Novel targets of antifibrotic and anti-inflammatory treatment in CKD.
Novel targets of antifibrotic and anti-inflammatory treatment in CKD.
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DOI：
10.1038/nrneph.2014.31
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发表时间：
2014-05
期刊：
影响因子：
--
通讯作者：
Sharma K
中科院分区：
文献类型：
--
作者：
Declèves AE;Sharma K
慢性肾脏疾病(CKD)正在成为一种世界性流行病，主要是由糖尿病和肥胖症患病率的急剧上升推动的。因此，迫切需要治疗慢性肾脏病的新靶点和治疗方法--既减轻普通人群中这种疾病的负担，又减少个别患者接受肾脏替代治疗的必要性。这篇综述强调了对慢性肾脏病发病机制的新见解，以及可能促进慢性肾脏病疾病控制疗法发展的方法。特别关注使用针对转化生长因子β超家族的抗纤维化药物的治疗方法。此外，我们还讨论了血管钙化、NADPH氧化酶家族和炎症在慢性肾脏病发病机制中的作用。我们还强调了关于肾脏能量感应通路(AMPK、sirtuins和mTOR)在各种肾脏疾病中的新理解，以及它们与炎症和纤维化的联系。最后，对线粒体功能和线粒体生物发生在进行性肾脏疾病中的作用有了令人兴奋的新见解。基于这些发现的前瞻性治疗有望在不久的将来为临床医生和患者带来新的希望。
Chronic kidney disease (CKD) is becoming a worldwide epidemic, driven largely by the dramatic rise in the prevalence of diabetes and obesity. Novel targets and treatments for CKD are, therefore, desperately needed—to both mitigate the burden of this disease in the general population and reduce the necessity for renal replacement therapy in individual patients. This Review highlights new insights into the mechanisms that contribute to CKD, and approaches that might facilitate the development of disease-arresting therapies for CKD. Particular focus is given to therapeutic approaches using antifibrotic agents that target the transforming growth factor β superfamily. In addition, we discuss new insights regarding the roles of vascular calcification, the NADPH oxidase family, and inflammation in the pathogenesis of CKD. We also highlight a new understanding regarding kidney energy sensing pathways (AMPK, sirtuins, and mTOR) in a variety of kidney diseases and how they are linked to inflammation and fibrosis. Finally, exciting new insights have been made into the role of mitochondrial function and mitochondrial biogenesis in relation to progressive kidney disease. Prospective therapeutics based on these findings will hopefully renew hope for clinicians and patients in the near future.
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