Dojki Farheen K, Bakris George
ASH Comprehensive Hypertension Center, Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Chicago Medicine, Chicago, Illinois, USA.
Curr Opin Nephrol Hypertens. 2017 Sep;26(5):368-374. doi: 10.1097/MNH.0000000000000340.
Current data highlight the pathological aspects of excess aldosterone in promoting glomerular hypertrophy, glomerulosclerosis, and proteinuria in diabetic kidney disease (DKD). The role of nonsteroidal mineralocorticoid receptor antagonists (MRAs) in DKD is being evaluated in ongoing clinical trials.
Recent studies demonstrate beneficial effects of adding MRAs to the treatment regimen of patients with type 2 diabetes with nephropathy. The MRAs spironolactone and eplerenone can protect against organ damage caused by elevated levels of serum aldosterone in patients with heart failure and DKD but are limited by their side effects, for example, hyperkalemia. Finerenone is more selective for the mineralocorticoid receptor than spironolactone and has greater affinity for the mineralocorticoid receptor than eplerenone. It reduces the concentration of aldosterone without causing significant elevation in serum potassium.
MRAs have a clear role in reducing albuminuria when used with other renin-angiotensin system blockers in DKD; however, hyperkalemia limits their use. This article provides an overview of clinical studies with a novel MRA, finerenone, and several nonsteroidal MRAs being studied for treatment in DKD.
当前数据突出了醛固酮过多在促进糖尿病肾病(DKD)中的肾小球肥大、肾小球硬化和蛋白尿方面的病理情况。非甾体类盐皮质激素受体拮抗剂(MRAs)在DKD中的作用正在正在进行的临床试验中进行评估。
最近的研究表明,在2型糖尿病肾病患者的治疗方案中添加MRAs具有有益效果。MRAs螺内酯和依普利酮可以预防心力衰竭和DKD患者因血清醛固酮水平升高而导致的器官损伤,但受到诸如高钾血症等副作用的限制。非奈利酮比螺内酯对盐皮质激素受体更具选择性,并且比依普利酮对盐皮质激素受体具有更高的亲和力。它可降低醛固酮浓度而不会导致血清钾显著升高。
在DKD中,与其他肾素-血管紧张素系统阻滞剂联合使用时,MRAs在减少蛋白尿方面具有明确作用;然而,高钾血症限制了它们的使用。本文概述了使用新型MRA非奈利酮以及几种正在研究用于DKD治疗的非甾体类MRAs的临床研究。