Department of Nephrology, Medical School, University of Ioannina, 45110 Ioannina, Greece.
Division of Nephrology and Hypertension, 1st Department of Internal Medicine, AHEPA Hospital, School of Medicine, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece.
Int J Mol Sci. 2019 Jul 29;20(15):3711. doi: 10.3390/ijms20153711.
Amplification of oxidative stress is present since the early stages of chronic kidney disease (CKD), holding a key position in the pathogenesis of renal failure. Induction of renal pro-oxidant enzymes with excess generation of reactive oxygen species (ROS) and accumulation of dityrosine-containing protein products produced during oxidative stress (advanced oxidation protein products-AOPPs) have been directly linked to podocyte damage, proteinuria, and the development of focal segmental glomerulosclerosis (FSGS) as well as tubulointerstitial fibrosis. Vascular oxidative stress is considered to play a critical role in CKD progression, and ROS are potential mediators of the impaired myogenic responses of afferent renal arterioles in CKD and impaired renal autoregulation. Both oxidative stress and inflammation are CKD hallmarks. Oxidative stress promotes inflammation via formation of proinflammatory oxidized lipids or AOPPs, whereas activation of nuclear factor κB transcription factor in the pro-oxidant milieu promotes the expression of proinflammatory cytokines and recruitment of proinflammatory cells. Accumulating evidence implicates oxidative stress in various clinical models of CKD, including diabetic nephropathy, IgA nephropathy, polycystic kidney disease as well as the cardiorenal syndrome. The scope of this review is to tackle the issue of oxidative stress in CKD in a holistic manner so as to provide a future framework for potential interventions.
氧化应激的扩增存在于慢性肾脏病（CKD）的早期阶段，在肾衰竭的发病机制中起着关键作用。肾原氧化剂酶的诱导伴随着活性氧（ROS）的过度产生和氧化应激期间产生的含二酪氨酸的蛋白质产物（晚期氧化蛋白产物-AOPP）的积累，与足细胞损伤、蛋白尿以及局灶节段性肾小球硬化（FSGS）和肾小管间质纤维化直接相关。血管氧化应激被认为在 CKD 进展中起着关键作用，ROS 是 CKD 中入球小动脉的肌源性反应受损和肾自动调节受损的潜在介质。氧化应激和炎症都是 CKD 的标志。氧化应激通过形成促炎氧化脂质或 AOPP 促进炎症，而在促氧化剂环境中核因子 kappaB 转录因子的激活促进促炎细胞因子的表达和促炎细胞的募集。越来越多的证据表明氧化应激与各种 CKD 的临床模型有关，包括糖尿病肾病、IgA 肾病、多囊肾病以及心肾综合征。本综述的目的是全面解决 CKD 中的氧化应激问题，为潜在的干预措施提供未来的框架。
