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氧化剂/炎症在慢性肾脏病及正常衰老过程中肾功能减退中的作用

Role of oxidants/inflammation in declining renal function in chronic kidney disease and normal aging.

作者信息

Vlassara Helen, Torreggiani Massimo, Post James B, Zheng Feng, Uribarri Jaime, Striker Gary E

机构信息

Division of Diabetes and Aging, Department of Geriatrics, Mount Sinai School of Medicine, New York, New York 10029, USA.

出版信息

Kidney Int Suppl. 2009 Dec(114):S3-11. doi: 10.1038/ki.2009.401.

Abstract

Oxidant stress (OS) and inflammation increase in normal aging and in chronic kidney disease (CKD), as observed in human and animal studies. In cross-sectional studies of the US population, these changes are associated with a decrease in renal function, which is exhibited by a significant proportion of the population. However, since many normal adults have intact renal function, and longitudinal studies show that some persons maintain normal renal function with age, the link between OS, inflammation, and renal decline is not clear. In aging mice, greater oxidant intake is associated with increased age-related CKD and mortality, which suggests that interventions that reduce OS and inflammation may be beneficial for older individuals. Both OS and inflammation can be readily lowered in normal subjects and patients with CKD stage 3-4 by a simple dietary modification that lowers intake and results in reduced serum and tissue levels of advanced glycation end products. Diabetic patients, including those with microalbuminuria, have a decreased ability to metabolize and excrete oxidants prior to observable changes in serum creatinine. Thus, OS and inflammation may occur in the diabetic kidney at an early time. We review the evidence that oxidants in the diet directly lead to increased serum levels of OS and inflammatory mediators in normal aging and in CKD. We also discuss a simple dietary intervention that helps reduce OS and inflammation, an important and achievable therapeutic goal for patients with CKD and aging individuals with reduced renal function.

摘要

正如在人类和动物研究中所观察到的,氧化应激(OS)和炎症反应在正常衰老以及慢性肾脏病(CKD)过程中会增加。在美国人群的横断面研究中,这些变化与肾功能下降相关,相当一部分人群都表现出这种情况。然而,由于许多正常成年人肾功能完好,并且纵向研究表明一些人随着年龄增长仍能维持正常肾功能,所以OS、炎症与肾功能衰退之间的联系尚不清楚。在衰老小鼠中,更多的氧化剂摄入与年龄相关的CKD增加及死亡率上升有关,这表明减少OS和炎症的干预措施可能对老年人有益。通过简单的饮食调整降低摄入量并导致血清和组织中晚期糖基化终产物水平降低,正常受试者和CKD 3 - 4期患者的OS和炎症都可以很容易地得到降低。糖尿病患者,包括那些有微量白蛋白尿的患者,在血清肌酐出现可观察到的变化之前,其代谢和排泄氧化剂的能力就已经下降。因此,糖尿病肾脏可能在早期就出现OS和炎症。我们综述了饮食中的氧化剂直接导致正常衰老和CKD患者血清中OS水平及炎症介质增加的证据。我们还讨论了一种有助于减少OS和炎症的简单饮食干预措施,这对于CKD患者和肾功能减退的老年人来说是一个重要且可实现的治疗目标。

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