NR3C2 and chronic kidney disease: Mineralocorticoid receptor can also be activated by cortisol.46 Under normal circumstances, aldosterone is co-expressed with the enzyme 11-beta-hydroxysteroid dehydrogenase-2 (11β-HSD2), which inactivates cortisol in the kidneys.47 However, under certain circumstances such as visceral obesity, hypertension, heart failure (HF), and/or CKD, cortisol may become available to activate the MR due to the down-regulation of 11β-HSD2, potentially leading to inflammation and fibrosis in the kidneys.40,48,49