Kidney Week

Abstract: FR-PO1109

A Phenome-Wide Association Study to Investigate the Role of Carbamylation in CKD: Findings from the Chronic Renal Insufficiency Cohort

Session Information

• CKD: Epidemiology, Risk Factors, and Prevention - 2
  October 25, 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

• Awwad, Aya, Harvard Medical School, Boston, Massachusetts, United States

Aya Awwad, MD

• Rhee, Eugene P., Massachusetts General Hospital, Boston, Massachusetts, United States

Eugene P. Rhee, MD

• Garimella, Pranav S., University of California San Diego Division of Nephrology-Hypertension, San Diego, California, United States

Pranav S. Garimella, MD, MPH, FASN

• Nigwekar, Sagar U., Massachusetts General Hospital, Boston, Massachusetts, United States

Sagar U. Nigwekar, MD

• Berg, Anders H., Cedars-Sinai Medical Center, Los Angeles, California, United States

Anders H. Berg, MD, PhD

• Lash, James P., Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States

James P. Lash, MD, FASN

• Tang, Mengyao, Massachusetts General Hospital, Boston, Massachusetts, United States

Mengyao Tang, MD, MPH, FASN

• Kalim, Sahir, Massachusetts General Hospital, Boston, Massachusetts, United States

Sahir Kalim, MD, MS, MSc, FASN

Background

Protein carbamylation, a urea driven post-translational protein modification, increases in patients with CKD and contributes to the excess morbidity and mortality observed in this population. Given urea’s, and thus carbamylation's, ubiquitous nature in the body, we hypothesized carbamylation would associate with a broad range of clinical phenotypes.

Methods

We evaluated the cross-sectional association of carbamylation -assessed by carbamylated albumin (C-Alb)- with 243 phenotypic correlates among 3,111 CKD participants in the Chronic Renal Insufficiency Cohort using a phenome-wide association study (PheWAS). Models were adjusted for demographics, eGFR, and proteinuria, and a conservative Bonferroni adjusted threshold for significance was applied. Results prompted a focused post-PheWAS analysis on the association between C-Alb and coronary artery calcification (CAC) measured by Agatston scores.

Results

C-Alb was significantly associated with hematological abnormalities such as anemia diagnosis (OR: 2.04; 95% CI [1.81, 2.3], adj. pvalue=2.17 × 10-28), cardiovascular abnormalities such as increased left ventricular mass (OR: 1.38; 95% CI [1.19, 1.61], adj. pvalue=5.9 × 10-3), and lipid profile among other phenotypes (Fig.1a). C-Alb’s positive association with calcification indices was the largest numerically in standardized magnitude among significant phenotypes (Fig.1b). The association with Agatston score remained significant even after adjusting for traditional atherosclerotic risk factors (β 0.77, 95% CI [0.35-1.19], pvalue <0.001).

Conclusion

Our findings showcase the wide systemic correlates of carbamylation in patients with CKD, particularly in the cardiovascular system. Carbamylation emerged as an independent risk factor for CAC, suggesting its potential as a target for therapeutic intervention to mitigate cardiovascular risk in CKD populations.

Funding

• NIDDK Support