Apol1 genotyping and proteinuric kidney disease in europe

Abstract Background and Aims Apolipoprotein L1 (APOL1) toxic gain-of-function variants (G1 or G2) are genetic factors driving a broad spectrum of progressive, proteinuric nephropathies referred to as APOL1-mediated kidney disease (AMKD). APOL1 genotyping is not routinely performed in kidney disease care, and prevalence of APOL1 variants among persons with chronic kidney disease (CKD) in Europe is not well known. These variants are common in persons of recent African ancestry. We report interim data of a global study estimating the prevalence of APOL1 genotypes in participants of recent African ancestry and proteinuric CKD, with a focus on data from Europe. Method Enrollment in this ongoing study will include up to 2,500 participants across different geographies who are of recent African ancestry and have focal segmental glomerulosclerosis (FSGS) or other proteinuric nondiabetic kidney disease (NDKD). The study includes a single visit during which blood samples are collected from participants to determine their APOL1 genotype using a validated polymerase chain reaction (PCR)-based assay. The percent of participants with two APOL1 variants and percent of participants in each genotype category (e.g., G1/G1, G1/G2, G2/G2) are assessed; genetic counseling services are available to participants, if desired. Results This interim analysis included 1,256 participants of whom 174 (13.9%) were from Europe. As shown in the table, among the 88 participants with FSGS and 86 participants with proteinuric NDKD, 54 (61.4%) and 32 (37.2%) have two APOL1 variants, respectively. Conclusion Our study will generate one of the largest global APOL1 genotyping data sets in participants with proteinuric kidney disease. These data begin to address a critical knowledge gap and highlight the importance of APOL1 genotyping in kidney disease care to identify AMKD, potentially optimize disease management, and enable referral for interventional clinical trials evaluating targeted therapies for AMKD.