2型糖尿病患者的慢性肾病:药物作用的新靶点

IF 0.7 Q4 ENDOCRINOLOGY & METABOLISM
Diabetes Mellitus Pub Date : 2022-11-30 DOI:10.14341/dm12944
N. P. Trubitsyna, N. V. Zaitseva, A. S. Severinа, M. Shamkhalova
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引用次数: 0

摘要

2型糖尿病(DM2)是一种具有重要社会意义的疾病,由于发病率的上升而成为一种非传染性流行病。慢性肾病(CKD)是糖尿病最常见的并发症之一。40-50%的DM2患者出现肾损伤体征和/或肾小球滤过率(eGFR)下降。三组因素被认为是DM2中CKD发生和进展的基础:代谢、血流动力学、炎症和纤维化。现有用于CKD和DM2患者的药物首先针对血流动力学和代谢紊乱,但它们对炎症和纤维化的作用是间接的。矿化皮质激素受体(MR)的过度激活被认为是DM2患者因炎症和纤维化引起的终末器官损伤的主要触发因素之一。选择性非甾体MR拮抗剂(MRA)作为一类新型药物的开发旨在通过阻断CKD发展的这一病理生理途径来证明其积极作用,并克服甾体MRAs的缺点。因此,CKD患者在DM2中MR的病理生理过度激活并随后的炎症和纤维化被认为是具有心脏肾脏保护作用的新药的有希望的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Chronic kidney disease in patients with type 2 diabetes: new targets of medicine action
Diabetes mellitus type 2 (DM2) is socially important disease, becoming non-infectious epidemic due to increasing prevalence. Chronic kidney disease (CKD) is one of the most common diabetic complications. Kidney injury signs and/or estimated glomerular filtration rate (eGFR) decrease are seen in 40-50% of patients with DM2. Three groups of factors are considered to be the basis of CKD development and progression in DM2: metabolic, hemodynamic, inflammation and fibrosis. Existing drugs that are used in patients with CKD and DM2 first of all target hemodynamic and metabolic disturbances, but their action against inflammation and fibrosis is indirect. Hyperactivation of mineralocorticoid receptors (MR) is considered as one of the main trigger factors of end-organ damage in patients with DM2 due to inflammation and fibrosis. Development of selective nonsteroidal MR antagonists (MRA) as a new class of medications is directed to demonstrate positive effects from blocking this pathophysiological pathway of CKD development and overcome the steroidal MRAs’ shortcomings. Hence pathophysiological hyperactivation of MR with subsequent inflammation and fibrosis in patients with CKD in DM2 is considered a promising therapeutic target for the new drugs with cardionephroprotective effect.
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来源期刊
Diabetes Mellitus
Diabetes Mellitus ENDOCRINOLOGY & METABOLISM-
CiteScore
1.90
自引率
40.00%
发文量
61
审稿时长
7 weeks
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