title: Longitudinal Changes in Protein Carbamylation and Mortality Risk after Initiation of Hemodialysis.
abstract: Carbamylation describes a post-translational protein modification associated with adverse outcomes in ESRD, but the risk implications of changes in carbamylation over time are not well understood.
  
  
  
  We investigated the 1-year natural history of protein carbamylation in patients initiating maintenance hemodialysis and determined the prognostic value of longitudinal carbamylation changes in relation to mortality. In a nested patient-control study, we measured serial carbamylated albumin concentrations in select participants from a large incident dialysis cohort followed from 2004 to 2005 (n=10,044); 122 individuals who survived at least 90 days but died within 1 year of initiating hemodialysis (patients) were randomly selected along with 244 individuals who survived for at least 1 year (controls; matched for demographics). Carbamylated albumin concentration was measured using plasma collected at dialysis initiation and every subsequent 90-day period until 1 year or death.
  
  
  
  Baseline carbamylated albumin concentration was similar between controls and patients (mean±SD; 18.9±0.7 and 19.8±1.1 mmol/mol, respectively;P=0.94). From dialysis initiation to day 90, carbamylated albumin concentration markedly fell in all patients, with controls -9.9±0.8 mmol/mol (P<0.001) and patients -10.0±1.2 mmol/mol (P<0.001). Adjusted repeated measures analysis of carbamylated albumin concentration from dialysis initiation to 1 year or death showed that the mean change (95% confidence interval) in carbamylated albumin concentration from baseline to final measure differed significantly between groups (-9.3; 95% confidence interval, -10.8 to -7.7 for controls and -6.3; 95% confidence interval, -7.7 to -2.8 for patients;P<0.01). There were no such between-group differences in blood urea levels, Kt/V, or normalized protein catabolic rate. Mortality prediction assessed usingcstatistics showed that carbamylated albumin concentration, when modeled continuously as the difference from baseline to final, improved a fully adjusted model from 0.76 to 0.87 (P=0.03).
  
  
  
  Protein carbamylation decreased with dialysis initiation, and a greater reduction over time was associated with a lower risk for mortality. Carbamylation changes were able to predict individuals' mortality risk beyond traditional variables, including markers of dialysis adequacy and nutrition.
authors.affiliation: Department of Medicine, Division of Nephrology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; and.
authors.forename: Sahir
authors.initials: S
authors.lastname: Kalim
authors.affiliation: Department of Medicine, Division of Nephrology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; and.
authors.forename: Caitlin A
authors.initials: CA
authors.lastname: Trottier
authors.affiliation: Department of Medicine, Division of Nephrology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; and.
authors.forename: Julia B
authors.initials: JB
authors.lastname: Wenger
authors.affiliation: Department of Medicine, Division of Nephrology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; and.
authors.forename: Josh
authors.initials: J
authors.lastname: Wibecan
authors.affiliation: Department of Medicine, Division of Nephrology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; and.
authors.forename: Rayhnuma
authors.initials: R
authors.lastname: Ahmed
authors.affiliation: Department of Medicine, Division of Nephrology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; and.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ankers
authors.affiliation: Department of Medicine, Division of Nephrology and Center for Vascular Biology Research and.
authors.forename: S Ananth
authors.initials: SA
authors.lastname: Karumanchi
authors.affiliation: Department of Medicine, Division of Nephrology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; and.
authors.forename: Ravi
authors.initials: R
authors.lastname: Thadhani
authors.affiliation: Department of Pathology, Division of Clinical Chemistry, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
authors.forename: Anders H
authors.initials: AH
authors.lastname: Berg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001806:Blood Urea Nitrogen; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000401:mortality* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011499:Protein Processing, Post-Translational; D006435:Renal Dialysis; D018570:Risk Assessment; D012709:Serum Albumin / Q000378:metabolism*; D014481:United States / Q000453:epidemiology
chemical_list: D012709:Serum Albumin
keywords: Albumins; Blood Urea Nitrogen; Case-Control Studies; Demography; ESRD; Fluid Therapy; Humans; Kidney Failure, Chronic; Protein Processing, Post-Translational; Risk; chronic hemodialysis; mortality risk; protein carbamylation; renal dialysis; urea; uremia