Abstract: TH-PO995
Urine Metabolome and CKD Progression in African American Patients
Session Information
- CKD: Epidemiology, Risk Factors, and Prevention - 1
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2301 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention
Authors
- Li, Changwei, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, United States
- Zhang, Ruiyuan, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, United States
- Grams, Morgan, New York University Grossman School of Medicine, New York, New York, United States
- Kelly, Tanika, University of Illinois System, Urbana, Illinois, United States
- Chen, Jing, Tulane University School of Medicine, New Orleans, Louisiana, United States
- He, Jiang, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, United States
Background
Urine samples of chronic kidney disease (CKD) patients may contain unique metabolite profiles for CKD progression. However, urinary metabolomic study of CKD progression, particularly among African American (AA) patients, has not been well studied. We aimed to identify novel urinary metabolites associated with CKD progression in AA participants of the Chronic Renal Insufficiency Cohort (CRIC).
Methods
Metabolites were measured from baseline 24-hour urine samples of 1,513 AA participants of the CRIC, using an untargeted approach. After quality control, 1,350 metabolites were analyzed. CKD progression was defined as the onset of end-stage renal disease or a 50% reduction in estimated glomerular filtration rate (eGFR). Associations of metabolites with CKD progression were examined by a base model adjusting for age, sex, study site, smoking, drinking, body mass index, systolic blood pressure, diabetes, cardiovascular disease, and APOL1 risk alleles, and two models sequentially adding urine protein creatinine ratio and eGFR. Metabolites with a false discovery rate corrected q <0.05 were deemed significant. For metabolites with unknown identities, we performed genome-wide analyses to identify genes associated with them.
Results
A total of 569, 287, and 14 metabolites were significantly associated with the risk of CKD progression in the three models, respectively (Figure). Among the 14 metabolites identified in the fully adjusted model, guanidinosuccinate, a uremic toxin, was most significant, with one standard deviation increase associated with 1.31 (95% confidence interval: 1.18-1.45, q=2.25×10-4) times higher risk of CKD progression. While many known metabolites were previously linked to eGFR, two metabolites, 2-amino-2-methyl-1-propanol (AMP) and N2,N6-diacetyllysine, showed novel associations with CKD progression. Moreover, unknown metabolite X-25422 showed significant associations with ASNS and ASPG, two genes involved in asparagine synthesis and metabolism.
Conclusion
We identified 14 urinary metabolites associated with CKD progression among African Americans.
Funding
- Other NIH Support