Endocrine Abstracts

The mineralocorticoid receptor is a ligand-activated transcription factor involved in renal ion homeostasis and blood pressure control. The MR is also expressed in non-renal targets such as heart, vessels, adipose tissue and immune cells where its role remains to be defined. Pharmacological MR antagonists like spironolactone, canrenoate and eplerenone are used for decades in patients with hypertension or, more recently, with heart failure. Therefore pharmacokinetic and toxicology profiles have been extensively studied. Contra-indications in the nephrology field in particular context like acute renal ischemia or chronic kidney diseases are mainly related to the absence of specific safety trials.

Accumulating data, both at the preclinical (rodent and large animal models) and clinical (safety and interventional studies) levels, will allow repositioning of these drugs and their use in novel clinical indications where, for example, microvascular function and hemodynamics are central.

I will describe the role of aldosterone and mineralocorticoid receptor activation in vascular function and will focus on the microvasculature underlying the physiological and pathophysiological role of vascular MR in retinal and renal injuries where alteration of local hemodynamics is important (eye diseases, acute kidney injury, cyclosporine nephrotoxicity) as well as future plan for repositioning MR antagonists in ischemic kidney diseases and renal transplantation.