Steno Diabetes Center Copenhagen, Gentofte Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Curr Opin Nephrol Hypertens. 2020 Jan;29(1):145-151. doi: 10.1097/MNH.0000000000000557.
Diabetic kidney disease is a growing problem leading to end-stage kidney disease but also atherosclerotic cardiovascular disease and heart failure. Aldosterone is a key risk factor promoting inflammation and fibrosis causing cardio-renal failure. Current options and challenges with mitigating the risk of aldosterone are reviewed.
More aggressive renin-angiotensin-aldosterone system (RAAS) blockade can be maintained in individuals with hyperkalemia if new potassium binders are added. Aldosterone synthase inhibitors may lower aldosterone without causing hyperkalemia. Novel nonsteroidal mineralocorticoid receptor antagonists (MRA) are able to lower proteinuria and markers of heart failure, with limited potassium problems and without renal impairment. Ongoing clinical trials are evaluating the safety and potential benefits of nonsteroidal MRAs on progression of renal disease and development of cardiovascular outcomes in type 2 diabetes and kidney disease.
Aldosterone is an important driver of inflammation and fibrosis leading to renal and cardiovascular complications. MRA lower albuminuria but data showing prevention of end-stage kidney disease are lacking. Side effects including hyperkalemia have previously prevented long-term studies in diabetic kidney disease but new treatment strategies with potassium binders, aldosterone synthase inhibitors and nonsteroidal MRA have been developed for clinical testing.
糖尿病肾病是导致终末期肾病、动脉粥样硬化心血管疾病和心力衰竭的日益严重的问题。醛固酮是促进炎症和纤维化导致心肾衰竭的关键风险因素。本文综述了减轻醛固酮风险的现有治疗选择和挑战。
如果添加新型钾结合剂,则可在高钾血症患者中维持更积极的肾素-血管紧张素-醛固酮系统(RAAS)阻断治疗。醛固酮合酶抑制剂可降低醛固酮而不引起高钾血症。新型非甾体类盐皮质激素受体拮抗剂(MRA)可降低蛋白尿和心力衰竭标志物,其钾问题和肾功能损害有限。正在进行的临床试验正在评估非甾体 MRA 对 2 型糖尿病和肾脏疾病患者的肾脏疾病进展和心血管结局的安全性和潜在益处。
醛固酮是导致肾脏和心血管并发症的炎症和纤维化的重要驱动因素。MRA 可降低白蛋白尿,但缺乏预防终末期肾病的数据。以前,高钾血症等副作用阻止了糖尿病肾病的长期研究,但已开发出新型治疗策略,包括钾结合剂、醛固酮合酶抑制剂和非甾体 MRA,用于临床测试。