Abstract MPTH71: Vitamin E Intake May Mitigate the Risk of APOL1 -Associated Kidney Disease Progression Among African Americans

Introduction: Carrying two high-risk alleles (G1 and G2) in the apolipoprotein L1 ( APOL1 ) gene markedly increases the risk of chronic kidney disease (CKD) and its progression. Due to evolutionary selection from Trypanosoma brucei , African Americans have a disproportionately higher prevalence of these alleles. However, only a subset of APOL1 high risk genotype carriers develop CKD or experience rapid progression, suggesting the presence of modifying factors. Vitamin E exerts antioxidant, anti-inflammatory, and endothelial-protective effects, which may counteract APOL1 -associated kidney injury. Therefore, we examined whether circulating vitamin E metabolites modify APOL1 -associated CKD progression among African Americans patients with CKD. Hypothesis: Higher circulating levels of vitamin E metabolites attenuate the risk of APOL1 -associated CKD progression among African American patients with CKD. Methods: We analyzed data from 1,513 African American participants with CKD in the Chronic Renal Insufficiency Cohort (CRIC). Plasma levels of 12 vitamin E-related metabolites were quantified using the untargeted Metabolon platform. APOL1 genotypes were classified as high-risk (two risk alleles) or low risk (0 or 1 risk alleles). CKD progression was defined as developing end-stage kidney disease or having estimated glomerular filtration rate declined by 50% in up to 20 years of follow-up. Cox proportional hazards models were used to test APOL1 -metabolite interactions while adjusting for age, sex, BMICL1 , total cholesterol, smoking, drinking, physical activity, education, diabetes, hypertension, and use of ACE inhibitors or ARBs. The 12 metabolites formed 4 independent clusters (pairwise ρ<0.5). So, a Bonferroni corrected significance threshold of P <0.0125 was applied. Results: γ-CEHC glycine significantly ( P for interaction=0.01) and α-CEHC glucuronide nominally ( P for interaction=0.04) modified the APOL1 -CKD progression association. The APOL1 high-risk genotype was associated with faster CKD progression only among those with below-median levels of γ-CEHC glycine (HR=1.88, 95% CI: 1.47 – 2.42, P<0.001CL2 ), but not among those with above-median levels (HR=1.31, 95% CI: 0.99-1.73, P=0.06). Similar patterns were observed for α-CEHC glucuronide . Conclusions: Vitamin E metabolism may represent a modifiable pathway that mitigates APOL1 -associated CKD progression among African Americans.