title: Carbamylation of serum albumin and erythropoietin resistance in end stage kidney disease.
abstract: OBJECTIVE
  The mechanisms underlying erythropoietin resistance are not fully understood. Carbamylation is a post-translational protein modification that can alter the function of proteins, such as erythropoietin. The hypothesis of this study is that carbamylation burden is independently associated with erythropoietin resistance.
  
  
  METHODS
  In a nonconcurrent prospective cohort study of incident hemodialysis patients in the United States, carbamylated albumin, a surrogate of overall carbamylation burden, in 158 individuals at day 90 of dialysis initiation and erythropoietin resistance index (defined as average weekly erythropoietin dose [U] per kg body weight per hemoglobin [g/dl]) over the subsequent 90 days were measured. Linear regression was used to describe the relationship between carbamylated albumin and erythropoietin resistance index. Logistic regression characterized the relationship between erythropoietin resistance index, 1-year mortality, and carbamylation.
  
  
  RESULTS
  The median percent carbamylated albumin was 0.77% (interquartile range=0.58%-0.93%). Median erythropoietin resistance index was 18.7 units/kg per gram per deciliter (interquartile range=8.1-35.6 units/kg per gram per deciliter). Multivariable adjusted analysis showed that the highest quartile of carbamylated albumin was associated with a 72% higher erythropoietin resistance index compared with the lowest carbamylation quartile (P=0.01). Increasing erythropoietin resistance index was associated with a higher risk of death (odds ratio per unit increase in log-erythropoietin resistance index, 1.69; 95% confidence interval, 1.06 to 2.70). However, the association between erythropoietin resistance index and mortality was no longer statistically significant when carbamylation was included in the analysis (odds ratio, 1.44; 95% confidence interval, 0.87 to 2.37), with carbamylation showing the dominant association with death (odds ratio for high versus low carbamylation quartile, 4.53; 95% confidence interval, 1.20 to 17.10).
  
  
  CONCLUSIONS
  Carbamylation was associated with higher erythropoietin resistance index in incident dialysis patients and a better predictor of mortality than erythropoietin resistance index.
authors: Department of Medicine, Division of Nephrology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts;, †Department of Pathology, Division of Clinical Chemistry and, ‡Department of Medicine, Division of Nephrology and Center for Vascular Biology Research, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
authors: Sahir
authors: S
authors: Kalim
authors: Hector
authors: H
authors: Tamez
authors: Julia
authors: J
authors: Wenger
authors: Elizabeth
authors: E
authors: Ankers
authors: Caitlin A
authors: CA
authors: Trottier
authors: Joseph J
authors: JJ
authors: Deferio
authors: Anders H
authors: AH
authors: Berg
authors: S Ananth
authors: SA
authors: Karumanchi
authors: Ravi I
authors: RI
authors: Thadhani
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D015415:Biomarkers / Q000097:blood; D002219:Carbamates / Q000097:blood*; D004351:Drug Resistance; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D006397:Hematinics / Q000627:therapeutic use*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011446:Prospective Studies; D011499:Protein Processing, Post-Translational; D006435:Renal Dialysis / Q000009:adverse effects / Q000401:mortality; D012307:Risk Factors; D012709:Serum Albumin / Q000378:metabolism*; D000075462:Serum Albumin, Human; D013997:Time Factors; D014481:United States
chemical_list: C422455:ALB protein, human; D015415:Biomarkers; D002219:Carbamates; D006397:Hematinics; D006454:Hemoglobins; D012709:Serum Albumin; D004921:Erythropoietin; D000075462:Serum Albumin, Human
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