Matsuyama Yukie, Terawaki Hiroyuki, Terada Tomoyoshi, Era Seiichi
Department of Physiology and Biophysics, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan.
Research Division of Dialysis and Chronic Kidney Disease, Tohoku University Graduate School of Medicine, Sendai, Japan.
Clin Exp Nephrol. 2009 Aug;13(4):308-315. doi: 10.1007/s10157-009-0161-y. Epub 2009 Apr 11.
Oxidative stress is enhanced in advanced chronic kidney disease (CKD) patients and recognized as a main contributor to cardiovascular disease. Carbonyl stress is also known to be enhanced in advanced CKD; however the precise relationship between oxidative stress and carbonyl stress is not clear. The aim of this study was to investigate potential relationships between oxidative stress, carbonyl stress, and renal function among predialysis patients with CKD.
A total of 32 predialysis CKD patients (22 male, 10 female) were divided into four groups according to their values for creatinine clearance (Ccr) (group A, > or =60 ml/min; group B, 45-59 ml/min; group C, 30-44 ml/min; group D, < or =29 ml/min). As main markers of oxidative and carbonyl stresses, the redox state of Cys-34 (free thiol group) of human serum albumin [HSA(Cys-34)-redox] and the carbonyl content of serum proteins were employed, respectively.
The values for the fraction of both reversibly oxidized HSA [f(HNA-1)] and irreversibly oxidized HSA [f(HNA-2)] significantly increased with a decrease in renal function (group A, 21.0 +/- 3.4 and 1.8 +/- 0.3%; group D, 31.1 +/- 4.1 and 2.7 +/- 0.9%, respectively). The value for carbonyl content also significantly increased with a decrease in renal function (group A, 0.7 +/- 0.1 nmol/mg protein; group D, 1.1 +/- 0.2 nmol/mg protein). There was a significant positive correlation between carbonyl content and the f(HNA-2) value, while such a correlation was not observed between carbonyl content and the f(HNA-1) value, suggesting that there is a close relationship between serum protein carbonylation and irreversible albumin thiol oxidation.
There is a close relationship between oxidative stress and carbonyl stress and these are enhanced in correlation with the level of renal dysfunction among predialysis CKD patients.
晚期慢性肾脏病（CKD）患者氧化应激增强，被认为是心血管疾病的主要促成因素。羰基应激在晚期CKD中也已知会增强；然而，氧化应激与羰基应激之间的确切关系尚不清楚。本研究的目的是调查CKD透析前患者氧化应激、羰基应激与肾功能之间的潜在关系。
根据肌酐清除率（Ccr）值将32例CKD透析前患者（22例男性，10例女性）分为四组（A组，≥60 ml/min；B组，45 - 59 ml/min；C组，30 - 44 ml/min；D组，≤29 ml/min）。分别采用人血清白蛋白[HSA（Cys-34）-氧化还原状态]的Cys-34（游离巯基）氧化还原状态和血清蛋白羰基含量作为氧化应激和羰基应激的主要标志物。
随着肾功能下降，可逆氧化型HSA [f（HNA-1）]和不可逆氧化型HSA [f（HNA-2）]的比例值均显著增加（A组分别为21.0±3.4和1.8±0.3%；D组分别为31.1±4.1和2.7±0.9%）。羰基含量值也随着肾功能下降而显著增加（A组为0.7±0.1 nmol/mg蛋白；D组为1.1±0.2 nmol/mg蛋白）。羰基含量与f（HNA-2）值之间存在显著正相关，而羰基含量与f（HNA-1）值之间未观察到这种相关性，表明血清蛋白羰基化与不可逆白蛋白巯基氧化之间存在密切关系。
氧化应激与羰基应激之间存在密切关系，且在CKD透析前患者中，这些应激与肾功能障碍程度相关增强。
