Clinical and Experimental Nephrology

, Volume 12, Issue 4, pp 233–242

Aldosterone and glomerular podocyte injury

Review Article

DOI: 10.1007/s10157-008-0034-9

Cite this article as:
Nagase, M. & Fujita, T. Clin Exp Nephrol (2008) 12: 233. doi:10.1007/s10157-008-0034-9

Abstract

Aldosterone is traditionally viewed as a hormone regulating electrolyte and blood pressure homeostasis by acting on the distal nephron. Accumulating evidence suggests that aldosterone also plays pathogenetic roles in cardiovascular and renal injury. For example, aldosterone is a potent inducer of proteinuria. We demonstrated that podocyte injury underlies the pathogenesis of proteinuria in aldosterone-infused rats on a high salt diet. Mineralocorticoid receptor was detected in the podocytes in vivo and in vitro, and aldosterone caused induction of its effector kinase Sgk1, activation of NADPH oxidase and generation of reactive oxygen species. Selective aldosterone blocker eplerenone, as well as antioxidant tempol, ameliorated aldosterone-induced podocyte injury and proteinuria. Aldosterone was also involved in the podocyte damage and proteinuria of metabolic syndrome model SHR/NDmcr-cp. Adipocyte-derived aldosterone releasing factors were suggested to contribute to the aldosterone excess of this model. Furthermore, high salt diet markedly worsened the renal injury of SHR/NDmcr-cp. Although salt lowered serum aldosterone levels, it caused MR activation in the kidney. Accordingly, eplerenone dramatically improved the salt-evoked nephropathy. Taken together, aldosterone blockers can be an excellent therapeutic strategy for the treatment of podocyte injury, proteinuria, and cardiovascular and renal complications, not only in high aldosterone states but also in patients with activated MR signaling in the target tissue, whose circulating aldosterone level is not necessarily high. Addition of aldosterone blockers in patients treated with ACEIs or ARBs are also promising, because of “aldosterone breakthrough” phenomenon. Careful monitoring of hyperkalemia is necessary, especially in patients with impaired renal function.

Keywords

Proteinuria Chronic kidney disease Metabolic syndrome Oxidative stress Salt Mineralocorticoid receptor activation Aldosterone releasing factors 

Copyright information

© Japanese Society of Nephrology 2008

Authors and Affiliations

  1. 1.Department of Nephrology and EndocrinologyUniversity of Tokyo Graduate School of MedicineTokyoJapan

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