Clinical effect of nonsteroidal mineralocorticoid receptor (MR) antagonists in the treatment of diabetic kidney disease: expectations as a new therapeutic strategy.

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.