{"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":"12 1","pages":"Pages 69-75"},"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\":\"12 1\",\"pages\":\"Pages 69-75\"},\"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}
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.
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.