Protein carbamylation is associated with heart failure and mortality in diabetic patients with end-stage renal disease

Kidney Int. 2015 Jun;87(6):1201-8. doi: 10.1038/ki.2014.429. Epub 2015 Feb 11.


Serum carbamylated albumin (C-Alb) levels are associated with excess mortality in patients with diabetic end-stage renal disease. To gain insight into the pathophysiology of carbamylation, we determined associations between C-Alb and causes of death in patients on chronic hemodialysis. The Die Deutsche Diabetes Dialyse Studie (4D study) was a randomized controlled trial testing the effects of atorvastatin on survival in diabetic patients on dialysis during a median follow-up of 4 years. We stratified 1161 patients by C-Alb to see whether differences in carbamylation altered the effects of atorvastatin on survival. Baseline C-Alb significantly correlated with serum cardiac stress markers troponin T and N-terminal pro-B-type-natriuretic peptide and was associated with a history of heart failure and arrhythmia. C-Alb was strongly associated with 1-year adjusted risk of cardiovascular mortality, sudden cardiac death, and the 4-year risk of death from congestive heart failure (hazard ratios of 3.06, 3.78, and 4.64, respectively) but not with myocardial infarction or stroke. Patients with low C-Alb, treated with atorvastatin, experienced a significant improvement in their 4-year survival (hazard ratio 0.692). High C-Alb levels are associated with ongoing cardiac damage, risk of congestive heart failure, and sudden cardiac death. Thus, carbamylation and uremic cardiomyopathy are associated in patients with diabetes mellitus and kidney disease. In addition, statins were specifically beneficial to hemodialysis patients with low C-Alb.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Atorvastatin / therapeutic use*
  • Atrial Fibrillation / blood
  • Atrial Fibrillation / mortality
  • Cause of Death
  • Cholesterol / blood
  • Comorbidity
  • Death, Sudden, Cardiac / epidemiology
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / mortality*
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / mortality*
  • Diabetic Nephropathies / therapy
  • Female
  • Heart Failure / blood
  • Heart Failure / mortality*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hypertension / blood
  • Hypertension / mortality
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / mortality*
  • Kidney Failure, Chronic / therapy
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Peptide Fragments / blood
  • Renal Dialysis / adverse effects
  • Renal Dialysis / statistics & numerical data
  • Risk Factors
  • Serum Albumin / metabolism*
  • Survival Rate
  • Troponin T / blood
  • Uremia / blood


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Peptide Fragments
  • Serum Albumin
  • Troponin T
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Cholesterol
  • Atorvastatin