Reduction of the vitamin D hormonal system in kidney disease is associated with increased renal inflammation.
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-1alpha-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 TNFalpha-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.
Zehnder
Daniel
D
Department of Nephrology, University Hospital Coventry and Warwickshire NHS Trust, Coventry, UK. mail: d.zehnder@warwick.ac.uk
Quinkler
Marcus
M
Eardley
Kevin S
KS
Bland
Rosemary
R
Lepenies
Julia
J
Hughes
Susan V
SV
Raymond
Neil T
NT
Howie
Alexander J
AJ
Cockwell
Paul
P
Stewart
Paul M
PM
Hewison
Martin
M
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019898:Autocrine Communication; D018932:Chemokine CCL2 / Q000032:analysis; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D007674:Kidney Diseases / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D019899:Paracrine Communication; D012333:RNA, Messenger / Q000032:analysis; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood* / Q000378:metabolism; D055815:Young Adult
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D012333:RNA, Messenger; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase
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