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非类固醇盐皮质激素受体拮抗剂对慢性肾脏病患者心肾保护研究进展

刘雯瑜, 郁胜强^*

海军军医大学第二附属医院肾脏病科，上海 200003

摘要

盐皮质激素受体拮抗剂不仅可以作为醛固酮拮抗剂和利尿剂应用于原发性高血压等疾病的治疗，还可以通过抑制炎症和纤维化对心肾产生保护作用。自第一代类固醇盐皮质激素受体拮抗剂——螺内酯发现到现在，已经研发出了两种获批应用于临床的非类固醇盐皮质激素受体拮抗剂——非奈利酮和艾莎利酮，其具有高亲和力、高选择性、心肾均衡分布等优点，可作为心肾保护药物应用于临床。本文回顾了盐皮质激素受体拮抗剂的发展史，对盐皮质激素受体导致炎症、纤维化的病理生理学机制和各代盐皮质激素受体拮抗剂的异同进行了阐述，特别对非奈利酮和艾莎利酮的III期临床研究结果进行了归纳分析，并综述了非类固醇盐皮质激素受体拮抗剂对慢性肾脏病患者心肾保护的研究进展。

关键词： 非类固醇盐皮质激素受体拮抗剂; 2型糖尿病; 慢性肾脏病; 心血管疾病

Research progress on the cardiorenal protection of non-steroid mineralocorticoid receptor antagonists in patients with chronic kidney disease

LIU Wen-Yu, YU Sheng-Qiang^*

Department of Nephrology, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China

Abstract

Mineralocorticoid receptor antagonists not only are used as a diuretics to treat essential hypertension, but also protect the heart and kidney by inhibiting inflammation and fibrosis. Since the discovery of spironolactone, the first generation of mineralocorticoid receptor antagonist, two types of non-steroid mineralocorticoid receptor antagonists (finerenone and esaxerenone) approved for clinical use have been developed, which have the advantages of high affinity, high selectivity and balanced distribution in heart and kidney, and can be used in clinic as a cardiorenal protective drug. In this paper, the development history of mineralocorticoid receptor antagonists was reviewed, and the pathophysiological mechanism of inflammation and fibrosis caused by mineralocorticoid receptors and the similarities and differences of different generations of mineralocorticoid receptor antagonists were analyzed. In particular, the phase III clinical research evidence of finerenone and esaxerenone was discussed. This paper also reviews the research progress of cardiorenal protection of non-steroid mineralocorticoid receptor antagonists in patients with chronic kidney disease.

Key words: non-steroid mineralocorticoid receptor antagonists; type 2 diabetes; chronic kidney disease; cardiovascular disease

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通讯作者：郁胜强　　E-mail: ysqdd1@126.com

引用本文：

刘雯瑜, 郁胜强. 非类固醇盐皮质激素受体拮抗剂对慢性肾脏病患者心肾保护研究进展[J]. 生理学报 2022; 74 (6): 1023-1030.

LIU Wen-Yu, YU Sheng-Qiang. Research progress on the cardiorenal protection of non-steroid mineralocorticoid receptor antagonists in patients with chronic kidney disease. Acta Physiol Sin 2022; 74 (6): 1023-1030 (in Chinese with English abstract).