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. 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 prognostic significance of the Birmingham Vasculitis Activity Score (BVAS) with systemic vasculitis patients transferred to the intensive care unit (ICU)

“…The C-X-C motif chemokine 13 (CXCL13) also known as B lymphocyte chemoattractant (BLC), the matrix metalloproteinase-3 (MMP-3), and TIMP metallopeptidase inhibitor 1 (TIMP-1) are the best-performing markers in discriminating active disease from remission, even if compared with reactive protein C (CPR) and erythrocyte sedimentation rate (ESR). [23] Additional potential biomarkers in patients with vasculitides are represented by monocyte chemoattractant protein-1 (MCP-1), [24] the von Willebrand factor antigen, [25] the Pentraxin-3 (PTX3), [26] and the Eotaxin-3. [27,28] A summary of the main studies focused on possible biomarkers in patients with vasculitides is reported in Table 5.…”

Biomarkers in vasculitis

“…The presence of significant proteinuria is an important marker for staging and prognosis in Henoch-Schoenlein purpura and is often used to make decisions regarding treatment. However, once kidney damage has occurred due to GN, proteinuria, hematuria, and even red blood cell casts may persist without evidence of progressive kidney disease [4,5], so the high sensitivity and specificity of different aspects of urinalysis are apparent only during the first episode of GN. Discovery of urinary markers of active kidney damage would appear to be plausible [5-7], but such markers have not reached clinical use in vasculitis.…”

The Relationship of McP-1 and Tubulointerstitial Fibrosis in Chronic Glomerulonephritis

“…Связывание МСР-1 с CCR2 сопровождается как моноцитарной инфильтрацией, так и пролиферацией эпителиальных, эндотелиальных и сосудистых гладкомышечных клеток. Участие MCP-1 в воспалительном процессе в почечной паренхиме, а значит и в ремоделировании почечной ткани подтверждается тем, что уровень МСР-1 в моче повышается в период обострения гломерулонефрита как в первичном [5], так и вторичном его варианте, например, при системной красной волчанке [6] и системных васкулитах [7]. Важной морфологической особенностью является то, что при пролиферативных формах гломерулонефритов уровень МСР в моче был выше, чем при непролиферативных формах [8].…”