Abstract: TH-OR41
Metabolomics Study of APOL1-Associated CKD Progression
Session Information
- CKD: Novel Risk Factors and Consequences
October 24, 2024 | Location: Room 24, Convention Center
Abstract Time: 05:10 PM - 05:20 PM
Category: CKD (Non-Dialysis)
- 2301 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention
Authors
- Zhang, Ruiyuan, Tulane University, New Orleans, Louisiana, United States
- Kelly, Tanika, University of Illinois Chicago College of Medicine, Chicago, Illinois, United States
- Grams, Morgan, New York University Grossman School of Medicine, New York, New York, United States
- Chen, Jing, Tulane University, New Orleans, Louisiana, United States
- He, Jiang, Tulane University, New Orleans, Louisiana, United States
- Li, Changwei, Tulane University, New Orleans, Louisiana, United States
Background
The apolipoprotein L1 (APOL1) gene risk variants are a major cause for chronic kidney disease (CKD) and its progression in African Americans (AA). Identifying factors that can modify the genetic risk holds great promise for personalized prevention of CKD progression. However, such factors have not been well studied. We aimed to identify urinary metabolites modifying the risk of APOL1 associated CKD progression in AA patients of the Chronic Renal Insufficiency Cohort (CRIC).
Methods
By using an untargeted approach, we measured 1,350 metabolites from 24-hour urine samples collected at baseline for all 1,513 AA participants of the CRIC. CKD progression was defined as the onset of end-stage renal disease or a 50% reduction in estimated glomerular filtration rate (eGFR) during 20 years’ follow-up. We tested interactions of each metabolite with APOL1 risk variants on CKD progression using Cox proportional hazard models adjusting for age, sex, study site, smoking, drinking, body mass index, systolic blood pressure, diabetes, cardiovascular disease, urine protein creatinine ratio, and eGFR. Metabolites with a false discovery rate corrected q <0.05 were deemed significant. Genome-wide analyses were performed for significant metabolites to identify genes associated with them.
Results
Two metabolites, decadienedioic acid (C10:2-DC) and X_24728, significantly modified the effect of APOL1 risk variants on CKD progression (Figure). The APOL1 variants only increased risk for CKD progression among those with higher than median of C10:2-DC (hazard ratio [HR]= 1.63, 95% confidence interval [CI]: 1.24-2.16) but not among those with less than the median (HR=0.85; 95% CI: 0.62-1,16). Similarly, the HRs for APOL1 risk variants were 0.88 (95% CI: 0.66-1,18) and 1.87 (95% CI: 1.39-2.52) for participants with lower than and higher than median of X_24728, respectively. In genome-wide analyses, ACOT2 upstream variant rs11626972 was associated with urinary C10:2-DC (beta for the minor G allele=-0.50, P=5.04×10-35, Figure).
Conclusion
Two urinary metabolites modified the risk of APOL1 associated CKD progression.
Funding
- Other NIH Support