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Int J Clin Exp Pathol 2011;4(6):606-615
Original Article
The selective mineralocorticoid receptor antagonist eplerenone is protective in mild anti-
GBM glomerulonephritis
Emanuel Zitt, Kathrin Eller, Julia M. Huber, Alexander H. Kirsch, Andrea Tagwerker, Gert Mayer, Alexander R. Rosenkranz
Department of Nephrology and Dialysis, Academic Teaching Hospital Feldkirch, Feldkirch, Austria; Department of Internal Medicine, Clinical
Division of Nephrology, Medical University of Graz, Graz, Austria; Department of Internal Medicine IV, Nephrology and Hypertension, Innsbruck
Medical University, Innsbruck, Austria.
Received July 25, 2011; accepted August 2, 2011; Epub August 3; published August 15, 2011
Abstract: Background: Growing evidence suggests that blockade of the aldosterone-receptor may preserve kidney function by anti-
inflammatory effects independent of the blood pressure. We hypothesized that the selective aldosterone-receptor antagonist eplerenone has a
profound anti-inflammatory effect in the autologous phase of anti-glomerular basement (GBM) glomerulonephritis (GN). Methods: Mice
received ≈200mg/kg body wt/day eplerenone via supplemented chow diet or standard chow starting at the day of immunization with rabbit IgG.
Three days later the anti-GBM antibody was injected and the experiments were stopped at day 7 and 14. Results: Mice receiving eplerenone
showed significantly decreased albuminuria and glomerular sclerosis at day 7 and 14 after induction of anti-GBM GN. Eplerenone treatment
significantly inhibited the infiltration of CD4+, CD8+ T cells and macrophages into the kidneys. Circulating levels and glomerular deposition of
autologous IgG were comparable in both groups. At day 7 the pro-inflammatory cytokines MCP-1 and IL-6 were found to be significantly
decreased in regional draining lymph nodes of eplerenone-treated mice, whereas the anti-inflammatory cytokine IL-10 was significantly
upregulated. In line, splenocytes from eplerenone-treated nephritic mice produced significantly increased IL-10. Conclusion: Aldosterone-
receptor blockade by eplerenone effectively attenuated proteinuria, kidney damage and the inflammatory response in anti-GBM GN by
significantly decreasing pro-inflammatory cytokines in the regional draining lymph nodes of the kidney. Our results suggest that this selective
aldosterone receptor antagonist is a possible additional tool in the treatment of GN. (IJCEP1107004).
Keywords: Aldosterone antagonism, glomerulonephritis, eplerenone, renal inflammation
Full text PDF
Address all correspondence to:
Dr. Alexander R Rosenkranz
Universitätsklinik für Innere Medizin
Klinische Abteilung für Nephrologie
Auenbruggerplatz 27, A-8036 Graz, Austria
Tel: +43-316-385-12170
Fax: +43-316-385-14426
E-mail: alexander.rosenkranz@medunigraz.at
Original Article
The selective mineralocorticoid receptor antagonist eplerenone is protective in mild anti-
GBM glomerulonephritis
Emanuel Zitt, Kathrin Eller, Julia M. Huber, Alexander H. Kirsch, Andrea Tagwerker, Gert Mayer, Alexander R. Rosenkranz
Department of Nephrology and Dialysis, Academic Teaching Hospital Feldkirch, Feldkirch, Austria; Department of Internal Medicine, Clinical
Division of Nephrology, Medical University of Graz, Graz, Austria; Department of Internal Medicine IV, Nephrology and Hypertension, Innsbruck
Medical University, Innsbruck, Austria.
Received July 25, 2011; accepted August 2, 2011; Epub August 3; published August 15, 2011
Abstract: Background: Growing evidence suggests that blockade of the aldosterone-receptor may preserve kidney function by anti-
inflammatory effects independent of the blood pressure. We hypothesized that the selective aldosterone-receptor antagonist eplerenone has a
profound anti-inflammatory effect in the autologous phase of anti-glomerular basement (GBM) glomerulonephritis (GN). Methods: Mice
received ≈200mg/kg body wt/day eplerenone via supplemented chow diet or standard chow starting at the day of immunization with rabbit IgG.
Three days later the anti-GBM antibody was injected and the experiments were stopped at day 7 and 14. Results: Mice receiving eplerenone
showed significantly decreased albuminuria and glomerular sclerosis at day 7 and 14 after induction of anti-GBM GN. Eplerenone treatment
significantly inhibited the infiltration of CD4+, CD8+ T cells and macrophages into the kidneys. Circulating levels and glomerular deposition of
autologous IgG were comparable in both groups. At day 7 the pro-inflammatory cytokines MCP-1 and IL-6 were found to be significantly
decreased in regional draining lymph nodes of eplerenone-treated mice, whereas the anti-inflammatory cytokine IL-10 was significantly
upregulated. In line, splenocytes from eplerenone-treated nephritic mice produced significantly increased IL-10. Conclusion: Aldosterone-
receptor blockade by eplerenone effectively attenuated proteinuria, kidney damage and the inflammatory response in anti-GBM GN by
significantly decreasing pro-inflammatory cytokines in the regional draining lymph nodes of the kidney. Our results suggest that this selective
aldosterone receptor antagonist is a possible additional tool in the treatment of GN. (IJCEP1107004).
Keywords: Aldosterone antagonism, glomerulonephritis, eplerenone, renal inflammation
Full text PDF
Address all correspondence to:
Dr. Alexander R Rosenkranz
Universitätsklinik für Innere Medizin
Klinische Abteilung für Nephrologie
Auenbruggerplatz 27, A-8036 Graz, Austria
Tel: +43-316-385-12170
Fax: +43-316-385-14426
E-mail: alexander.rosenkranz@medunigraz.at
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