Reduction of the vitamin D hormonal system in kidney disease is associated with increased renal inflammation

D Zehnder, M Quinkler, KS Eardley, R Bland, J Lepenies, Susan Hughes, NT Raymond, AJ Howie, Paul Cockwell, Paul Stewart, M Hewison

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120 Citations (Scopus)


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-1 alpha-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 TNF alpha-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.
Original languageEnglish
Pages (from-to)1343-1353
Number of pages11
JournalKidney International
Issue number10
Publication statusPublished - 1 Nov 2008


  • VDR
  • CYP24A1
  • inflammation
  • CYP27B1
  • vitamin D
  • chronic kidney disease


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