Aldosterone-induced fibrosis in the kidney: questions and controversies.

Over the years, aldosterone has been a favorite topic of renal physiologists given its role in the maintenance of body fluids. Investigators only recently are coming to appreciate a second proinflammatory and profibrotic role for this hormone. Mineralocorticoids such as aldosterone trigger a profibrotic process that in many respects mimics the early phase of wound healing. Depending on the type of cell involved, aldosterone may activate the profibrotic process through classic mineralocorticoid receptors, nonclassic membrane-associated mineralocorticoid receptors, and/or glucocorticoid receptors. In the kidney, the actions of aldosterone can be attenuated by 11-dehydro metabolites of endogenous glucocorticoids generated by isoforms of the enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD-1 and 11β-HSD-2). Thus, the renal 11β-HSD isoforms may have 2 functions: to block the improper activation of mineralocorticoid receptors by binding endogenous glucocorticoids and to synthesize agents that limit the actions of aldosterone. Although sodium in the diet has been implicated in aggravating aldosterone-induced renal fibrotic processes, preliminary findings are consistent with the view that aldosterone alone can initiate matrix production in renal tissue even in the absence of active sodium transport. Thus, there is a growing body of laboratory and clinical evidence supporting the use of inhibitors of aldosterone action in patients with both glomerular and tubular diseases.