Urinary biomarkers in relapsing antineutrophil cytoplasmic antibody-associated vasculitis

Jason G. Lieberthal, David Cuthbertson, Simon Carette, Gary S. Hoffman, Nader A. Khalidi, Curry L. Koening, Carol A. Langford, Kathleen Maksimowicz-McKinnon, Philip Seo, Ulrich Specks, Steven R. Ytterberg, Peter A. Merkel, Paul A. Monach

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28 Scopus citations

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. Conclusion. 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. The Journal of Rheumatology

Original languageEnglish (US)
Pages (from-to)674-683
Number of pages10
JournalJournal of Rheumatology
Volume40
Issue number5
DOIs
StatePublished - May 2013

Keywords

  • Biomarkers
  • Glomerulonephritis
  • Monocyte chemoattractant protein-1
  • Vasculitis
  • Wegener granulomatosis

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

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    Lieberthal, J. G., Cuthbertson, D., Carette, S., Hoffman, G. S., Khalidi, N. A., Koening, C. L., Langford, C. A., Maksimowicz-McKinnon, K., Seo, P., Specks, U., Ytterberg, S. R., Merkel, P. A., & Monach, P. A. (2013). Urinary biomarkers in relapsing antineutrophil cytoplasmic antibody-associated vasculitis. Journal of Rheumatology, 40(5), 674-683. https://doi.org/10.3899/jrheum.120879