Terawaki Hiroyuki, Yoshimura Kazunobu, Hasegawa Toshio, Matsuyama Yukie, Negawa Tsuneo, Yamada Kenichi, Matsushima Masato, Nakayama Masaaki, Hosoya Tatsuo, Era Seiichi
Department of Nephrology and Hypertension, Tokyo Jikei University School of Medicine, Tokyo, Japan.
Kidney Int. 2004 Nov;66(5):1988-93. doi: 10.1111/j.1523-1755.2004.00969.x.
Cardiovascular disease is known to be the most important complication among patients with renal failure, and oxidative stress has been proposed to play a major role as the source of such complications. Human serum albumin (HSA) is composed of human mercaptoalbumin (HMA) with cysteine residues having reducing powers, of reversibly oxidized human non-mercaptoalbumin-1 (HNA-1), and strongly oxidized human non-mercaptoalbumin-2 (HNA-2).
We used the "redox state of HSA" as a marker to investigate the current status of oxidative stress in predialysis patients with renal failure. The subjects were 55 nondialysis patients (31 males and 24 females) with chronic renal diseases, and having various degrees of renal function. The subjects' redox state of HSA was determined by a high-performance liquid chromatographic (HPLC) procedure, and the results presented in terms of the ratios between HNA-total(HNA-1 + HNA-2) and HNA-2.
The values for each fraction of HNA-total (f(HNA-total)) and f(HNA-2) were increased with a decrease of renal functions, and a significant positive correlation with serum creatinine (R= 0.529, P < 0.0001 and R= 0.618, P < 0.0001) was detected. Multiple (forward stepwise) regression analysis using f(HNA-total) and f(HNA-2) as the criterion variables was performed, and creatinine was adopted as significant explanatory variable in both equations.
We found that even before dialysis, oxidative stress was enhanced in correlation with the level of renal dysfunction among patients with chronic renal failure. In the future, antioxidant strategies should become part of treatment for predialysis renal failure.
众所周知,心血管疾病是肾衰竭患者最重要的并发症,氧化应激被认为是此类并发症的主要来源。人血清白蛋白(HSA)由具有还原能力的含半胱氨酸残基的人巯基白蛋白(HMA)、可逆氧化的人非巯基白蛋白-1(HNA-1)和强氧化的人非巯基白蛋白-2(HNA-2)组成。
我们以“HSA的氧化还原状态”为标志物,研究肾衰竭透析前患者氧化应激的现状。研究对象为55例患有慢性肾脏疾病、具有不同程度肾功能的非透析患者(31例男性和24例女性)。通过高效液相色谱(HPLC)法测定研究对象HSA的氧化还原状态,结果以HNA总量(HNA-1 + HNA-2)与HNA-2的比值表示。
HNA总量的各组分值(f(HNA总量))和f(HNA-2)随肾功能下降而升高,且与血清肌酐呈显著正相关(R = 0.529,P < 0.0001和R = 0.618,P < 0.0001)。以f(HNA总量)和f(HNA-2)作为标准变量进行多元(向前逐步)回归分析,肌酐在两个方程中均被用作显著解释变量。
我们发现,即使在透析前,慢性肾衰竭患者的氧化应激也会随着肾功能障碍程度的增加而增强。未来,抗氧化策略应成为透析前肾衰竭治疗的一部分。