Urinary T Cell Biomarker for Prediction in ANCA Glomerulonephritis

Study Overview
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Brief Summary
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Urinary T lymphocytes may be predictive for clinical outcome in patients with ANCA associated glomerulonephritis (ANCA GN). The investigators hypothesize that the amount of CD4+ effector/memory T cells in urine at time of diagnosis predicts the outcome of patients with active ANCA GN after 6 months of therapy. In a prospective, six-months follow-up study patients' urine will be analysed by flow cytometry every 60 days (+/- 10d). Treatment will be performed to the discretion of the treating clinician. After 6 months of treatment response will be determined as either complete response or partial response.

Official Title
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Phenotype of Urinary CD4+ T Cells as Biomarkers for Prediction of Outcome in ANCA Glomerulonephritis

Conditions
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Glomerulonephritis Acute

Intervention / Treatment
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* Diagnostic Test: Flow cytometry analysis of urine samples


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent Biopsy proven ANCA related glomerulonephritis In absence of biopsy clinical diagnosis of ANCA related glomerulonephritis Exclusion Criteria: Biopsy proven non-ANCA related kidney disease Active menstrual bleeding Urinary tract infection Kidney transplantation during observational period

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active ANCA glomerulonephritis<br>Patients with ANCA related disease (Microscopic Polyangiitis, Granulomatosis with Polyangiitis or Churg-Strauss Syndrome) and active renal involvement | Diagnostic Test: Flow cytometry analysis of urine samples<br>* 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<br>|
| Control<br>Patients with ANCA related disease (MPA, GPA, CSS) without renal involvement or complete remission | Diagnostic Test: Flow cytometry analysis of urine samples<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phenotype of CD4+ T cells at time point 0 predictive of clinical outcome in patients with active ANCA-assosciated glomerulonephritis | Urinary CD4+ effector/memory T cell counts at time point 0 (time of diagnosis) predict clinical outcome (complete or partial response) after 6 months of treatment in patients with active ANCA-assosciated glomerulonephritis. The frequency of effector/memory CD4+ T lymphocytes is higher in patients with non- or partial response. Complete response at 24 weeks: BVAS = 0 Partial response at 24 weeks: at least one renal element of the BVAS score. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Analysis of patients with persistent renal abnormalities as partial response |  | 6 months | 
| Phenotype of CD8+ T cells at time point 0 predictive of clinical outcome in patients with active ANCA-assosciated glomerulonephritis | Urinary CD8+ effector/memory T cell counts at time point 0 (time of diagnosis) predict clinical outcome (complete or partial response) after 6 months of treatment in patients with active ANCA-assosciated glomerulonephritis. The frequency of effector/memory CD8+ T lymphocytes is higher in patients with non- or partial response. | 6 months | 
| Subgroup analysis according to treatment |  | 6 months | 
| Diagnosis of active glomerulonephritis in Patients with ANCA associated vasculitis | Diagnosis according to initial T cell count | 6 months | 
| Prediction of complete or partial response according to normalization of the amount of urinary T cells at time point 2 and 4 |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Pauci-Immune Vasculitis, Churg-Strauss Syndrome, Granulomatosis with Polyangiitis, Microscopic Polyangiitis, urinary biomarker, outcome, prediction,, urinary effector memory T lymphocytes, glomerulonephritis, non-invasive biomarker, flow cytometry, treatment outcome, CD4-Positive T-Lymphocytes/immunology