Abstract: TH-PO1075
Prognostic Comparisons of Carbamylated Albumin and Homocitrulline-Two Circulating Markers of Protein Carbamylation in CKD
Session Information
- CKD Progression and Complications: Diagnosis, Prognosis, Risk Factors
November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials
Authors
- Awwad, Aya, Harvard Medical School, Boston, Massachusetts, United States
- Rhee, Eugene P., Massachusetts General Hospital, Boston, Massachusetts, United States
- Grams, Morgan, New York University, New York, New York, United States
- Rincon-Choles, Hernan, Cleveland Clinic, Cleveland, Ohio, United States
- Sondheimer, James H., Wayne State University, Detroit, Michigan, United States
- He, Jiang, Tulane University, New Orleans, Louisiana, United States
- Chen, Jing, Tulane University, New Orleans, Louisiana, United States
- Hsu, Chi-yuan, University of California San Francisco, San Francisco, California, United States
- Ramachandran, Vasan S., Boston University, Boston, Massachusetts, United States
- Kimmel, Paul L., National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States
- Berg, Anders H., Cedars-Sinai Medical Center, Los Angeles, California, United States
- Lash, James P., University of Illinois Chicago, Chicago, Illinois, United States
- Tang, Mengyao, Massachusetts General Hospital, Boston, Massachusetts, United States
- Kalim, Sahir, Massachusetts General Hospital, Boston, Massachusetts, United States
Background
Protein carbamylation, a urea driven post-translational protein modification, associates with adverse outcomes in CKD. Circulating markers of carbamylation include carbamylated albumin (C-Alb) and homocitrulline (HCit, carbamylated lysine), but prognostic comparisons between the 2 have never been made. Demonstrating comparability of the 2 markers could facilitate study comparisons and support HCit use from existing databases (HCit is a common analyte on metabolomic platforms). We thus compared the prognostic performance of C-Alb and HCit in a prospective CKD cohort.
Methods
Baseline C-Alb and HCit levels were assayed using mass spectrometry (Broad Institute Metabolomics Platform for HCit) in 1659 patients with CKD stages 2-4 enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study. We compared associations to the endpoints of death and end stage kidney disease (ESKD). Adjusted Cox proportional hazard models (including eGFR and proteinuria) and C-statistics were used to compare the prognostic performance of each marker.
Results
Participant demographics included mean (SD) age 57 (10.7) years; 712 (42.9%) females; 704 (42.4%) White. Participants in the highest quartile across the two-biomarkers had similar baseline characteristics (e.g., serum urea nitrogen for HCit was 45 [35-58] mg/dL, for C-Alb 44 [34-58] mg/dL). The 2 markers showed a correlation coefficient of 0.64, P<.001, (HCit was the strongest correlate to C-Alb amongst >400 analytes from the Broad platform). In multivariable adjusted Cox models, on a continuous scale or in quartiles, HCit and C-Alb showed similar increase in the risk of either death or ESKD with increasing risk observed at higher levels (HR for death in 4th quartile compared to the 1st was1.86 (95% confidence interval [CI]:1.26-2.77) for HCit, and 1.90 (1.36-2.65) for C-Alb. The top quartile of both biomarkers had a similar but distinct HRs for ESKD with overlapping CIs. Measures of model performance showed significant and identical improvements when each carbamylation biomarker was added to fully adjusted models.
Conclusion
HCit was similar to C-Alb across multiple prognostic assessments, thus may have potential to be utilized like C-Alb in CKD clinical outcomes studies.
Funding
- NIDDK Support