Oxidative stress in end-stage renal disease: an emerging threat to patient outcome
Oxidative stress in end-stage renal disease: an emerging threat to patient outcome
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DOI：
10.1093/ndt/gfg074
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发表时间：
2003-07-01
影响因子：
6.1
通讯作者：
Zoccali, C
中科院分区：
文献类型：
--
作者：
Locatelli, F;Canaud, B;Zoccali, C
导论.受终末期肾病（ESRD）影响的患者由于心血管疾病（CVD）而经历过度的发病率和死亡率，这不能。可以用经典的CVD危险因素来解释。在新出现的CVD危险因素中，氧化应激目前正受到重视。我们在终末期肾病患者氧化应激相关的关键点上达成了共识。由于抗氧化系统降低（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、透析膜和溶液的生物不相容性），ESRD患者的氧化应激增强。氧化应激和炎症密切相关，因为吞噬细胞响应炎症刺激产生不同的氧化剂自由基：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和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。考虑到自由基的半衰期非常短（秒），氧化应激的临床评估基于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和蛋白质产物、核酸氧化衍生物）或针对氧化表位的抗体（如抗氧化低密度脂蛋白抗体）的测量。同时，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、阴性炎症蛋白）均可进行评价。然而，许多评估各种氧化应激组分的实验室方法仍然需要标准化。此外，仍然不确定是否更好地测量这些组分的血浆和/或细胞内浓度或活性。通过旨在减少氧化应激的治疗干预措施（例如通过补充维生素C或维生素E）改善患者结局的可能性目前处于前列，但迄今为止的结果仍不确定。重要的是要考虑氧化应激作为一个潜在的重要来源的患者发病率和死亡率，虽然这方面的知识还没有立即适用于临床竞技场。需要进一步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，为临床实践提供循证建议。
Introduction. 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.Methods. We achieved a consensus on key points relating to oxidative stress in ESRD patients.Results. 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 interrelated, 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 antioxidants (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.Conclusions. 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.