Locatelli Francesco, Canaud Bernard, Eckardt Kai-Uwe, Stenvinkel Peter, Wanner Christoph, Zoccali Carmine
Department of Nephrology and Dialysis, Azienda Ospedale di Lecco, Ospedale A. Manzoni, Italy.
Nephrol Dial Transplant. 2003 Jul;18(7):1272-80. doi: 10.1093/ndt/gfg074.
Patients affected by end-stage renal disease (ESRD) experience an excess of morbidity and mortality due to cardiovascular disease (CVD), which cannot be fully explained by the classical CVD risk factors. Among emerging CVD risk factors, oxidative stress is currently being given emphasis.
We achieved a consensus on key points relating to oxidative stress in ESRD patients.
ESRD patients are subjected to enhanced oxidative stress, as a result of reduced anti-oxidant systems (vitamin C and selenium deficiency, reduced intracellular levels of vitamin E, reduced activity of the glutathione system) and increased pro-oxidant activity (advanced age, high frequency of diabetes, chronic inflammatory state, uraemic syndrome, bio-incompatibility of dialysis membranes and solutions). Oxidative stress and inflammation are deeply inter-related, as different oxidant free radicals are generated by phagocytic cells in response to inflammatory stimuli: both are related to endothelial dysfunction, as the endothelium is a source and a target of oxidants and participates in the inflammatory response. There is growing evidence, from experimental and clinical studies, that oxidative stress may be implicated in the pathogenesis of atherosclerosis and other complications of ESRD, namely dialysis-related amyloidosis, malnutrition and anaemia. Given that free radicals have very short half-lives (seconds), the clinical assessment of oxidative stress is based on the measurement of different stable oxidized compounds (such as lipid peroxidation products, advanced glycation and oxidation lipid and protein products, nucleic acid oxidation derivatives) or antibodies directed against oxidized epitopes (such as anti-oxidized low-density lipoprotein antibodies). At the same time, both enzymatic anti-oxidants (superoxide dismutase, catalase, glutathione peroxidase) and non-enzymatic anti-oxidants (glutathione, vitamin C, vitamin E, negative inflammatory proteins) can be evaluated. However, many laboratory methods assessing various oxidative stress components still have to be standardized. Moreover, it is still uncertain whether it is better measuring plasma and/or intracellular concentrations or activities of these components. The possibility of improving patient outcome by therapeutic interventions aimed at reducing oxidative stress, e.g. by vitamin C or vitamin E supplementation, currently is to the fore, but results so far have remained inconclusive.
It is important to consider oxidative stress as a potentially important source of patient morbidity and mortality, although this knowledge is not yet immediately applicable in the clinical arena. Further well-designed, randomized controlled clinical trials with anti-oxidants (e.g. vitamin E, vitamin C, N-acetyl cysteine, L-arginine) are required to establish evidence-based recommendations for clinical practice.
终末期肾病（ESRD）患者因心血管疾病（CVD）导致发病率和死亡率过高，而经典的CVD危险因素无法完全解释这一现象。在新出现的CVD危险因素中，氧化应激目前受到了重视。
我们就ESRD患者氧化应激的关键点达成了共识。
ESRD患者由于抗氧化系统减弱（维生素C和硒缺乏、细胞内维生素E水平降低、谷胱甘肽系统活性降低）和促氧化活性增加（高龄、糖尿病高发、慢性炎症状态、尿毒症综合征、透析膜和透析液的生物不相容性）而遭受增强的氧化应激。氧化应激和炎症密切相关，因为吞噬细胞在炎症刺激下会产生不同的氧化自由基：两者都与内皮功能障碍有关，因为内皮是氧化剂的来源和靶点，并参与炎症反应。越来越多的实验和临床研究证据表明，氧化应激可能与动脉粥样硬化及ESRD的其他并发症（即透析相关淀粉样变性、营养不良和贫血）的发病机制有关。鉴于自由基的半衰期非常短（以秒计），氧化应激的临床评估基于对不同稳定氧化化合物（如脂质过氧化产物、晚期糖基化和氧化脂质及蛋白质产物、核酸氧化衍生物）的测量或针对氧化表位的抗体（如抗氧化低密度脂蛋白抗体）。同时，可以评估酶促抗氧化剂（超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶）和非酶促抗氧化剂（谷胱甘肽、维生素C、维生素E、负性炎症蛋白）。然而，许多评估各种氧化应激成分的实验室方法仍需标准化。此外，测量这些成分的血浆和/或细胞内浓度或活性哪种更好仍不确定。目前，通过旨在降低氧化应激的治疗干预措施（如补充维生素C或维生素E）改善患者预后的可能性备受关注，但迄今为止结果仍无定论。
将氧化应激视为患者发病和死亡的潜在重要来源很重要，尽管这一知识尚未立即应用于临床领域。需要进一步进行设计良好的抗氧化剂（如维生素E、维生素C、N-乙酰半胱氨酸、L-精氨酸）随机对照临床试验，以建立基于证据的临床实践建议。
