{"title":"Role of Inflammation in Progression of Chronic Kidney Disease in Type 2 Diabetes Mellitus: Clinical Implications","authors":"Yasuhiro Oda MD, Hiroshi Nishi MD, PhD, Masaomi Nangaku MD, PhD","doi":"10.1016/j.semnephrol.2023.151431","DOIUrl":null,"url":null,"abstract":"<div><p><span><span>Progression of chronic kidney disease<span> in type 2 diabetes has been understood conventionally as a consequence of intraglomerular hemodynamic changes and aberrant metabolic pathways. However, an increasing body of experimental evidence has highlighted the role of inflammatory response in the progression of </span></span>diabetic kidney disease<span><span><span><span>. Macrophage polarization in response to specific microenvironmental stimuli affects the pathology of diabetic kidneys. The diabetic milieu also up-regulates </span>inflammatory cytokines, </span>chemokines, and </span>adhesion molecules<span>, and promotes inflammatory signal transduction pathways<span><span>, including inflammasomes. Therefore, from a reverse translational perspective, modulation of the inflammatory response may be the driving force of the renoprotective effects of renin-angiotensin system inhibitors, sodium-glucose cotransporter-2 inhibitors, and </span>mineralocorticoid receptor antagonists<span>, all of which have been shown to slow disease progression. Currently, many agents that target the inflammation in the kidneys directly are evaluated in </span></span></span></span></span>clinical trials<span>. This article discusses recent clinical and experimental milestones in drug development for diabetic kidney disease with a perspective on inflammation in the kidneys. Such insights may enable a targeted approach to discovering novel drugs against chronic kidney disease in type 2 diabetes.</span></p></div>","PeriodicalId":21756,"journal":{"name":"Seminars in nephrology","volume":null,"pages":null},"PeriodicalIF":2.8000,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Seminars in nephrology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0270929523001419","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Progression of chronic kidney disease in type 2 diabetes has been understood conventionally as a consequence of intraglomerular hemodynamic changes and aberrant metabolic pathways. However, an increasing body of experimental evidence has highlighted the role of inflammatory response in the progression of diabetic kidney disease. Macrophage polarization in response to specific microenvironmental stimuli affects the pathology of diabetic kidneys. The diabetic milieu also up-regulates inflammatory cytokines, chemokines, and adhesion molecules, and promotes inflammatory signal transduction pathways, including inflammasomes. Therefore, from a reverse translational perspective, modulation of the inflammatory response may be the driving force of the renoprotective effects of renin-angiotensin system inhibitors, sodium-glucose cotransporter-2 inhibitors, and mineralocorticoid receptor antagonists, all of which have been shown to slow disease progression. Currently, many agents that target the inflammation in the kidneys directly are evaluated in clinical trials. This article discusses recent clinical and experimental milestones in drug development for diabetic kidney disease with a perspective on inflammation in the kidneys. Such insights may enable a targeted approach to discovering novel drugs against chronic kidney disease in type 2 diabetes.
期刊介绍：
Seminars in Nephrology is a timely source for the publication of new concepts and research findings relevant to the clinical practice of nephrology. Each issue is an organized compendium of practical information that serves as a lasting reference for nephrologists, internists and physicians in training.
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