Abstract | BACKGROUND: METHODS AND RESULTS: We quantified MR, serum- and glucocorticoid-regulated kinase 1 (sgk1), and mRNA expression of inflammatory mediators such as macrophage chemoattractant protein-1 (MCP-1), transforming growth factor-beta1, and interleukin-6 in 95 human kidney biopsies in patients with renal failure and mild to marked proteinuria of diverse etiologic origins. We measured renal function, serum aldosterone, urinary MCP-1 protein excretion, and the amount of chronic renal damage. Macrophage invasion was quantified by CD68 and vascularization by CD34 immunostaining. Serum aldosterone correlated negatively with creatinine clearance (P<0.01) and positively with renal scarring (P<0.05) but did not correlate with MR mRNA expression or proteinuria. Patients with heavy albuminuria (>2 g/24 h; n=15) had the most renal scarring and the lowest endothelial CD34 staining. This group showed a significant 5-fold increase in MR, a 2.5-fold increase in sgk1 expression and a significant increase in inflammatory mediators (7-fold increase in MCP-1, 3-fold increase in transforming growth factor-beta1, and 2-fold increase in interleukin-6 mRNA). Urinary MCP-1 protein excretion and renal macrophage invasion were significantly increased in patients with heavy albuminuria. CONCLUSIONS: These studies support animal data linking aldosterone/MR activation to renal inflammation and proteinuria. Further studies are urgently required to assess the potential beneficial effects of MR antagonism in patients with renal disease.
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Authors | Marcus Quinkler, Daniel Zehnder, Kevin S Eardley, Julia Lepenies, Alexander J Howie, Susan V Hughes, Paul Cockwell, Martin Hewison, Paul M Stewart |
Journal | Circulation
(Circulation)
Vol. 112
Issue 10
Pg. 1435-43
(Sep 06 2005)
ISSN: 1524-4539 [Electronic] United States |
PMID | 16145013
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- CCL2 protein, human
- Chemokine CCL2
- Immediate-Early Proteins
- Interleukin-6
- RNA, Messenger
- Receptors, Mineralocorticoid
- TGFB1 protein, human
- Transforming Growth Factor beta
- Transforming Growth Factor beta1
- Aldosterone
- Protein Serine-Threonine Kinases
- serum-glucocorticoid regulated kinase
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Topics |
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Aldosterone
(blood)
- Biopsy
- Blood Pressure
- Chemokine CCL2
(genetics)
- Female
- Glomerular Basement Membrane
(pathology)
- Humans
- Immediate-Early Proteins
(genetics)
- Interleukin-6
(genetics)
- Ischemia
(immunology, pathology, physiopathology)
- Kidney
(pathology, physiology)
- Kidney Function Tests
- Male
- Middle Aged
- Protein Serine-Threonine Kinases
(genetics)
- Proteinuria
(immunology, pathology, physiopathology)
- RNA, Messenger
(analysis)
- Receptors, Mineralocorticoid
(genetics)
- Transforming Growth Factor beta
(genetics)
- Transforming Growth Factor beta1
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