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非奈利酮:一种用于治疗心力衰竭、糖尿病和慢性肾脏病的突破性盐皮质激素受体拮抗剂。

Finerenone: a breakthrough mineralocorticoid receptor antagonist for heart failure, diabetes and chronic kidney disease.

作者信息

Pradhan Akshyaya, Tripathi Umesh Chandra

机构信息

Department of Cardiology, King George's Medical University, Lucknow, Uttar Pradesh, 226003, India.

Department of Cardiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India.

出版信息

Egypt Heart J. 2024 Dec 16;76(1):159. doi: 10.1186/s43044-024-00586-z.

Abstract

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.

摘要

背景

醛固酮被归类为一种在肾上腺皮质球状带产生的盐皮质激素。醛固酮在钠水潴留以及心脏重塑方面具有显著作用,会促进纤维化,随着时间的推移,盐皮质激素受体拮抗剂已抵消了这些有害影响。螺内酯是一种广泛使用的非选择性甾体盐皮质激素受体拮抗剂,效力很强,但有诸如男性乳房发育和高钾血症等严重不良反应。依普利酮是另一种第二代盐皮质激素受体拮抗剂,虽为非甾体且具有选择性,但会导致高钾血症并对肾功能产生不利影响。

主体内容

最近,非奈利酮——一种新型盐皮质激素受体拮抗剂已被引入,它与螺内酯效力相当,但不良反应较少,且能改善心血管结局,尤其是在糖尿病慢性肾衰竭患者中。本文回顾了非奈利酮的物理和化学性质,并将其与已在使用的盐皮质激素受体拮抗剂进行比较,然后介绍了非奈利酮针对特定患者的用途及其未来发展方向。非奈利酮是一种非甾体选择性盐皮质激素受体拮抗剂,在改善糖尿病慢性肾脏病患者肾功能恶化、减少蛋白尿且高钾血症较少方面取得了有前景的结果,同时通过减少心力衰竭事件改善了心血管结局。

结论

盐皮质激素受体拮抗剂在预防肾素 - 血管紧张素 - 醛固酮系统(RAAS)通路对心脏、肾脏和血管的不利影响方面已被证实具有作用。非选择性甾体盐皮质激素受体拮抗剂作用强大,但因其非选择性会产生如男性乳房发育、多毛症以及高钾血症等不良反应。非奈利酮是新型非甾体且高度选择性的盐皮质激素受体拮抗剂,在阻止糖尿病慢性肾脏病患者肾功能恶化、减少蛋白尿、通过减少心力衰竭事件改善心血管结局方面取得了有前景的结果,尽管高钾血症较少。针对特定心力衰竭患者的更多随机研究正在使用非奈利酮进行,以证明尽管有指南指导的药物治疗(GDMT),但在这个有巨大未满足需求的领域它是有价值的。尽管有基线药物治疗,非奈利酮仍可减轻糖尿病和慢性肾脏病患者发生不良肾脏和心脏结局的风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/971a/11649598/6e8f68b830c6/43044_2024_586_Fig1_HTML.jpg

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