Department of Internal Medicine, Division of Nephrology and Hypertension, International University of Health and Welfare School of Medicine, Mita Hospital, 1-4-3, Mita, Minato-ku, Tokyo, 108-8329, Japan.
Hypertens Res. 2022 Aug;45(8):1310-1321. doi: 10.1038/s41440-022-00940-1. Epub 2022 Jun 20.
Diabetes mellitus is the main cause of chronic kidney disease (CKD) in Japan and worldwide. Although angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type 1 receptor blockers (ARBs) are basic drugs for the treatment of CKD with diabetes (diabetic kidney disease, DKD) with albuminuria and/or proteinuria, it has also become clear that the use of an ACE inhibitor or ARB alone is not fully sufficient. We have previously reported the clinical effects of mineralocorticoid receptor (MR) antagonists and recommended their use in addition to renin-angiotensin system inhibitors. Recently, new types of nonsteroidal MR antagonists have been developed, and the results of a large-scale study are expected. Nonsteroidal MR antagonists are distributed in the heart, lungs, liver, and kidneys when administered orally and are characterized by their equivalent distribution between the heart (nonepithelial tissue) and kidneys (epithelial tissue). We summarize the latest evidence regarding the use of nonsteroidal MR antagonists in the treatment of DKD. Hyperkalemia and renal dysfunction are frequent during MR antagonist treatment. However, with careful and combined monitoring of these two conditions, the effectiveness of MR antagonists will not be diminished; conversely, it is apparent that patients at such risk will benefit more from the addition of an MR antagonist to the treatment regimen. The most important measure against hyperkalemia is the regular monitoring of serum potassium levels and renal function. The safest and most reliable measure against hyperkalemia is the combined use of a new oral potassium adsorbent that has high potassium selectivity and few side effects. In DKD treatment, it is important to continue using MR antagonists without interruption as much as possible.
糖尿病是日本乃至全球慢性肾脏病（CKD）的主要病因。血管紧张素转换酶（ACE）抑制剂和血管紧张素 II 型 1 型受体阻滞剂（ARB）是治疗伴有白蛋白尿和/或蛋白尿的 CKD（糖尿病肾病，DKD）的基本药物，但也已明确，单独使用 ACE 抑制剂或 ARB 并不完全足够。我们之前报告了盐皮质激素受体（MR）拮抗剂的临床效果，并建议在肾素-血管紧张素系统抑制剂的基础上使用。最近，开发了新型非甾体类 MR 拮抗剂，预计会有大型研究结果公布。非甾体类 MR 拮抗剂口服后分布于心脏、肺、肝和肾脏，其特点是心脏（非上皮组织）和肾脏（上皮组织）之间分布均匀。我们总结了非甾体类 MR 拮抗剂在 DKD 治疗中的最新证据。MR 拮抗剂治疗期间常出现高钾血症和肾功能障碍。然而，通过仔细监测这两种情况并结合监测，MR 拮抗剂的有效性不会降低；相反，显然有此类风险的患者从将 MR 拮抗剂添加到治疗方案中获益更多。预防高钾血症最重要的措施是定期监测血钾和肾功能。预防高钾血症最安全、最可靠的措施是联合使用一种新型口服钾吸附剂，这种吸附剂具有高钾选择性和较少的副作用。在 DKD 治疗中，重要的是尽可能不中断地继续使用 MR 拮抗剂。
