title: Protein carbamylation is associated with heart failure and mortality in diabetic patients with end-stage renal disease.
abstract: 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.
authors: 1] Division of Nephrology, Department of Internal Medicine, University Hospital Würzburg, Würzburg, Germany [2] Comprehensive Heart Failure Centre, University Hospital of Würzburg, Würzburg, Germany.
authors: Christiane
authors: C
authors: Drechsler
authors: Division of Nephrology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors: Sahir
authors: S
authors: Kalim
authors: Division of Nephrology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors: Julia B
authors: JB
authors: Wenger
authors: Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors: Pirianthini
authors: P
authors: Suntharalingam
authors: 1] Division of Nephrology and Center for Vascular Biology Research, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA [2] Howard Hughes Medical Institute, Boston, Massachusetts, USA.
authors: Tammy
authors: T
authors: Hod
authors: Division of Nephrology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors: Ravi I
authors: RI
authors: Thadhani
authors: 1] Division of Nephrology and Center for Vascular Biology Research, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA [2] Howard Hughes Medical Institute, Boston, Massachusetts, USA.
authors: S Ananth
authors: SA
authors: Karumanchi
authors: 1] Division of Nephrology, Department of Internal Medicine, University Hospital Würzburg, Würzburg, Germany [2] Comprehensive Heart Failure Centre, University Hospital of Würzburg, Würzburg, Germany.
authors: Christoph
authors: C
authors: Wanner
authors: Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors: Anders H
authors: AH
authors: Berg
mesh_terms: D000368:Aged; D000069059:Atorvastatin / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000097:blood / Q000401:mortality; D002423:Cause of Death; D002784:Cholesterol / Q000097:blood; D015897:Comorbidity; D016757:Death, Sudden, Cardiac / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000401:mortality*; D003928:Diabetic Nephropathies / Q000097:blood / Q000401:mortality* / Q000628:therapy; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000401:mortality*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006973:Hypertension / Q000097:blood / Q000401:mortality; D007676:Kidney Failure, Chronic / Q000097:blood / Q000401:mortality* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D006435:Renal Dialysis / Q000009:adverse effects / Q000706:statistics & numerical data; D012307:Risk Factors; D012709:Serum Albumin / Q000378:metabolism*; D015996:Survival Rate; D020107:Troponin T / Q000097:blood; D014511:Uremia / Q000097:blood
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010446:Peptide Fragments; D012709:Serum Albumin; D020107:Troponin T; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D002784:Cholesterol; D000069059:Atorvastatin