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NDT Advance Access published online on September 7, 2004
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfh487
© 2004 by European Renal Association - European Dialysis and Transplant Association
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Received March 19, 2004
Accepted July 30, 2004

Original Articles

Urinary monocyte chemoattractant protein-1 (MCP-1) is a marker of active renal vasculitis

Frederick W. K. Tam 1*, Jan-Stephan Sanders 1, Abraham George 1, Tarig Hammad 1, Caroline Miller 2, Tammy Dougan 1, H. Terence Cook 3, Cees G. M. Kallenberg 4, Gill Gaskin 1, Jeremy B. Levy 1, and Charles D. Pusey 1

1 Renal Section, Division of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK
2 Department of Histopathology, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK; Department of Pathology, HSW451, 513 Parnassus Avenue, University of California, San Francisco, CA 94143, USA
3 Department of Histopathology, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK
4 Department of Clinical Immunology, University Hospital Groningen, The Netherlands

* To whom correspondence should be addressed. E-mail: f.tam{at}imperial.ac.uk.



  Abstract

Background. Macrophage infiltration and cytokine production are important in the pathogenesis of crescentic glomerulonephritis in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis. The aim of this study was to investigate whether urinary levels of chemokines, monocyte chemoattractant protein-1 (MCP-1) and fractalkine, were useful tools for non-invasive assessment of renal vasculitis.

Methods. In a prospective study, concentrations of chemokines were measured in urine and serum samples using specific enzyme-linked immunosorbent assays, and related to the patients' clinical status. Renal expression of MCP-1 was studied by immunohistochemical staining of renal biopsies.

Results. Urinary levels of MCP-1 were significantly higher in patients with active (P<0.01) or persistent (P<0.05) renal vasculitis, in comparison with healthy volunteers, control patients, patients with inactive vasculitis and patients with extra-renal disease only. There were no differences in serum concentrations of MCP-1 between these groups. Reduction in urinary MCP-1 levels following treatment preceded the improvement of renal function by a median of 2 weeks. In one patient, rising urinary levels of MCP-1, despite immunosuppressive therapy, was associated with progression to severe renal failure. There were no differences in urinary fractalkine levels between the different groups of patients and controls. Immunohistology of renal biopsies from patients with crescentic glomerulonephritis showed increased staining for MCP-1 in glomerular and interstitial cells. Urinary MCP-1 levels correlated with glomerular, but not tubulointerstitial, macrophage infiltration (P<0.05).

Conclusions. This study shows that measurement of urinary MCP-1, but not fractalkine, is a useful non-invasive technique for the assessment of renal involvement and monitoring the response to therapy in ANCA-associated vasculitis.

Keywords: ANCA; chemokine; crescent; glomerulonephritis; MCP-1; vasculitis.
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