Dhaybi Omar Al, Bakris George
aDepartment of Medicine, Section of Nephrology bSection of Endocrinology, Diabetes and Metabolism, ASH Comprehensive Hypertension Center, University of Chicago Medicine, Chicago, Illinois, USA.
Curr Opin Nephrol Hypertens. 2017 Jan;26(1):50-55. doi: 10.1097/MNH.0000000000000290.
Current evidence showcases the pathologic effects of excess aldosterone in promoting glomerular and tubulointerstitial inflammation and fibrosis through various pathways. The place for mineralocorticoid receptor antagonists (MRAs) in chronic kidney disease (CKD) progression is unclear.
MRAs further reduce albuminuria and blood pressure in CKD patients when used in conjunction with angiotensin-converting enzyme inhibitor or angiotensin receptor blockers. The usage of MRAs as disease-modifying therapy in CKD patients has been hampered by concern over worsening kidney function and hyperkalemia. Recent data from small studies highlight a way that these agents may be used with no fear of hyperkalemia. Additionally, they have been shown to further lower blood pressure and albuminuria when hyperkalemia is no longer a safety issue. Additionally, novel MRAs are in phase 3 clinical trials and these are discussed.
MRAs have a clear role in further reducing very high albuminuria when used with other renin-angiotensin system blockers; however, hyperkalemia is a limiting factor for the use of MRAs. Use of the new potassium binder patiromer has facilitated the use of MRAs in CKD, and novel nonsteroidal MRAs are currently being tested in advanced CKD outcome trials.
目前的证据表明,过量醛固酮通过多种途径促进肾小球和肾小管间质炎症及纤维化的病理作用。盐皮质激素受体拮抗剂(MRAs)在慢性肾脏病(CKD)进展中的地位尚不清楚。
MRAs与血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂联合使用时,可进一步降低CKD患者的蛋白尿和血压。由于担心肾功能恶化和高钾血症,MRAs作为CKD患者疾病改善治疗的应用受到阻碍。小型研究的最新数据突出了一种可无惧高钾血症使用这些药物的方法。此外,当高钾血症不再是安全问题时,它们已被证明可进一步降低血压和蛋白尿。此外,新型MRAs正处于3期临床试验阶段,对此也进行了讨论。
MRAs与其他肾素-血管紧张素系统阻滞剂联合使用时,在进一步降低极高蛋白尿方面具有明确作用;然而,高钾血症是使用MRAs的限制因素。新型钾结合剂帕替罗姆的使用促进了MRAs在CKD中的应用,新型非甾体MRAs目前正在晚期CKD结局试验中进行测试。