with different APOL1 genotypes. This project will advance our understanding of APOL1-mediated FSGS. Understanding the molecular mechanisms of APOL1-mediated FSGS is a crucial first step for developing advances in diagnosis, treatment, and overall disease management and will elicit a paradigm shift in our comprehension of kidney pathology in this underserved population.