Urinary T Lymphocytes Predict Renal Flares in Patients With Inactive ANCA-associated Glomerulonephritis

Study Overview
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Brief Summary
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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
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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.

Official Title
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Urinary T Lymphocytes Predict Renal Flares in Patients With Inactive Anti-neutrophil Cytoplasmic Antibody (ANCA) Associated Glomerulonephritis

Conditions
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Glomerulonephritis Acute

Intervention / Treatment
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* Diagnostic Test: Analysis of urine samples with flow cytometry


Participation Criteria
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Eligibility Criteria
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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 exclusion criteria. However, upon closer examination, we recognized that this exclusion criterion was overly restrictive and may have inadvertently excluded eligible participants who met our other inclusion criteria. As a result of this reassessment, we have revised our exclusion criteria to no longer exclude individuals solely on the basis of receiving rituximab treatment.

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 |
| --- | --- |
| No renal involvement<br>Patients with ANCA-vasculitis and no ANCA-associated renal involvement in disease history | Diagnostic Test: Analysis of urine samples with flow cytometry<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>|
| Renal remission<br>Patient with ANCA-vasculitis in renal remission | Diagnostic Test: Analysis of urine samples with flow cytometry<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 |
| --- | --- | --- |
| Prediction of renal relapse after six months depending initial CD4+ count | 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) | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Subsets: T effector memory cells (CD45RO+/CCR7-) | 6 months | 
| 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 | Subsets: T effector memory cells (CD45RO+/CCR7-) | 12 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 Glomerulonephritis, urinary biomarker, Churg-Strauss Syndrome, Microscopic Polyangiitis, Granulomatosis with Polyangiitis, effector memory T lymphocytes, prediction