Mineralocorticoid receptors in the pathophysiology of chronic kidney diseases and the metabolic syndrome

Recent studies indicate that aldosterone/mineralocorticoid receptor (MR) is a major contributor of chronic kidney disease (CKD) progression. Aldosterone/MR induces glomerular podocyte injury, causing the disruption of the glomerular filtration barrier and proteinuria. Conversely, MR antagonists substantially reduce proteinuria, which can be partly attributable to the protective effects on podocytes. Aldosterone excess, caused by adipocyte-derived aldosterone-releasing factors and other mechanisms, can be pathologically important in the renal complication of metabolic syndrome. A rat model of metabolic syndrome exhibits podocyte injury and proteinuria with serum aldosterone elevation, and the renal damage is prevented by MR blockade. Accumulating data also indicate that MR inhibition can confer renoprotection in a subgroup with low or normal aldosterone levels. We have recently identified the cross-talk between MR and small GTPase Rac1, providing one theoretical basis for the renoprotective effects of MR antagonists in non-high-aldosterone subjects. MR blockade can be a promising strategy for preventing CKD progression, and future clinical trials will conclusively determine the efficacy and tolerability of selective MR inhibition in CKD and metabolic syndrome.

► Aldosterone/mineralocorticoid receptor (MR) is a major contributor of kidney disease progression.
► Aldosterone excess also causes renal complication in metabolic syndrome.
► MR activity can be regulated locally, including through the interaction with Rac1 GTPase.
► MR blockade can be a promising strategy for preventing kidney disease progression.