Mineralocorticoid Receptor Antagonism in Chronic Kidney Disease.
Mineralocorticoid Receptor Antagonism in Chronic Kidney Disease.
复制标题
DOI：
10.1016/j.ekir.2021.05.027
复制
发表时间：
2021-09
影响因子：
6
通讯作者：
Agarwal R
中科院分区：
文献类型：
--
作者：
Georgianos PI;Agarwal R
在慢性肾脏疾病（CKD）动物模型中，盐皮质激素受体（MR）过度活化会增加钠潴留和高血压，并引起肾脏、血管和心脏的炎症和纤维化;这些过程在心肾疾病的进展中起重要作用。因此，阻断二尖瓣返流是一种有吸引力的治疗干预措施，可延缓CKD的进展并改善心血管发病率和死亡率。非那利酮是一种新型非甾体类MR拮抗剂（MRA），具有独特的作用方式，与目前可用的甾体类MRA不同。在CKD动物模型中，与螺内酯和依普利酮等甾体类MRA相比，非那利酮具有更有利的获益/风险比。在患有2型糖尿病和心脏和/或肾脏疾病的患者中，II期试验显示，与螺内酯、依普利酮或安慰剂相比，非那利酮显示出的益处超过了MR拮抗作用的风险。在CKD和2型糖尿病患者中，一项大型III期试验表明，与安慰剂相比，非那酮改善了肾衰竭和心血管结局。在本文的第一部分，我们探讨了螺内酯和依普利酮在早期和晚期CKD的安全性和有效性。在第二部分中，我们描述了非那利酮的作用机制，并讨论了这种非甾体类MRA作为一种新的治疗机会，以改善CKD患者的临床结局的有前途的作用。
The overactivation of the mineralocorticoid receptor (MR) in animal models of chronic kidney disease (CKD) increases sodium retention and hypertension and provokes inflammation and fibrosis in the kidneys, blood vessels, and the heart; these processes play an important role in the progression of cardiorenal disease. Accordingly, blockade of the MR is an attractive therapeutic intervention to retard the progression of CKD and improve cardiovascular morbidity and mortality. Finerenone is a novel, nonsteroidal MR antagonist (MRA) with a unique mode of action that is distinct from currently available steroidal MRAs. In animal models of CKD, finerenone has a more favorable benefit/risk ratio as compared with the steroidal MRAs such as spironolactone and eplerenone. In patients with type 2 diabetes and heart and/or kidney disease, phase II trials have revealed that compared with spironolactone, eplerenone, or placebo, finerenone displays benefits that exceed the risks of MR antagonism. In patients with CKD and type 2 diabetes, a large phase III trial has shown that, compared with placebo, finerenone improved kidney failure and cardiovascular outcomes. In the first part of this article, we explore the safety and efficacy of spironolactone and eplerenone in early- and late-stage CKD. In the second part, we describe the mechanism of action of finerenone and discuss the promising role of this nonsteroidal MRA as a novel therapeutic opportunity to improve clinical outcomes in patients with CKD.
登录
查看更多内容
DOI：
10.1161/hyp.0000000000000084
发表时间：
2018-11
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Carey RM;Calhoun DA;Bakris GL;Brook RD;Daugherty SL;Dennison-Himmelfarb CR;Egan BM;Flack JM;Gidding SS;Judd E;Lackland DT;Laffer CL;Newton-Cheh C;Smith SM;Taler SJ;Textor SC;Turan TN;White WB;American Heart Association Professional/Public Education and Publications Committee of the Council on Hypertension; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; Council on Genomic and Precision Medicine; Council on Peripheral Vascular Disease; Council on Quality of Care and Outcomes Research; and Stroke Council
通讯作者：
American Heart Association Professional/Public Education and Publications Committee of the Council on Hypertension; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; Council on Genomic and Precision Medicine; Council on Peripheral Vascular Disease; Council on Quality of Care and Outcomes Research; and Stroke Council
影响因子：
3
作者：
Kolkhof, Peter;Delbeck, Martina;Schaefer, Stefan
通讯作者：
Schaefer, Stefan
影响因子：
19.6
作者：
Charytan, David M.;Himmelfarb, Jonathan;Kusek, John
通讯作者：
Kusek, John
影响因子：
3.9
作者：
Gerisch, Michael;Heinig, Roland;Schwarz, Thomas
通讯作者：
Schwarz, Thomas
DOI：
10.1007/s13318-019-00547-x
发表时间：
2019-10-01
影响因子：
1.9
作者：
Heinig, Roland;Lambelet, Marc;Halabi, Atef
通讯作者：
Halabi, Atef