title: Urinary monocyte chemoattractant protein-1 (MCP-1) is a marker of active renal vasculitis.
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.
authors.affiliation: Renal Section, Division of Medicine, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK. f.tam@imperial.ac.uk
authors.forename: Frederick W K
authors.initials: FW
authors.lastname: Tam
authors.forename: Jan-Stephan
authors.initials: JS
authors.lastname: Sanders
authors.forename: Abraham
authors.initials: A
authors.lastname: George
authors.forename: Tarig
authors.initials: T
authors.lastname: Hammad
authors.forename: Caroline
authors.initials: C
authors.lastname: Miller
authors.forename: Tammy
authors.initials: T
authors.lastname: Dougan
authors.forename: H Terence
authors.initials: HT
authors.lastname: Cook
authors.forename: Cees G M
authors.initials: CG
authors.lastname: Kallenberg
authors.forename: Gill
authors.initials: G
authors.lastname: Gaskin
authors.forename: Jeremy B
authors.initials: JB
authors.lastname: Levy
authors.forename: Charles D
authors.initials: CD
authors.lastname: Pusey
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000652:urine*; D018932:Chemokine CCL2 / Q000097:blood / Q000652:urine*; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000652:urine*; D005260:Female; D005921:Glomerulonephritis / Q000473:pathology; D006801:Humans; D007674:Kidney Diseases / Q000652:urine*; D008297:Male; D008565:Membrane Proteins / Q000652:urine*; D008875:Middle Aged; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D014657:Vasculitis / Q000652:urine*
chemical_list: D015415:Biomarkers; C111835:CCL2 protein, human; C515538:CX3CL1 protein, human; D018932:Chemokine CCL2; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D008565:Membrane Proteins