Goenka Luxitaa, Padmanaban Raghavan, George Melvin
Department of Clinical Pharmacology, SRM Medical College Hospital and Research Centre, Kattankulathur, Chennai, Tamil Nadu, 603203, India.
Department of Nephrology, SRM Medical College Hospital and Research Centre, Kattankulathur, Chennai, Tamil Nadu, 603203, India.
Curr Clin Pharmacol. 2019;14(2):78-83. doi: 10.2174/1574884713666181116100946.
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.
糖尿病肾病的定义为肾功能下降以及蛋白尿增加(>300毫克/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阻断肾素-血管紧张素-醛固酮系统(RAAS),已有助于减少肾脏疾病的进展;然而,由于醛固酮逃逸现象,醛固酮水平会升高。在增强这些药物的抗高血压和抗蛋白尿作用的同时,对抗这种醛固酮突破的更新颖方法将是理想的,而盐皮质激素受体拮抗剂完全符合这一要求。本综述试图评估盐皮质激素受体拮抗剂对糖尿病肾病的安全性和疗效。目前,螺内酯、依普利酮和非奈利酮等盐皮质激素受体拮抗剂正在作为单一疗法和辅助疗法进行研究。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有效。常见的不良反应是高钾血症、男性乳房发育和阴道出血,如果将这些患者改用非甾体类盐皮质激素受体拮抗剂如非奈利酮和依普利酮,与螺内酯相关的这些不良影响似乎是可以避免的。大多数研究仅评估了盐皮质激素受体拮抗剂对糖尿病肾病的短期影响。需要用这些药物研究心血管事件、肌酐翻倍、进展为终末期肾病、死亡率以及临时或永久透析需求等硬性结局。