gms | German Medical Science

29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Hochdruckliga e. V. DHL ® - Deutsche Hypertonie Gesellschaft Deutsches Kompetenzzentrum Bluthochdruck

23. bis 25.11.2005, Berlin

Activation of the mineralocorticoid receptor (MR) pathway is associated with an inflammatory response in renal biopsies of patients with severe proteinuria

Die Aktivierung des Mineralokortikoidrezeptors in Nierenbiopsien von Patienten mit schwerer Proteinurie ist assoziiert mit einer gesteigerten inflammatorischen Antwort

Meeting Abstract

  • M.O. Quinkler - Charité Campus Mitte, Berlin (Berlin, D)
  • D. Zehnder - University of Birmingham, Queen Elizabeth Hospital (Birmingham, GB)
  • J. Lepenies - University of Birmingham, Queen Elizabeth Hospital (Birmingham, GB)
  • A. Howie - University of Birmingham, Queen Elizabeth Hospital (Birmingham, GB)
  • M. Hewison - University of Birmingham, Queen Elizabeth Hospital (Birmingham, GB)
  • P.M. Stewart - University of Birmingham, Queen Elizabeth Hospital (Birmingham, GB)

Hypertonie 2005. 29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Berlin, 23.-25.11.2005. Düsseldorf, Köln: German Medical Science; 2006. Doc05hochP10

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hoch2005/05hoch010.shtml

Veröffentlicht: 8. August 2006

© 2006 Quinkler et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Aldosterone (A) has been emerged as a deleterious hormone in the heart, and MR blockade by spironolactone reduces morbidity in patients with heart failure. There is evidence that A contributes also to the development of renal fibrosis in several rat models. Investigations of the role of A in clinical renal disease are very rare and nothing is known about renal MR expression and MR effector mechanisms.

We quantified MR and sgk1 as well as mRNA expression of inflammatory mediators such as macrophage chemoattractant protein 1 (MCP1), transforming growth factor beta1 (TGF-beta1), and interleukin-6 (IL-6) using TaqMan real-time PCR in 95 kidney biopsies from patients undergoing kidney biopsy. Serum and 24h-urine samples were used to document renal function, endocrine parameters and MCP1 protein excretion. Renal fibrosis was assessed by periodic acid-methenamine silver staining. Biopsies were stained for CD68 (macrophages), CD34 (endothelium) and MR using IHC.

Serum A significantly (p<0.01) negatively correlated with creatinine clearance and positively (p<0.05) with renal scarring, but not with MR mRNA expression. Patients with severe albuminuria (>2g/24h, n=15) had the highest renal scarring and the lowest epithelial CD34 staining. This group showed a significant increase in MR (5-fold), in sgk1 (2.5-fold) and in inflammatory mediators (7-fold of MCP1, 3-fold of TGFbeta1 and 2-fold of IL-6 mRNA expression). Urinary MCP1 protein excretion was significantly increased in patients with severe albuminuria and resulted in an increased macrophage invasion.

For the first time we investigated the expression of MR and sgk1 as well as of inflammatory mediators in human kidney. In patients with severe proteinuria, MR and sgk1 expression are significantly upregulated, suggesting a direct receptor-mediated activation of mineralocorticoid action. The activation of the MR signalling pathway seems to be associated with the inflammatory response in renal diseases