title: The selective mineralocorticoid receptor antagonist eplerenone is protective in mild anti-GBM glomeru-lonephritis.
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 membrane (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.
  
  
  CONCLUSIONS
  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.
authors: Department of Nephrology and Dialysis, Academic Teaching Hospital Feldkirch, Feldkirch, Austria.
authors: Emanuel
authors: E
authors: Zitt
authors: Kathrin
authors: K
authors: Eller
authors: Julia M
authors: JM
authors: Huber
authors: Alexander H
authors: AH
authors: Kirsch
authors: Andrea
authors: A
authors: Tagwerker
authors: Gert
authors: G
authors: Mayer
authors: Alexander R
authors: AR
authors: Rosenkranz
mesh_terms: D000419:Albuminuria; D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D000077545:Eplerenone; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D011817:Rabbits; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013154:Spleen / Q000187:drug effects / Q000378:metabolism
chemical_list: D016207:Cytokines; D007074:Immunoglobulin G; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone