非格列酮:治疗心力衰竭、糖尿病和慢性肾病的突破性矿物皮质激素受体拮抗剂。

Akshyaya Pradhan, Umesh Chandra Tripathi
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引用次数: 0

摘要

背景:醛固酮是肾上腺皮质肾小球区产生的一种矿质皮质激素。醛固酮在钠和水潴留、心脏重塑、促进纤维化等方面具有相当大的作用,这些有害影响已逐渐被矿物皮质激素受体拮抗剂所抵消。螺内酯(Spironolactone)是一种广泛使用的非选择性类固醇 MRA,具有强效作用,但有严重的不良反应,如妇科炎症和高钾血症。另一种第二代 MRA--依普利酮(Eplerenone)虽然是非类固醇和选择性的,但会导致高钾血症并对肾功能产生不良影响:最近推出的新型 MRA 非格列酮(Finerenone-)与螺内酯(spironolactone)的药效相同,但不良反应较少,可改善心血管预后,尤其是对慢性肾衰竭合并糖尿病患者的预后。文章回顾了非奈酮的物理和化学特性,并将其与已在使用的 MRA 进行了比较,然后介绍了非奈酮的患者特定用途及其未来的发展方向。非奈瑞酮是一种非甾体类选择性 MRA,在改善慢性肾功能衰竭合并 DM 患者的肾功能恶化、减少白蛋白尿和高钾血症方面具有良好效果,同时还能通过减少心衰事件改善心血管预后:结论:矿物质皮质激素受体拮抗剂在预防 RAAS 通路对心脏、肾脏和血管的不良影响方面发挥着公认的作用。非选择性类固醇 MRA 具有强效作用,但由于其非选择性,会产生妇科炎症、多毛症和高钾血症等不良反应,而菲尼酮是一种新型的非类固醇和高选择性 MRA,在阻止慢性肾功能衰竭合并糖尿病患者的肾功能恶化、减少白蛋白尿、通过减少心力衰竭事件改善心血管预后(尽管高钾血症较少)方面具有良好效果。目前正在对专门的心力衰竭患者进行更多的非奈酮随机研究,以证明它在这一领域的价值,尽管有 GDMT,但仍有大量需求未得到满足。尽管已接受了基线药物治疗,但非奈酮仍能减轻糖尿病和慢性肾功能衰竭患者的肾脏和心脏不良预后风险。
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Finerenone: a breakthrough mineralocorticoid receptor antagonist for heart failure, diabetes and chronic kidney disease.

Background: Aldosterone is categorized as a mineralocorticoid hormone produced in the zona glomerulosa of the adrenal cortex. Aldosterone has considerable action in sodium and water retention along with cardiac remodeling, promoting fibrosis and these detrimental effects have been counteracted by mineralocorticoid receptors antagonists over time. Spironolactone, a non-selective steroidal MRA used extensively is potent but has serious adverse effects like gynecomastia and hyperkalemia. Eplerenone another second generation MRA, though non-steroidal and selective causes hyperkalemia and adversely effecting renal functions.

Main body: Recently Finerenone- a novel MRA has been introduced which is as potent like spironolactone with less adverse effects and improved cardiovascular outcomes particularly in chronic kidney failure with diabetes. The article reviews the physical and chemical properties of Finerenone and compares it with MRAs already in use, and then about the patient specific uses of Finerenone and future avenues of it. Finerenone is non-steroidal selective MRA, with promising results in improving the deterioration of renal functions in CKD with DM, reducing albuminuria with less hyperkalemia along with improvement in cardiovascular outcomes by reducing heart failure events.

Conclusion: Mineralocorticoid receptor antagonists have a proven role in preventing the adverse effects of RAAS pathway on heart, kidneys and blood vessels. Non-selective steroidal MRAs have potent action but by virtue of their non-selectivity associated with adverse effects like gynecomastia, hirsutism along with hyperkalemia Finerenone is novel non-steroidal & highly selective MRA, with promising results in halting the deterioration of renal functions in CKD with DM, reducing albuminuria, improvement in cardiovascular outcomes by reducing heart failure events albeit with less hyperkalemia. More randomized studies in dedicated HF patients are ongoing with Finerenone to prove it is worth in this sector with huge unmet need despite GDMT. Finerenone alleviates the risk of adverse renal and cardiac outcomes in patients with diabetes and CKD despite baseline medical therapy.

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