The mineralocorticoid receptor in chronic kidney disease and type 2 diabetes
A therapeutic target against inflammation and fibrosis
The role of the mineralocorticoid receptor in the pathophysiology of chronic kidney disease in patients with type 2 diabetes
The mineralocorticoid receptor plays an important role in the pathophysiology of chronic kidney disease in type 2 diabetes.1-3 Under normal physiological conditions, through binding of endogenous ligands aldosterone and cortisol, the mineralocorticoid receptor functions primarily as a regulator of diverse biological processes, fluid and electrolyte homeostasis, blood pressure control, as well as tissue repair and remodelling.1,4
Mineralocorticoid receptor expression in various organs and key ligands1-3
1. Whaley-Connell A, et al. Prog Cardiovasc Dis 2010;52:401–409;
2. Jaisser F & Farman N. Pharmacol Rev 2016;68:49–75;
3. Kolkhof P, et al. Handb Exp Pharmacol 2017;243:271–305
4. Agarwal R, et al. Eur Hear J 2020; doi: 10.1093/eurheartj/ehaa736
Physiological functions of the mineralocorticoid receptor
MR, mineralocorticoid receptor
1. Gomez-Sanchez E & Gomez-Sanchez CE. Compr Physiol 2014;4:965–994
2. Hauck JS, et al. Front Physiol 2019;10:1324
Upon ligand-binding, the mineralocorticoid receptor translocates from the cytoplasm to the nucleus and binds as a dimer to hormone-response elements and recruits coregulators, allowing transcription or repression of mineralocorticoid receptor target genes. Under conditions of disease or pathology (including kidney and heart disease, oxidative stress, salt loading and hyperglycaemia),1,8-10 increased activation of the mineralocorticoid receptor, so called mineralocorticoid receptor overactivation, ‘switches’ the principal role of the mineralocorticoid receptor from homeostatic regulator to pathophysiological mediator by promoting oxidative stress, inflammation and fibrosis.1,5,8,10,11
The mineralocorticoid receptor is involved in the regulation of inflammation and fibrosis and fluid and electrolyte homeostasis via differential gene expression.8,12-14
CKD, chronic kidney disease; DNA, deoxyribonucleic acid; MR, mineralocorticoid receptor
1. Bauersachs J, et al. Hypertension 2015;65:257–263
2. Kolkhof P, et al. Handb Exp Pharmacol 2017;243:271–305
3. Buonafine M, et al. Am J Hypertens 2018;31:1165–1174
4. Buglioni A, et al. Hypertension 2015;65:45–53
5. Imai Y, et al. Physiol Rev 2013;93:481–523
6. Yang J & Young MJ. J Mol Endocrinol 2009;43:53–64
7. Alicic RZ, et al. Clin J Am Soc Nephrol 2017;12:2032–2045
8. Afkarian M, et al. J Am Soc Nephrol 2013;24:302–308
