Himmelfarb Jonathan
Division of Nephrology, Department of Medicine, Kidney Research Institute, University of Washington, Seattle, Washington 98104-2499, USA.
Semin Dial. 2009 Nov-Dec;22(6):636-43. doi: 10.1111/j.1525-139X.2009.00659.x.
Patients with uremia are subject to greatly increased cardiovascular risk that cannot be completely explained by traditional cardiovascular risk factors. An increase in oxidative stress and inflammation has been proposed as contributory nontraditional uremic cardiovascular risk factors. Oxidative stress reflects the balance between oxidant generation and antioxidant defense mechanisms. Reduction/oxidation (redox) reactions may result in a stochastic process leading to oxidation of neighboring macromolecules. However, in many instances the reactive oxygen species target particular amino acid residues or lipid moieties. This provides a mechanism by which increased oxidative stress and/or alteration of antioxidant mechanisms can alter cell signaling. In individuals with advanced chronic kidney disease, the redox balance is not in equilibrium and is tipped toward oxidation resulting in the dysregulation of cellular process with subsequent vascular and tissue injury. In this review, the major oxidant and antioxidant pathways and the biomarkers to assess redox status in uremia are discussed, as well as the data linking the pathogenesis of oxidative stress, inflammation, cardiovascular events, and the progressive loss of kidney function in chronic kidney disease.
尿毒症患者面临的心血管风险大幅增加，而传统心血管风险因素无法完全解释这一现象。氧化应激和炎症增加被认为是导致尿毒症心血管风险的非传统因素。氧化应激反映了氧化剂生成与抗氧化防御机制之间的平衡。还原/氧化（redox）反应可能导致一个随机过程，从而使邻近的大分子发生氧化。然而，在许多情况下，活性氧会靶向特定的氨基酸残基或脂质部分。这提供了一种机制，通过该机制，氧化应激增加和/或抗氧化机制改变可改变细胞信号传导。在晚期慢性肾病患者中，氧化还原平衡并不处于平衡状态，而是倾向于氧化，导致细胞过程失调，随后出现血管和组织损伤。在这篇综述中，我们讨论了尿毒症中主要的氧化剂和抗氧化剂途径以及评估氧化还原状态的生物标志物，以及将氧化应激、炎症、心血管事件的发病机制与慢性肾病中肾功能进行性丧失联系起来的数据。
