1. ¹Department of Nephrology, University Hospital Coventry and Warwickshire NHS Trust, Coventry, UK
2. ²Warwick Medical School, The University of Warwick, Coventry, UK
3. ³Clinical Endocrinology, Charité Campus Mitte, Charité University Medicine Berlin, Berlin, Germany
4. ⁴Renal Unit, University Hospital Birmingham NHS Trust, Birmingham, UK
5. ⁵Biological Sciences, The University of Warwick, Coventry, UK
6. ⁶Division of Medical Sciences, Institute of Biomedical Research, The University of Birmingham, Birmingham, UK
7. ⁷Pathology, University College London, London, UK
8. ⁸Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, Los Angeles, California, USA

Correspondence: Daniel Zehnder, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Clifford Bridge Road, Coventry CV2 2DX, UK. E-mail: d.zehnder@warwick.ac.uk

Received 6 August 2007; Revised 2 July 2008; Accepted 15 July 2008; Published online 10 September 2008.

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-1-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-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.