Carbamylated hemoglobin and carbamylated plasma protein in hemodialyzed patients

Abstract

The carbamylation reaction in vivo involves the nonenzymatic, covalent attachment of isocyanic acid, the spontaneous dissociation product of urea, to proteins. Carbamylated proteins have been proposed as markers of uremia and indicators of uremic control. However, the utility of measuring carbamylated proteins has not been investigated adequately. Therefore, this study was done to determine the relationship between the carbamylation of long-lived protein (hemoglobin) with that of short-lived proteins (plasma proteins) in hemodialyzed patients. Significantly higher carbamylated hemoglobin (CHb; 157 +/- 40 microg valine hydantoin/g Hb) and carbamylated protein (CTP; 0.117 +/- 0.011 absorbance/mg protein) concentrations were found in hemodialyzed patients (N = 13) as compared to normal individuals (N = 9, 53 +/- 20 microg valine hydantoin/g Hb and 0.08 +/- 0.01 absorbance/mg protein, respectively). A high correlation was found between CHb and CTP concentrations (r = 0.87, P < 0.0001), demonstrating a strong relationship between these two different half-lived proteins. A six-month longitudinal study of seven hemodialyzed patients showed that the between subject correlations were significant for CHb versus CTP as well as CHb versus pre-dialysis urea. Correlations were not significant for CTP versus pre-dialysis urea or Kt/V, nor CHb versus Kt/V. Carbamylated hemoglobin fluctuated the most over this time period (30.1% +/- 20.2%), pre-dialysis urea and CTP varied less (18.3% +/- 13.4% and 14.9% +/- 7.5%, respectively), and Kt/V varied the least (6.3% +/- 3.3%). Within subject correlations were not significant between any two tests. It is unclear whether the lack of correlations found is real or a function of the small sample size. However, these data do show that CHb and CTP are positively associated and reflect the degree of urea exposure in the blood, but their usefulness for patients on maintenance hemodialysis is not clear.