The use of plasma aldosterone and urinary sodium to potassium ratio as translatable quantitative biomarkers of mineralocorticoid receptor antagonism

Background Accumulating evidence supports the role of the mineralocorticoid receptor(MR) in the pathogenesis of diabetic nephropathy. These findings have generated renewed interest in novel MR antagonistswith improved selectivity against other nuclear hormone receptorsand a potentially reduced risk of hyperkalemia. Characterization of novel MR antagonistswarrants establishing translatable biomarkers of activity at the MR receptor. We assessed the translatability of urinary sodium to potassium ratio (Na+/K+) and plasma aldosterone as biomarkers of MR antagonismusing eplerenone(Inspra®), a commercially available MR antagonist. Further we utilized these biomarkers to demonstrate antagonismof MR by PF-03882845, a novel compound.