临床前景——盐皮质激素受体拮抗剂在慢性肾脏病和2型糖尿病患者中的发展证据

IF 19.3 2区 医学 Q1 UROLOGY & NEPHROLOGY Kidney International Supplements Pub Date : 2022-04-01 DOI:10.1016/j.kisu.2021.11.005
Peter Rossing
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引用次数: 11

摘要

2型糖尿病中的慢性肾脏疾病(CKD)是一个巨大且日益严重的问题,会导致终末期肾病、动脉粥样硬化性心血管疾病和心力衰竭(HF)。醛固酮是促进炎症和纤维化的关键风险因素,而炎症和纤维化会导致心肾功能衰竭。血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂的治疗不能防止盐皮质激素受体的过度激活。本文综述了醛固酮阻断MR过度激活的治疗选择和挑战。尽管在糖尿病和非糖尿病CKD的短期研究中,经典的甾体盐皮质激素受体拮抗剂(MRAs)可以减少蛋白尿,但由于副作用(主要是高钾血症),没有在CKD中进行评估肾功能丧失等硬终点的长期研究。与甾体MRA相比,新型非甾体MRAs可降低蛋白尿和HF标志物,高钾血症风险较低,且无肾损伤。此外,最近的临床试验已经证明,新型、选择性、非甾体MRA精细雷诺酮对CKD和2型糖尿病患者延缓肾脏和心血管疾病(包括HF)进展的疗效。同时,finerenone的安全性良好,很少有患者因高钾血症而停止治疗,即使在肾小球滤过率估计较低(>25ml/min/1.73m2)的研究参与者中也是如此。在CKD和2型糖尿病患者的治疗模式中,新的非甾体MRA(如finerenone)有可能成为一个有吸引力的补充,旨在满足因MR过度激活而导致的炎症和纤维化增加的未满足需求。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Clinical perspective—evolving evidence of mineralocorticoid receptor antagonists in patients with chronic kidney disease and type 2 diabetes

Chronic kidney disease (CKD) in type 2 diabetes is a large and growing problem leading to end-stage kidney disease, atherosclerotic cardiovascular disease, and heart failure (HF). Aldosterone is a key risk factor in promoting inflammation and fibrosis, which causes cardiorenal failure. Treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers does not prevent overactivation of the mineralocorticoid receptor. Therapeutic options and challenges with blocking MR overactivation by aldosterone are reviewed herein. Whereas classic steroidal mineralocorticoid receptor antagonists (MRAs) reduced albuminuria in short-term studies of diabetic and nondiabetic CKD, long-term studies evaluating hard endpoints such as loss of kidney function were not conducted in CKD because of side effects (primarily hyperkalemia). Novel nonsteroidal MRAs reduce proteinuria and markers of HF, with lower risk of hyperkalemia and without renal impairment, in comparison to steroidal MRAs. Furthermore, recent clinical trials have demonstrated the efficacy of the novel, selective, nonsteroidal MRA finerenone to delay progression of kidney and cardiovascular disease, including HF, in patients with CKD and type 2 diabetes. Concomitantly, the safety profile of finerenone is good, with few patients discontinuing treatment because of hyperkalemia, even among study participants with a low estimated glomerular filtration rate (>25 ml/min per 1.73 m2). Novel nonsteroidal MRAs such as finerenone hold the potential to be an attractive addition to the treatment paradigm in the management of patients with CKD and type 2 diabetes, targeting the unmet need of managing increased inflammation and fibrosis attributable to MR overactivation.

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来源期刊
Kidney International Supplements
Kidney International Supplements UROLOGY & NEPHROLOGY-
CiteScore
11.80
自引率
0.00%
发文量
13
期刊介绍: Kidney International Supplements is published on behalf of the International Society of Nephrology (ISN) and comes complimentary as part of a subscription to Kidney International. Kidney International Supplements is a peer-reviewed journal whose focus is sponsored, topical content of interest to the nephrology community.
期刊最新文献
Editorial Board Table of Contents Variations in kidney care management and access: regional assessments of the 2023 International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA) Update on variability in organization and structures of kidney care across world regions Capacity for the management of kidney failure in the International Society of Nephrology Newly Independent States and Russia region: report from the 2023 ISN Global Kidney Health Atlas (ISN-GKHA)
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