对未来的考虑:盐皮质激素受体拮抗剂的当前和未来治疗模式——未满足的需求和服务不足的患者群体

IF 19.3 2区 医学 Q1 UROLOGY & NEPHROLOGY
Murray Epstein
{"title":"对未来的考虑:盐皮质激素受体拮抗剂的当前和未来治疗模式——未满足的需求和服务不足的患者群体","authors":"Murray Epstein","doi":"10.1016/j.kisu.2021.11.008","DOIUrl":null,"url":null,"abstract":"<div><p>The recent successful demonstrations that the nonsteroidal mineralocorticoid receptor (MR) antagonist finerenone provides effective kidney and cardiovascular (CV) protection in patients with chronic kidney disease (CKD) and type 2 diabetes constitutes a platform for considering and implementing an array of future clinical trials in patients with nondiabetic CKD. Activation of the MR, with consequent inflammation and fibrosis, should be operative as a pathogenetic mediator not only in patients with diabetic CKD but also in those with nondiabetic kidney disease. Consequently, it is proposed that MR antagonism therapy will be equally efficacious in patients with nondiabetic CKD. Recently, a major new clinical trial has been initiated testing finerenone in patients with nondiabetic kidney disease (FIND-CKD; NCT05047263). A second clinical development program, FIONA, is dedicated to studies of finerenone in children with glomerular and nonglomerular CKD. Finally, the interrelationship of fibroblast growth factor 23 (FGF23), membrane αKlotho (hereafter called Klotho), and aldosterone may be a propitious subject for future investigation. The interplay and intersection of these seemingly disparate yet intricate relationships may unmask novel, and indeed compelling, opportunities for therapeutic interventions that are capable of interrupting the vicious cycle of excess aldosterone/MR activation and FGF23 secretion with concomitant Klotho insufficiency characteristically present in patients with CKD.</p></div>","PeriodicalId":48895,"journal":{"name":"Kidney International Supplements","volume":null,"pages":null},"PeriodicalIF":19.3000,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2157171621000733/pdfft?md5=ac07a929ec6ce0ee8dd18eac0dd8541c&pid=1-s2.0-S2157171621000733-main.pdf","citationCount":"7","resultStr":"{\"title\":\"Considerations for the future: current and future treatment paradigms with mineralocorticoid receptor antagonists—unmet needs and underserved patient cohorts\",\"authors\":\"Murray Epstein\",\"doi\":\"10.1016/j.kisu.2021.11.008\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>The recent successful demonstrations that the nonsteroidal mineralocorticoid receptor (MR) antagonist finerenone provides effective kidney and cardiovascular (CV) protection in patients with chronic kidney disease (CKD) and type 2 diabetes constitutes a platform for considering and implementing an array of future clinical trials in patients with nondiabetic CKD. Activation of the MR, with consequent inflammation and fibrosis, should be operative as a pathogenetic mediator not only in patients with diabetic CKD but also in those with nondiabetic kidney disease. Consequently, it is proposed that MR antagonism therapy will be equally efficacious in patients with nondiabetic CKD. Recently, a major new clinical trial has been initiated testing finerenone in patients with nondiabetic kidney disease (FIND-CKD; NCT05047263). A second clinical development program, FIONA, is dedicated to studies of finerenone in children with glomerular and nonglomerular CKD. Finally, the interrelationship of fibroblast growth factor 23 (FGF23), membrane αKlotho (hereafter called Klotho), and aldosterone may be a propitious subject for future investigation. The interplay and intersection of these seemingly disparate yet intricate relationships may unmask novel, and indeed compelling, opportunities for therapeutic interventions that are capable of interrupting the vicious cycle of excess aldosterone/MR activation and FGF23 secretion with concomitant Klotho insufficiency characteristically present in patients with CKD.</p></div>\",\"PeriodicalId\":48895,\"journal\":{\"name\":\"Kidney International Supplements\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":19.3000,\"publicationDate\":\"2022-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2157171621000733/pdfft?md5=ac07a929ec6ce0ee8dd18eac0dd8541c&pid=1-s2.0-S2157171621000733-main.pdf\",\"citationCount\":\"7\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Kidney International Supplements\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2157171621000733\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"UROLOGY & NEPHROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Kidney International Supplements","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2157171621000733","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
引用次数: 7

摘要

最近的成功证明,非甾体盐皮质激素受体(MR)拮抗剂finereone为慢性肾脏病(CKD)和2型糖尿病患者提供了有效的肾脏和心血管(CV)保护,这为考虑和实施一系列非糖尿病CKD患者的未来临床试验提供了平台。MR的激活,以及随之而来的炎症和纤维化,不仅在糖尿病CKD患者中,而且在非糖尿病肾病患者中,都应该作为一种致病介质发挥作用。因此,有人提出MR拮抗治疗对非糖尿病CKD患者同样有效。最近,一项新的重大临床试验已经启动,在非糖尿病肾病患者中测试芬瑞酮(FIND-CKD;NCT05047263)。第二个临床开发项目,FIONA,致力于对肾小球和非肾小球CKD儿童进行非雷诺酮的研究。最后,成纤维细胞生长因子23(FGF23)、膜αKlotho(以下称为Klotho)和醛固酮的相互关系可能是未来研究的有利主题。这些看似不同但复杂的关系的相互作用和交叉可能揭示了新的、确实令人信服的治疗干预机会,这些干预能够中断醛固酮/MR过度激活和FGF23分泌的恶性循环,并伴有CKD患者特有的Klotho功能不全。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Considerations for the future: current and future treatment paradigms with mineralocorticoid receptor antagonists—unmet needs and underserved patient cohorts

Considerations for the future: current and future treatment paradigms with mineralocorticoid receptor antagonists—unmet needs and underserved patient cohorts

The recent successful demonstrations that the nonsteroidal mineralocorticoid receptor (MR) antagonist finerenone provides effective kidney and cardiovascular (CV) protection in patients with chronic kidney disease (CKD) and type 2 diabetes constitutes a platform for considering and implementing an array of future clinical trials in patients with nondiabetic CKD. Activation of the MR, with consequent inflammation and fibrosis, should be operative as a pathogenetic mediator not only in patients with diabetic CKD but also in those with nondiabetic kidney disease. Consequently, it is proposed that MR antagonism therapy will be equally efficacious in patients with nondiabetic CKD. Recently, a major new clinical trial has been initiated testing finerenone in patients with nondiabetic kidney disease (FIND-CKD; NCT05047263). A second clinical development program, FIONA, is dedicated to studies of finerenone in children with glomerular and nonglomerular CKD. Finally, the interrelationship of fibroblast growth factor 23 (FGF23), membrane αKlotho (hereafter called Klotho), and aldosterone may be a propitious subject for future investigation. The interplay and intersection of these seemingly disparate yet intricate relationships may unmask novel, and indeed compelling, opportunities for therapeutic interventions that are capable of interrupting the vicious cycle of excess aldosterone/MR activation and FGF23 secretion with concomitant Klotho insufficiency characteristically present in patients with CKD.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
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.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信