Abstract 18366: Clinical Modifiers of Renal Disease Progression in APOL1 Carriers in a Large Cardiovascular Cohort

Objective: Two alleles in the apoliprotein L1 ( APOL1 ) gene confer increased risk of chronic kidney disease (CKD) in African Americans. However, harboring these alleles is not sufficient to cause CKD. This study sought to examine clinical modifiers of kidney disease progression in APOL1 homozygote African Americans in a large cardiovascular cohort. Methods: We sequenced APOL1 in 1733 African Americans (by self-report) enrolled in the CATHGEN biorepository, which consists of sequential individuals referred for cardiac catheterization at Duke University Hospital from 2001-2010. The genotype distribution was: n = 1493 non-carriers and heterozygotes, and n = 240 homozygotes. Analysis, with a multivariable logistic regression model, was restricted to homozygotes with an eGFR ≥60 mL/min at baseline (64.6%, n = 155). The main outcome measure was development of incident CKD, defined as at least two subsequent eGFR < 60 separated by at least 3 months. Potential clinical modifiers examined included age, sex, hypertension, type 2 diabetes status, smoking, HDL-C, LDL-C, ejection fraction and number of diseased coronary arteries. Results: The median age for homozygotes was 55.6 years (25th/75th: 47, 64) and 56% (n = 135) were male. During follow-up, 45.3% of homozygotes with an eGFR ≥60 at baseline developed incident CKD. For individuals without type 2 diabetes on baseline, 38.8% (n = 26) developed incident CKD; 56.1% (n = 23) individuals with baseline type 2 diabetes developed incident CKD (p = 0.08). Of clinical variables examined, only presence of type 2 diabetes at baseline was a significant predictor of developing CKD (univariate odds ratio 1.7, 95% CI 1.3-2.3, p = 0.0002), and remained significant after adjusting for the other covariables (OR 2.2, 95% CI 1.4 - 3.7, p=0.001). Conclusions: A large proportion of APOL1 homozygote African Americans with preserved kidney function at baseline enrollment in a large cardiovascular study developed incident CKD. Type 2 diabetes status was the only significant independent predictor for incident CKD in these individuals. These results highlight the potential need for greater diabetes-related efforts to prevent CKD progression in African Americans already at high-risk for adverse cardiovascular outcomes.