title: urinary biomarkers in relapsing antineutrophil cytoplasmic antibody-associated vasculitis.
abstract: OBJECTIVE
  Glomerulonephritis (GN) is common in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but tools for early detection of renal involvement are imperfect. We investigated 4 urinary proteins as markers of active renal AAV: alpha-1 acid glycoprotein (AGP), kidney injury molecule-1 (KIM-1), monocyte chemoattractant protein-1 (MCP-1), and neutrophil gelatinase-associated lipocalin (NGAL).
  
  
  METHODS
  Patients with active renal AAV (n = 20), active nonrenal AAV (n = 16), and AAV in longterm remission (n = 14) were identified within a longitudinal cohort. Urinary biomarker concentrations (by ELISA) were normalized for urine creatinine. Marker levels during active AAV were compared to baseline remission levels (from 1-4 visits) for each patient. Areas under receiver-operating characteristic curves (AUC), sensitivities, specificities, and likelihood ratios (LR) comparing disease states were calculated.
  
  
  RESULTS
  Baseline biomarker levels varied among patients. All 4 markers increased during renal flares (p < 0.05). MCP-1 discriminated best between active renal disease and remission: a 1.3-fold increase in MCP-1 had 94% sensitivity and 89% specificity for active renal disease (AUC = 0.93, positive LR 8.5, negative LR 0.07). Increased MCP-1 also characterized 50% of apparently nonrenal flares. Change in AGP, KIM-1, or NGAL showed more modest ability to distinguish active renal disease from remission (AUC 0.71-0.75). Hematuria was noted in 83% of active renal episodes, but also 43% of nonrenal flares and 25% of remission samples.
  
  
  CONCLUSIONS
  Either urinary MCP-1 is not specific for GN in AAV, or it identifies early GN not detected by standard assessment and thus has potential to improve care. A followup study with kidney biopsy as the gold standard is needed.
authors.affiliation: Department of Medicine, Section of Rheumatology, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Jason G
authors.initials: JG
authors.lastname: Lieberthal
authors.forename: David
authors.initials: D
authors.lastname: Cuthbertson
authors.forename: Simon
authors.initials: S
authors.lastname: Carette
authors.forename: Gary S
authors.initials: GS
authors.lastname: Hoffman
authors.forename: Nader A
authors.initials: NA
authors.lastname: Khalidi
authors.forename: Curry L
authors.initials: CL
authors.lastname: Koening
authors.forename: Carol A
authors.initials: CA
authors.lastname: Langford
authors.forename: Kathleen
authors.initials: K
authors.lastname: Maksimowicz-McKinnon
authors.forename: Philip
authors.initials: P
authors.lastname: Seo
authors.forename: Ulrich
authors.initials: U
authors.lastname: Specks
authors.forename: Steven R
authors.initials: SR
authors.lastname: Ytterberg
authors.forename: Peter A
authors.initials: PA
authors.lastname: Merkel
authors.forename: Paul A
authors.initials: PA
authors.lastname: Monach
mesh_terms: D000209:Acute-Phase Proteins / Q000652:urine; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000150:complications / Q000175:diagnosis* / Q000652:urine; D015415:Biomarkers / Q000652:urine*; D018932:Chemokine CCL2 / Q000652:urine; D005260:Female; D005921:Glomerulonephritis / Q000175:diagnosis* / Q000209:etiology / Q000652:urine; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008297:Male; D008562:Membrane Glycoproteins / Q000652:urine; D008875:Middle Aged; D009961:Orosomucoid / Q000652:urine; D011237:Predictive Value of Tests; D011518:Proto-Oncogene Proteins / Q000652:urine; D012372:ROC Curve; D011991:Receptors, Virus; D012008:Recurrence; D013997:Time Factors; D055815:Young Adult
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D018932:Chemokine CCL2; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D008562:Membrane Glycoproteins; D009961:Orosomucoid; D011518:Proto-Oncogene Proteins; D011991:Receptors, Virus
keywords: BIOMARKERS; GLOMERULONEPHRITIS; MONOCYTE CHEMOATTRACTANT PROTEIN-1; VASCULITIS; WEGENER GRANULOMATOSIS
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