Kawanami Daiji, Takashi Yuichi, Muta Yoshimi, Oda Naoki, Nagata Dai, Takahashi Hiroyuki, Tanabe Makito
Department of Endocrinology and Diabetes Mellitus, Fukuoka University School of Medicine, Fukuoka, Japan.
Front Pharmacol. 2021 Oct 28;12:754239. doi: 10.3389/fphar.2021.754239. eCollection 2021.
Diabetic kidney disease (DKD) is a major cause of end-stage kidney disease (ESKD) worldwide. Mineralocorticoid receptor (MR) plays an important role in the development of DKD. A series of preclinical studies revealed that MR is overactivated under diabetic conditions, resulting in promoting inflammatory and fibrotic process in the kidney. Clinical studies demonstrated the usefulness of MR antagonists (MRAs), such as spironolactone and eplerenone, on DKD. However, concerns regarding their selectivity for MR and hyperkalemia have remained for these steroidal MRAs. Recently, nonsteroidal MRAs, including finerenone, have been developed. These agents are highly selective and have potent anti-inflammatory and anti-fibrotic properties with a low risk of hyperkalemia. We herein review the current knowledge and future perspectives of MRAs in DKD treatment.
糖尿病肾病(DKD)是全球终末期肾病(ESKD)的主要病因。盐皮质激素受体(MR)在DKD的发展过程中起重要作用。一系列临床前研究表明,在糖尿病条件下MR过度激活,导致促进肾脏中的炎症和纤维化过程。临床研究证明了MR拮抗剂(MRAs),如螺内酯和依普利酮,对DKD的有效性。然而,对于这些甾体类MRAs,人们对其对MR的选择性和高钾血症的担忧依然存在。最近,包括非奈利酮在内的非甾体类MRAs已被开发出来。这些药物具有高度选择性,具有强大的抗炎和抗纤维化特性,且高钾血症风险低。我们在此综述了MRAs在DKD治疗中的现有知识和未来前景。