Zehnder, Daniel, Quinkler, Marcus, Eardley, Kevin S., Bland, Rosemary, Lepenies, Julia, Hughes, Susan V., Raymond, Neil T., Howie, Alexander J., Cockwell, Paul, Stewart, Paul M. (Paul Michael), 1959- and Hewison, Martin. (2008) Reduction of the vitamin D hormonal system in kidney disease is associated with increased renal inflammation. Kidney International, Vol.74 (No.10). pp. 1343-1353. ISSN 0085-2538

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Abstract

To examine any potential role for 1,25-dihydroxyvitamin D (1,25(OH)2D) in inflammation associated with chronic kidney disease we measured vitamin D metabolites, markers of inflammation and gene expression in 174 patients with a variety of kidney diseases. Urinary MCP-1 protein and renal macrophage infiltration were each significantly but inversely correlated with serum 1,25(OH)2D levels. Logistic regression analysis with urinary MCP-1 as binary outcome showed that a 10-unit increase in serum 1,25(OH)2D or 25OHD resulted in lower renal inflammation. Analysis of 111 renal biopsies found that renal injury was not associated with a compensatory increase in mRNA for the vitamin D-activating enzyme 25-hydroxyvitamin D-1α-hydroxylase (CYP27B1), its catabolic counterpart 24-hydroxylase, or the vitamin D receptor. There was, however, a significant association between tissue MCP-1 and CYP27B1. Patients with acute renal inflammation had a significant increase in urinary and tissue MCP-1, macrophage infiltration, and macrophage and renal epithelial CYP27B1 expression but significantly lower levels of serum 1,25(OH)2D in comparison to patients with chronic ischemic disease despite similar levels of renal damage. In vitro, 1,25(OH)2D attenuated TNFα-induced MCP-1 expression by human proximal tubule cells. Our study indicates that renal inflammation is associated with decreased serum vitamin D metabolites and involves activation of the paracrine/autocrine vitamin D system.

Item Type:	Journal Article
Subjects:	Q Science > QP Physiology R Medicine > RC Internal medicine
Divisions:	Faculty of Medicine > Warwick Medical School > Health Sciences Faculty of Medicine > Warwick Medical School > Translational & Systems Medicine > Metabolic and Vascular Health Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Kidneys -- Diseases , Vitamin D in the body, Kidneys -- Metabolism
Journal or Publication Title:	Kidney International
Publisher:	Nature Publishing Group
ISSN:	0085-2538
Official Date:	November 2008
Volume:	Vol.74
Number:	No.10
Page Range:	pp. 1343-1353
Identification Number:	10.1038/ki.2008.453
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Funder:	Foundation for Nephrology, National Institutes of Health (U.S.) (NIH)
Grant number:	R01AI076292 (NIH)
URI:	http://wrap.warwick.ac.uk/id/eprint/37093

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