Mineralocorticoid receptor antagonists promote renal immunosenescence

Chronic kidney disease (CKD) is often associated with chronic inflammation, influenced by the activation of mineralocorticoid receptors (MR). This review focuses on changes in immune cells and explores the important role that MR antagonists (MRAs), especially the new nonsteroidal MRA, finerenone, play in alleviating renal and cardiac injury by affecting the transformation of stimulated immune cells. We found that MR can promote the transformation of macrophages to M1 pro-inflammatory phenotype through IL-14 receptor and mitogen-activated protein kinase (MAPK)-JNK. MR also activates helper T cells and reduces the generation of regulatory T cells by promoting the interaction between nuclear factor and activator protein-1, increasing the secretion of IL-2 and IL-18, increasing the expression of CD38 and CD69, especially the IL-17/IL-23 axis. The above immune system changes jointly mediate inflammation leading to kidney damage and fibrosis. In addition, we propose that the NLRP3 inflammasome is associated with macrophage imbalance. Preclinical studies indicate that finerenone effectively reduces inflammation and prevents structural kidney damage without significant systemic blood pressure changes. These data will provide some ideas for further research in the field of immune mechanisms in future, and drug research targeting specific targets and channels may also become a new type of diagnostic and treatment measure.