Protein carbamylation predicts mortality in ESRD

Area of Science:

• Nephrology
• Cardiology
• Biochemistry

Background:

• Traditional cardiovascular risk factors inadequately explain high mortality in end-stage renal disease (ESRD).
• Protein carbamylation, driven by cyanate, post-translationally modifies proteins, promoting atherosclerosis.
• Protein-bound homocitrulline (PBHCit) indicates carbamylation and predicts cardiac events in non-ESRD populations.

Purpose of the Study:

• To investigate the association between serum PBHCit levels and mortality in ESRD patients undergoing maintenance hemodialysis.
• To determine if PBHCit can serve as a predictor of cardiovascular risk in ESRD.

Main Methods:

• Serum PBHCit levels were quantified in 347 hemodialysis patients.
• Kaplan-Meier analyses and multivariable Cox regression were used to assess the association with death over 5 years.
• Model performance was evaluated using the net reclassification index.

Main Results:

• Elevated serum PBHCit was significantly associated with increased mortality (log-rank P<0.01).
• Patients in the highest PBHCit tertile had more than double the risk of death compared to the lowest/middle tertiles (adjusted HRs ~2.3-2.4).
• Inclusion of PBHCit significantly improved the predictive multivariable model (net reclassification index 14%, P<0.01).

Conclusions:

• Serum PBHCit is a significant predictor of mortality in ESRD patients on hemodialysis.
• PBHCit levels reflect protein carbamylation and link uremia, inflammation, and atherosclerosis.
• PBHCit offers a novel biomarker for cardiovascular risk stratification in ESRD.