Protein carbamylation is associated with increased mortality and CKD progression in patients with CKD: results from the EQUAL study.

Background and hypothesis: Urea accumulated in CKD patients' blood can spontaneously decompose into reactive isocyanate and bind to plasma proteins in a reaction called carbamylation. Recent studies suggest a direct link between protein carbamylation and the pathogenesis of cardiovascular events and mortality in dialysis patients. We investigated whether carbamylation of albumin (C-Alb) is associated with increased mortality, major adverse cardiovascular events, and need for dialysis in older patients with advanced CKD. Methods: The European Quality Study (EQUAL) is a multicentre prospective cohort study. CKD patients aged 65 or older with advanced CKD (eGFR ≤20 ml/min/1.73 m²) not on kidney replacement therapy were followed up for 5 years. In a subgroup of 1117 patients, C-Alb was measured at baseline using combined liquid chromatography and mass spectrometry. Multivariable analyses were adjusted for important confounders. Results: Mean C-Alb was 13.5 ± 6.5 mmol/mol. Men had higher C-Alb values than women, as well as patients with chronic heart failure compared to patients without. C-Alb correlated positively with age, creatinine, urea, and negatively with eGFR, but not with total albumin. Each unit increase of log-transformed C-Alb was associated with increased risk of overall mortality (adj. HR 1.92, 95%CI 1.40-2.64) and start of dialysis therapy (adj. HR 1.59, 95%CI 1.21-2.09). Conclusion: In older advanced CKD patients not on dialysis, increased levels of C-Alb were associated with higher mortality and need for dialysis.