Carbamylation of serum albumin and erythropoietin resistance in end stage kidney disease.

Abstract

BACKGROUND AND OBJECTIVES:

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.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:

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).

CONCLUSION:

Carbamylation was associated with higher erythropoietin resistance index in incident dialysis patients and a better predictor of mortality than erythropoietin resistance index.

• Authors: Sahir Kalim, Hector Tamez, Julia Wenger, Elizabeth Ankers, Caitlin A Trottier, Joseph J Deferio, Anders H Berg, S Ananth Karumanchi, Ravi I Thadhani
• Journal: Clinical journal of the American Society of Nephrology : CJASN (Clin J Am Soc Nephrol) Vol. 8 Issue 11 Pg. 1927-34 (Nov 2013) ISSN: 1555-905X [Electronic] United States
• PMID: 23970130 (Publication Type: Journal Article, Multicenter Study, Observational Study, Research Support, N.I.H., Extramural)

Chemical References

• ALB protein, human
• Biomarkers
• Carbamates
• Hematinics
• Hemoglobins
• Serum Albumin
• Erythropoietin
• Serum Albumin, Human

Topics

• Aged
• Aged, 80 and over
• Anemia (blood, diagnosis, drug therapy, mortality)
• Biomarkers (blood)
• Carbamates (blood)
• Drug Resistance
• Erythropoietin (therapeutic use)
• Female
• Hematinics (therapeutic use)
• Hemoglobins (metabolism)
• Humans
• Kidney Failure, Chronic (blood, diagnosis, mortality, therapy)
• Linear Models
• Logistic Models
• Male
• Middle Aged
• Multivariate Analysis
• Odds Ratio
• Prospective Studies
• Protein Processing, Post-Translational
• Renal Dialysis (adverse effects, mortality)
• Risk Factors
• Serum Albumin (metabolism)
• Serum Albumin, Human
• Time Factors
• United States