Purpose of Review

Novel non-steroidal mineralocorticoid receptor (MR) antagonists (MRAs) are a new class of drugs blocking adverse MR-mediated effects with an improved benefit-risk profile compared to steroidal MRAs. This review will provide information on the preclinical and clinical pharmacology of this new drug class and will discuss their future clinical applications in patients with cardiorenal disease.

Recent Findings

Non-steroidal MRAs such as esaxerenone, AZD9977, apararenone, ocedurenone (KBP-5074), and finerenone are newly approved or in clinical development for patients with cardiorenal disease including type 2 diabetes (T2D) and chronic kidney disease (CKD), hypertension −/+ CKD or heart failure. Unlike steroidal MRAs, non-steroidal MRAs do not induce sex hormone-related side effects and appear to mediate a lower risk of hyperkalemia while maintaining compelling clinical efficacy. Recently, new data from several clinical trials with non-steroidal MRAs have been published (e.g., FIDELIO-DKD, FIGARO-DKD, ESAX-DN, and BLOCK-CKD), and additional studies are currently underway (e.g., FINEARTS-HF and CLARION-CKD). These data and the clinical scientific basis for the ongoing studies will be discussed.

Summary

Non-steroidal MRAs have been extensively explored in diabetic kidney disease. Selected candidates of this drug class reduced UACR in patients with varying degrees of CKD and T2D and have shown convincing cardiorenal protection, in particular finerenone. Furthermore, finerenone is currently tested in patients with heart failure with preserved ejection fraction.

中文翻译：

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新型非甾体盐皮质激素拮抗剂对糖尿病患者的心血管和肾脏益处

审查目的

新型非类固醇盐皮质激素受体 (MR) 拮抗剂 (MRA) 是一类新型药物，可阻断 MR 介导的不良反应，与类固醇 MRA 相比，其获益风险状况有所改善。本综述将提供该新药类别的临床前和临床药理学信息，并将讨论其未来在心肾疾病患者中的临床应用。

最近的发现

非甾体 MRA，如 esaxerenone、AZD9977、apararenone、ocedurenone (KBP-5074) 和 Finerenone 是新批准或处于临床开发阶段的，用于治疗心肾疾病患者，包括 2 型糖尿病 (T2D) 和慢性肾病 (CKD)、高血压 - /+ CKD 或心力衰竭。与类固醇 MRA 不同，非类固醇 MRA 不会引起性激素相关副作用，并且似乎可以降低高钾血症风险，同时保持引人注目的临床疗效。最近，多项非甾体 MRA 临床试验的新数据已发表（例如 FIDELIO-DKD、FIGARO-DKD、ESAX-DN 和 BLOCK-CKD），目前正在进行更多研究（例如 FINEARTS-HF 和号角-CKD）。将讨论这些数据和正在进行的研究的临床科学基础。

概括

非类固醇 MRA 已在糖尿病肾病中得到广泛探索。该药物类别的选定候选药物可降低不同程度 CKD 和 T2D 患者的 UACR，并显示出令人信服的心肾保护作用，尤其是 Finerenone。此外，finerenone 目前正在射血分数保留的心力衰竭患者中进行测试。