Zhai Shuhui, Ma Baisheng, Chen Weiwei, Zhao Qini
Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun, China.
Front Cardiovasc Med. 2024 Sep 23;11:1476029. doi: 10.3389/fcvm.2024.1476029. eCollection 2024.
Multiple studies have shown that finerenone (BAY 94-8862), a third-generation non-steroidal mineralocorticoid receptor antagonist (MRA), possesses different or superior mechanisms of action to traditional MRAs. Specifically, animal and cell-based experiments have demonstrated that this compound exerts multiple effects including fibrosis inhibition, reduced pulmonary artery pressure, improved diabetic retinopathy, enhanced endothelial functions, metabolic optimization as well as reduced oxidative stress, thereby exerting overall positive effects on renal and cardiovascular diseases. Consequently, clinical research, such as the FIGARO-DKD and FIDELIO-DKD trials, has demonstrated dual benefits for patients with type 2 diabetes mellitus and chronic kidney disease (T2DM-CKD), especially by validating MRAs' potential in reducing risks of renal and cardiovascular composite endpoints. Currently, cardiovascular indications for finerenone are limited to patients with T2DM-CKD, while its use in non-T2DM CKD patients remains at clinical trial stages. Despite showing good safety and efficacy in T2DM-CKD patients, there are insufficient corresponding data for those presenting chronic kidney disease without diabetes (ndCKD). Furthermore, the application of this compound in diseases such as primary aldosteronism and its association with cancer risk need to be further validated through larger-scale and longer-term clinical studies. Nevertheless, the development of finerenone provides an additional option for treating cardiovascular and renal diseases. With further research, it is expected that finerenone will be relevant to a broader range of CKD patient populations by addressing current knowledge gaps to comprehensively evaluate its clinical value and potentially alter existing treatment strategies. The current review aims to comprehensively analyze the basic research and clinical advancements involving finerenone in order to explore its prospects for treating cardiovascular and renal diseases, while addressing unmet needs in current treatment strategies. Additionally, through a comprehensive analysis of relevant research findings, a deeper understanding of finerenone's drug characteristics will be provided alongside scientific guidance for future treatment strategies and their clinical significance.
多项研究表明，非奈利酮（BAY 94-8862）作为第三代非甾体类盐皮质激素受体拮抗剂（MRA），其作用机制与传统MRA不同或更具优势。具体而言，基于动物和细胞的实验已证明，该化合物具有多种作用，包括抑制纤维化、降低肺动脉压力、改善糖尿病视网膜病变、增强内皮功能、优化代谢以及减轻氧化应激，从而对肾脏和心血管疾病产生总体积极影响。因此，FIGARO-DKD和FIDELIO-DKD等临床研究已证明，对于2型糖尿病和慢性肾脏病（T2DM-CKD）患者具有双重益处，特别是通过验证MRA在降低肾脏和心血管复合终点风险方面的潜力。目前，非奈利酮的心血管适应症仅限于T2DM-CKD患者，而其在非T2DM CKD患者中的应用仍处于临床试验阶段。尽管在T2DM-CKD患者中显示出良好的安全性和有效性，但对于无糖尿病的慢性肾脏病（ndCKD）患者，相应数据不足。此外，该化合物在原发性醛固酮增多症等疾病中的应用及其与癌症风险的关联，需要通过更大规模和更长期的临床研究进一步验证。尽管如此，非奈利酮的研发为治疗心血管和肾脏疾病提供了额外选择。随着进一步研究，预计非奈利酮将通过填补当前知识空白，全面评估其临床价值并可能改变现有治疗策略，从而与更广泛的CKD患者群体相关。本综述旨在全面分析涉及非奈利酮的基础研究和临床进展，以探索其治疗心血管和肾脏疾病的前景，同时解决当前治疗策略中未满足的需求。此外，通过对相关研究结果的全面分析，将更深入地了解非奈利酮的药物特性，并为未来治疗策略及其临床意义提供科学指导。
