The Ascent of Mineralocorticoid Receptor Antagonists in Diabetic Nephropathy.

IF 3.2 Q2 Pharmacology, Toxicology and Pharmaceutics Current clinical pharmacology Pub Date : 2019-01-01 DOI:10.2174/1574884713666181116100946
Luxitaa Goenka, Raghavan Padmanaban, Melvin George
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引用次数: 13

Abstract

Diabetic nephropathy is defined as a decline in the renal function and an increase in the amount of albuminuria (>300 mg/day). The interruption of the renin-angiotensin-aldosterone system (RAAS) by well-established therapies such as angiotensin-converting enzyme inhibitor, angiotensin receptor blockers, calcium channel blockers or diuretics has been beneficial in reducing the progression of renal diseases; however, there is an increase in the levels of aldosterone due to the aldosterone escape phenomenon. Newer and novel approaches to counteract this aldosterone breakthrough while accentuating the anti-hypertensive and anti-proteinuric effects of these agents would be ideal and mineralocorticoid receptor antagonists fit in this slot perfectly. This review attempted to evaluate the safety and efficacy of and mineralocorticoid receptor antagonists for diabetic nephropathy. Presently mineralocorticoid receptor antagonists such as spironolactone, eplerenone and finerenone are being investigated as both monotherapies and as additional therapies. Clinical studies have shown that these drugs have been effective in the reduction of blood pressure, urinaryalbumin- excretion and estimated glomerular filtration rate. The commonly observed adverse effects are hyperkalemia, gynaecomastia and vaginal bleeding, that are bothersome with spironolactone seems to be avoidable if these patients are switched to non-steroidal and mineralocorticoid receptor antagonists such as finerenone and eplerenone. Most of the studies have only evaluated the shortterm effects of mineralocorticoid receptor antagonists on diabetic nephropathy. Hard outcomes such as cardiovascular events, creatinine doubling, progression to end-stage renal disease, mortality and the need for temporary or permanent dialysis need to be studied with these molecules.

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糖皮质激素受体拮抗剂在糖尿病肾病中的应用。
糖尿病肾病被定义为肾功能下降和蛋白尿量增加(>300 mg/天)。通过血管紧张素转换酶抑制剂、血管紧张素受体阻滞剂、钙通道阻滞剂或利尿剂等成熟疗法中断肾素-血管紧张素-醛固酮系统(RAAS)有利于减少肾脏疾病的进展;然而,由于醛固酮逃逸现象,醛固酮水平升高。新的和新颖的方法来抵消醛固酮的突破,同时强调这些药物的抗高血压和抗蛋白尿作用将是理想的,而矿皮质激素受体拮抗剂正好适合这一位置。本综述试图评价钙皮质激素受体拮抗剂治疗糖尿病肾病的安全性和有效性。目前,矿物皮质激素受体拮抗剂如螺内酯、依普利酮和芬尼酮正在作为单一疗法和附加疗法进行研究。临床研究表明,这些药物在降低血压、尿白蛋白排泄和估计肾小球滤过率方面是有效的。通常观察到的不良反应是高钾血症、妇科乳房发育和阴道出血,如果这些患者改用非甾体和矿物皮质激素受体拮抗剂,如芬尼酮和依普利酮,这些副作用似乎是可以避免的。大多数研究只评估了矿皮质激素受体拮抗剂对糖尿病肾病的短期作用。需要用这些分子研究诸如心血管事件、肌酐加倍、进展到终末期肾病、死亡率和需要暂时或永久透析等硬结局。
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Current clinical pharmacology
Current clinical pharmacology PHARMACOLOGY & PHARMACY-
CiteScore
3.60
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期刊介绍: Current Clinical Pharmacology publishes frontier reviews on all the latest advances in clinical pharmacology. The journal"s aim is to publish the highest quality review articles in the field. Topics covered include: pharmacokinetics; therapeutic trials; adverse drug reactions; drug interactions; drug metabolism; pharmacoepidemiology; and drug development. The journal is essential reading for all researchers in clinical pharmacology.
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