Balion C M, Draisey T F, Thibert R J
Department of Chemistry and Biochemistry, University of Windsor, Ontario, Canada.
Kidney Int. 1998 Feb;53(2):488-95. doi: 10.1046/j.1523-1755.1998.00777.x.
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.
体内的氨甲酰化反应涉及尿素的自发解离产物异氰酸与蛋白质的非酶促共价结合。氨甲酰化蛋白质已被提议作为尿毒症的标志物和尿毒症控制的指标。然而，测量氨甲酰化蛋白质的实用性尚未得到充分研究。因此，本研究旨在确定血液透析患者中长寿蛋白质（血红蛋白）的氨甲酰化与短寿蛋白质（血浆蛋白质）的氨甲酰化之间的关系。与正常个体（N = 9，分别为53±20微克乙内酰脲缬氨酸/克血红蛋白和0.08±0.01吸光度/毫克蛋白质）相比，血液透析患者（N = 13）中氨甲酰化血红蛋白（CHb；157±40微克乙内酰脲缬氨酸/克血红蛋白）和氨甲酰化蛋白质（CTP；0.117±0.011吸光度/毫克蛋白质）的浓度显著更高。发现CHb和CTP浓度之间存在高度相关性（r = 0.87，P < 0.0001），表明这两种不同半衰期的蛋白质之间存在密切关系。对7名血液透析患者进行的为期6个月的纵向研究表明，CHb与CTP以及CHb与透析前尿素之间的受试者间相关性显著。CTP与透析前尿素或Kt/V之间以及CHb与Kt/V之间的相关性不显著。在此期间，氨甲酰化血红蛋白波动最大（30.1%±20.2%），透析前尿素和CTP变化较小（分别为18.3%±13.4%和14.9%±7.5%），而Kt/V变化最小（6.3%±3.3%）。任何两项测试之间的受试者内相关性均不显著。尚不清楚所发现的缺乏相关性是真实的还是样本量小的结果。然而，这些数据确实表明CHb和CTP呈正相关，并反映了血液中尿素暴露的程度，但它们对维持性血液透析患者的实用性尚不清楚。
