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非奈利酮作为糖尿病肾病新型治疗选择的意义:一项范围综述,重点关注非奈利酮3期试验的心肾结局

The significance of finerenone as a novel therapeutic option in diabetic kidney disease: a scoping review with emphasis on cardiorenal outcomes of the finerenone phase 3 trials.

作者信息

Arici Mustafa, Altun Bulent, Araz Mustafa, Atmaca Aysegul, Demir Tevfik, Ecder Tevfik, Guz Galip, Gogas Yavuz Dilek, Yildiz Alaattin, Yilmaz Temel

机构信息

Department of Nephrology, Hacettepe University Faculty of Medicine, Ankara, Türkiye.

Department of Endocrinology and Metabolic Diseases, Gaziantep University Faculty of Medicine, Gaziantep, Türkiye.

出版信息

Front Med (Lausanne). 2024 Jun 14;11:1384454. doi: 10.3389/fmed.2024.1384454. eCollection 2024.

Abstract

This scoping review prepared by endocrinology and nephrology experts aimed to address the significance of finerenone, as a novel therapeutic option, in diabetic kidney disease (DKD), based on the biological prospect of cardiorenal benefit due to non-steroidal mineralocorticoid receptor antagonist (MRA) properties, and the recent evidence from the finerenone phase 3 program clinical trials. The importance of finerenone in slowing DKD progression was critically reviewed in relation to the role of MR overactivation in the pathogenesis of cardiorenal disease and unmet needs in the current practice patterns. The efficacy and safety outcomes of finerenone phase III study program including FIDELIO-DKD, FIGARO-DKD and FIDELITY were presented. Specifically, perspectives on inclusion of patients with preserved estimated glomerular filtration rate (eGFR) or high albuminuria, concomitant use of sodium-glucose co-transporter-2 inhibitor (SGLT2i) or glucagon-like peptide 1 receptor agonist (GLP-1 RA), baseline glycated hemoglobin (HbA1c) level and insulin treatment, clinically meaningful heart failure outcomes and treatment-induced hyperkalemia were addressed. Finerenone has emerged as a new therapeutic agent that slows DKD progression, reduces albuminuria and risk of cardiovascular complications, regardless of the baseline HbA1c levels and concomitant treatments (SGLT2i, GLP-1 RA, or insulin) and with a favorable benefit-risk profile. The evolving data on the benefit of SGLT2is and non-steroidal MRAs in slowing or reducing cardiorenal risk seem to provide the opportunity to use these pillars of therapy in the management of DKD, after a long-period of treatment scarcity in this field. Along with recognition of the albuminuria as a powerful marker to detect those patients at high risk of cardiorenal disease, these important developments would likely to impact standard-of-care options in the setting of DKD.

摘要

由内分泌学和肾脏病学专家撰写的这项范围综述,旨在基于非甾体类盐皮质激素受体拮抗剂(MRA)特性对心肾有益的生物学前景以及非奈利酮3期项目临床试验的最新证据,探讨非奈利酮作为一种新型治疗选择在糖尿病肾病(DKD)中的重要性。结合盐皮质激素受体过度激活在心肾疾病发病机制中的作用以及当前实践模式中未满足的需求,对非奈利酮在减缓DKD进展方面的重要性进行了批判性综述。介绍了非奈利酮3期研究项目(包括FIDELIO-DKD、FIGARO-DKD和FIDELITY)的疗效和安全性结果。具体而言,探讨了关于纳入估算肾小球滤过率(eGFR)保留或蛋白尿高的患者、同时使用钠-葡萄糖协同转运蛋白2抑制剂(SGLT2i)或胰高血糖素样肽1受体激动剂(GLP-1 RA)、基线糖化血红蛋白(HbA1c)水平和胰岛素治疗、具有临床意义的心力衰竭结果以及治疗引起的高钾血症等方面的观点。非奈利酮已成为一种新的治疗药物,可减缓DKD进展、降低蛋白尿和心血管并发症风险,无论基线HbA1c水平和同时进行的治疗(SGLT2i、GLP-1 RA或胰岛素)如何,且具有良好的效益风险比。在该领域长期缺乏治疗方法之后,关于SGLT2i和非甾体类MRA在减缓或降低心肾风险方面益处的不断演变的数据,似乎为在DKD管理中使用这些治疗支柱提供了机会。随着蛋白尿被公认为检测心肾疾病高危患者的有力标志物,这些重要进展可能会影响DKD背景下的标准治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4266/11214281/beefacb3193a/fmed-11-1384454-g001.jpg

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