ANCA-associated vasculitis M31.3 M31.7
Conditions
Interventions
Group 1: In our previous work, we established various T cell subsets in urine as biomarkers for ANCA-associated glomerulonephritis (AAV-GN). These biomarkers demonstrated a high degree of accuracy in
urinary C5a, urinary Bb, urinary C5b-9). Biomarkers will be measured at inclusion and subsequently every 6 months to predict the likelihood of relapse within the following 6 months (until at least 10
Sponsors
Charité – Universitätsmedizin Berlin
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: - ANCA-associated vasculitis (GPA or MPA) - PR3-ANCA or MPO-ANCA positive (at any time) - History of renal involvement - Stable remission (BVAS = 0) for at least 6 months, either off maintenance therapy or on maintenance therapy with rituximab or azathioprine - BVAS of 0 (according to BVAS V3, stable hematuria and proteinuria persisting for at least 3 months are considered as 0) - Age: 18 years or older
Exclusion criteria
Exclusion criteria: - Anuria - Chronic bladder diseases - Advanced chronic kidney impairment (GFR < 15 ml/min) - AAV patients receiving Avacopan at the time of study inclusion
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Elevated amounts of urinary CD3+CD4+ T cells predict renal AAV relapses within the subsequent 6 months. Definition of Renal Relapse: =2 renal BVAS elements or =1 renal BVAS element plus decision for treatment intensification Definition of treatment intensification: >5mg increase in Prednisolone or Initiation of novel immunosuppressive drug or Repeat dose of Rituximab earlier than 6 months after last infusion | — |
Secondary
| Measure | Time frame |
|---|---|
| - Prediction of relapses in the 3 months following each measurement - Prediction of relapses in the subsequent 6 months based on combination of ANCA levels and urinary T cell count - Confirmation of the cutoff of urinary T cells (CD3+CD4+ = 500/100ml) for prediction of renal relapse within the subsequent 6 months - Subgroup analysis of PR3-ANCA and MPO-ANCA AAV cases - Independent analysis of ANCA titers and T cells in urine - mGFR slope over 12 months; Delta mGFR between Month 0 and Month 12 - Renal and systemic relapses, initiation of induction therapies - Course of proteinuria and albuminuria, delta proteinuria/albuminuria between Month 0 and Month 12 - Correlations of biomarkers with mGFR slope and intrarenal inflammation - Subgroup analysis based on remission duration (less than or more than 12 months) - Analysis of alternative new biomarkers (sCD25, sCD163, Torque Teno Virus [TTV], Dkk3, CCL2) as well as biomarkers for complement activation (plasma C3, C4, C5a, C5b-9, Bb, CH50, AH50; urinary C5a, urinary Bb, urinary C5b-9) for relapse prediction, cfDNA, proteomics, mRNA - Correlation of TTV viral load with infection rates and severity of infections - Analysis of the oral microbiome in relation to clinical and serological relapses - Subgroup and interaction analysis according to maintenance therapy and immunosuppressive exposure - Alternative definition of relapse: evaluation by three blinded clinicians of all cases with =1 renal BVAS; relapses are defined as at least 2 of 3 clinicians evaluate as relapse Definition of non-renal Relapse: =1 non-renal BVAS item in combination with treatment intensification in both cases in the absence of any renal BVAS items. | — |
Countries
Germany
Contacts
Public ContactAdrian Schreiber
Charité – Universitätsmedizin Berlin
Outcome results
None listed