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

TL;DR

Higher levels of carbamylated albumin in older patients with advanced kidney disease are linked to increased risk of death and dialysis.

Contribution

This study shows that carbamylated albumin is a novel predictor of mortality and dialysis need in advanced CKD patients.

Findings

Carbamylated albumin levels were higher in men and patients with heart failure.

Each increase in carbamylated albumin was associated with higher mortality and dialysis risk.

Carbamylated albumin correlated with kidney function decline but not with total albumin levels.

Abstract

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.

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.

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).

In older advanced CKD patients not on dialysis, increased levels of C-Alb were associated with higher mortality and need for dialysis.

Graphical Abstract

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