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The role of capillary density, macrophage infiltration and interstitial scarring in the pathogenesis of human chronic kidney disease
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Eardley, Kevin S., Kubal, Chandrashekhar, Zehnder, Daniel, Quinkler, Marcus, Lepenies, Julia, Savage, Caroline O. S., Howie, Alexander J., Kaur, Kirrenjit, Cooper, Mark S., Adu, Dwomoa and Cockwell, Paul (2008) The role of capillary density, macrophage infiltration and interstitial scarring in the pathogenesis of human chronic kidney disease. Kidney International, Volume 74 (Number 4). pp. 495-504. doi:10.1038/ki.2008.183 ISSN 0085-2538.
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Official URL: http://dx.doi.org/10.1038/ki.2008.183
Abstract
To assess the relationship between interstitial capillary density and interstitial macrophages we prospectively measured these factors in situ in 110 patients with chronic kidney disease. Macrophage numbers and urinary MCP-1/CCL2 levels significantly correlated inversely with capillary density which itself significantly correlated inversely with chronic damage and predicted disease progression. In 54 patients with less than 20% chronic damage, there was a significant correlation between the urinary albumin to creatinine ratio and MCP-1/CCL2, and MCP-1/CCL2 and macrophages but not between MCP-1/CCL2 and capillary density. Conversely, in 56 patients with over 20% chronic damage there was no correlation between MCP-1/CCL2 and macrophages but there were significant inverse correlations between capillary density and both macrophages and chronic damage. The expression of VEGF mRNA significantly correlated with macrophage infiltration, capillary density and chronic scarring. In an ischemic-hypertensive subgroup there was upregulation of the hypoxia marker carbonic anhydrase IX and with over 20% chronic damage an increased macrophage to CCR2 ratio. Our study shows that proteinuria and MCP-1/CCL2 are important for macrophage recruitment in early disease. As renal scarring evolves, alternative pathways relating to progressive tissue ischemia secondary to obliteration of the interstitial capillary bed predominate.
Item Type: | Journal Article | ||||
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Subjects: | Q Science > QP Physiology Q Science > QR Microbiology > QR180 Immunology R Medicine > RC Internal medicine |
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Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Library of Congress Subject Headings (LCSH): | Capillaries, Macrophages, Anoxemia, Kidneys -- Diseases, Vascular endothelial growth factors, Chemokines -- Immunology | ||||
Journal or Publication Title: | Kidney International | ||||
Publisher: | Nature Publishing Group | ||||
ISSN: | 0085-2538 | ||||
Official Date: | August 2008 | ||||
Dates: |
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Volume: | Volume 74 | ||||
Number: | Number 4 | ||||
Number of Pages: | 10 | ||||
Page Range: | pp. 495-504 | ||||
DOI: | 10.1038/ki.2008.183 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Restricted or Subscription Access |
Data sourced from Thomson Reuters' Web of Knowledge
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