Mineralocorticoid receptor activation and blockade: an emerging paradigm in chronic kidney disease

被引:109
作者
Bertocchio, Jean-Philippe [1 ]
Warnock, David G. [2 ]
Jaisser, Frederic [1 ]
机构
[1] Ctr Rech Cordeliers, INSERM, U872, Team 1, F-75270 Paris, France
[2] Univ Alabama Birmingham, Dept Med, Div Nephrol, Birmingham, AL 35294 USA
关键词
aldosterone; kidney diseases; mineralocorticoid; proteinuria; receptors; ANGIOTENSIN-ALDOSTERONE SYSTEM; CONVERTING ENZYME-INHIBITOR; CHRONIC RENAL-DISEASE; CHRONIC CYCLOSPORINE NEPHROTOXICITY; CHRONIC-HEMODIALYSIS PATIENTS; LEFT-VENTRICULAR DYSFUNCTION; PLACEBO-CONTROLLED TRIAL; HEART-FAILURE PATIENTS; INDUCED DIABETIC-RATS; BLOOD-PRESSURE;
D O I
10.1038/ki.2011.48
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Slowing the progression of chronic kidney diseases (CKDs) requires new and effective treatment approaches. Aldosterone classically acts on the distal nephron: it facilitates sodium reabsorption, potassium secretion, and participates in blood pressure control. Recently, new targets of aldosterone have been described including the heart and the vasculature, and other kidney cells such as mesangial cells, podocytes, and renal fibroblasts. The pathophysiological implications of increased mineralocorticoid receptor (MR) expression and activation (either dependent on aldosterone or direct ligand-independent activation) and its blockade have been illustrated with ex vivo in cell cultures and in vivo in experimental animal models of CKD, including diabetic and hypertensive nephropathies, and glomerulopathies. The beneficial effects of the MR antagonists are independent of the hypertensive effect of aldosterone, indicating that blocking the activation of the MR may have unique clinical importance. Several studies have reported efficacy and safety studies with spironolactone or eplerenone in patients with kidney diseases. In this review, we discuss the recent results reported in experimental and clinical research in this field, and emphasize the direct activation of the MR that can occur in pathological states associated with CKD, even in the absence of increased circulating levels of aldosterone. Kidney International (2011) 79, 1051-1060; doi:10.1038/ki.2011.48; published online 16 March 2011
引用
收藏
页码:1051 / 1060
页数:10
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