Mineralocorticoid receptor activation as an etiological factor in kidney diseases.

Ueda, Kohei; Nagase, Miki

The mineralocorticoid receptor (MR) is a member of the steroid-responsive nuclear receptor family. Currently, in addition to its classical role in fluid homeostasis, attention has been focused on the pro-proteinuric and pro-inflammatory effects of MR in renal and cardiovascular diseases. Since proteinuria has been shown to be an important factor in the prognosis of patients with chronic kidney disease (CKD) [according to the newest Japanese Society of Nephrology and Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for the treatment of CKD], it is worth discussing the role of MR in the progression of proteinuric CKD and the possible association with podocyte injury. Rac1, a Rho-GTPase family protein, is known for its role in the regulation of the cytoskeleton. We discovered the role of active Rac1 in amplifying MR activation in one of our studies and then continued to study how the Rac1−MR pathway contributes to the progression of kidney diseases. We then discovered the harmful effects of the activation of the Rac1−MR pathway in response to salt loading in the kidney for proteinuric kidney diseases of various animal models with salt-sensitive hypertension, such as Dahl salt-sensitive rats, RhoGDIα-knockout mice, angiotensin II-overproducing mice, and aldosterone-infused rats. In this review, we have introduced recent findings that suggest the contribution of MR activation to kidney diseases and the role of the Rac1−MR pathway in kidney injury associated with salt-sensitive hypertension and proteinuria. Thus, the Rac1−MR pathway is a potential therapeutic target in patients with proteinuric CKD.

MINERALOCORTICOID receptors; ETIOLOGY of kidney diseases; NUCLEAR receptors (Biochemistry); STEROIDS; HOMEOSTASIS; INFLAMMATION; CARDIOVASCULAR diseases; PROTEINURIA

Clinical & Experimental Nephrology, 2014, Vol 18, Issue 1, p16

1342-1751

Academic Journal

10.1007/s10157-013-0827-3