Potential Benefit of Mineralocorticoid Receptor Antagonists in Kidney Diseases
Since the last two decades, a major paradigm shift occurred in our understanding of the physiological and pathophysiological roles of the mineralocorticoid receptor (MR). Expression of the MR in cells/tissues not involved in sodium/potassium balance and extracellular volume homeostasis, i.e., the primary role of the aldosterone/MR complex, paved the way to the discovery of unsuspected implications of MR in a variety of cellular processes and pathological consequences. It also opens the possibility for quick translation to the bedside using available MR antagonists (MRAs) such as spironolactone, canrenone, or eplerenone or using the more recently developed various nonsteroidal MRAs that are not yet marketed. Landmark clinical trials like RALES, EPHESUS, or EMPHASIS well established that MRAs provide great benefits in patients with heart failure and spironolactone or eplerenone have been recommended in these patients. The deep understanding provided by preclinical studies in various domains stimulated the possibility to extend the use of MRAs to new fields, including renal diseases even if MRAs are currently contraindicated or used with great caution in patients with renal function impairment due to the higher risk of hyperkalemia associated with MRA therapy in this at-risk population. The present review presents preclinical data supporting potential indications in renal diseases.