The renal effects of mineralocorticoid receptor antagonists

Abstract

Beyond its well known classic effects on renal water and electrolytes metabolism, an increasing amount of experimental and clinical evidence suggests that aldosterone contributes to the pathogenesis and progression of kidney disease. The binding of aldosterone on epithelial and non-epithelial cells of the kidney induces many deleterious effects, such as podocyte apoptosis and injury, mesangial cell proliferation and deformability and tubulointerstitial inflammation, finally resulting in glomerular fibrosis and sclerosis. Moreover, aldosterone acting by fast non-genomic mechanisms, may induce other potential deleterious effects on kidney function and structure. Indeed, many experimental studies have shown that aldosterone participates to the progression of kidney disease through hemodynamic and direct cellular actions and that antagonists of aldosterone may retard the progression of kidney disease, independently of effects on blood pressure. Therefore, blockade of the aldosterone pathway may prove to be a beneficial therapy for kidney disease. In this brief review we summarize the reported data that support an independent role of aldosterone in inducing kidney damage both in human and experimental models, and interventional studies that highlight how strategies aimed to antagonize its action may favorably modify the progressive decline of renal function in patient with kidney disease and in patients with extrarenal disease frequently associated with kidney function impairment.

Keywords: Chronic kidney disease; Glomerular filtration rate; Hyperkalemia; Mineralocorticoid receptor antagonists; Proteinuria.