Glomerulonephritis Acute
Conditions
Keywords
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Pauci-Immune Glomerulonephritis, urinary biomarker, Churg-Strauss Syndrome, Microscopic Polyangiitis, Granulomatosis with Polyangiitis, effector memory T lymphocytes, prediction
Brief summary
Urinary CD4+ and CD8+ T lymphocytes may predict renal flares in patients with inactive ANCA-associated vasculitis and thus serve as early non-invasive biomarkers. Urine samples of patients with inactive renal ANCA-vasculitis will be analysed by flow cytometry and compared to clinical outcome after 6 months.
Detailed description
Data of previous studies have shown that counts of urinary T lymphocyte subsets correlate with disease activity in several immunological renal diseases, e.g. ANCA-associated glomerulonephritis. Thus, study authors hypothesise that CD4+, respectively CD8+, T effector memory lymphocytes found in urine samples of patients with inactive ANCA-vasculitis predict subsequent renal flares. Therefore, quantification of these cellular subsets might reliably predict relapse of ANCA associated glomerulonephritis at an early stage. In a prospective experimental study urine of patients with ANCA-vasculitis and no renal involvement or patients in renal remission will be analysed by flow cytometry. After 6 months of observation, clinical outcome and potential renal relapse will be determined and correlated to initial T lymphocyte count.
Interventions
DIAGNOSTIC_TESTAnalysis of urine samples with flow cytometry
Urine samples will be conserved and frozen upon arrival. All samples will be stained according to T cell and TEC (tubular epithelial cells) panel with fluorochromes. T cell panel: CD3, CD4, CD8, CCR7, CD45RO, CD28, CD279; TEC panel: vimentin, cytokeratine, CD10, CD13, CD227, CD326
Sponsors
Charite University, Berlin, Germany
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* diagnosed ANCA-associated vasculitis (clinical diagnosis of granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis or microscopic polyangiitis consistent with the Chapel-Hill consensus definitions AND positive test for proteinase 3-ANCA or myeloperoxidase-ANCA) * no currently active renal involvement (defined as BVAS = 0 with exception of hematuria or proteinuria as signs of renal scars) * written and informed consent
Exclusion criteria
* urinary tract infection * active menstrual bleeding * active renal involvement * other active renal disease (e.g. diabetic nephropathy) Initially, we defined treatment with rituximab as
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prediction of renal relapse after six months depending initial CD4+ count | 6 months | * relapse defined as Birmingham Vasculitis Activity Score (BVAS) \> 1 + at least one renal element or * intensified treatment regime (Prednisolon equivalent \> 20 mg/d or novel induction treatment with Rituximab or Cyclophosphamide) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Prediction of renal relapse after six months depending initial CD8+ count | 6 months | — |
| Prediction of renal relapse after six months depending initial CD4+/CD8+ subsets | 6 months | Subsets: T effector memory cells (CD45RO+/CCR7-) |
| Prediction of renal relapse after 12 months depending initial CD4+ count | 12 months | — |
| Prediction of renal relapse after 12 months depending initial CD8+ count | 12 months | — |
| Prediction of renal relapse after 12 months depending initial CD4+/CD8+ subsets | 12 months | Subsets: T effector memory cells (CD45RO+/CCR7-) |
Countries
Germany
Outcome results
None listed