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

NCT04428398 | Completed

• 1 other identifier: PRE-FLARED
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 2

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.

Conditions

Glomerulonephritis Acute

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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

• 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

Study Arms (2)

No renal involvement

Patients with ANCA-vasculitis and no ANCA-associated renal involvement in disease history

Diagnostic Test: Analysis of urine samples with flow cytometry

Renal remission

Patient with ANCA-vasculitis in renal remission

Diagnostic Test: Analysis of urine samples with flow cytometry

Interventions

Analysis of urine samples with flow cytometry DIAGNOSTIC_TEST

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

No renal involvement; Renal remission

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients in medical wards or at outpatient departments of 2 facilities: * Charité - Universitätsmedizin Berlin * Helios Klinikum Berlin-Buch

You may qualify if:

• 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

You may not qualify if:

• urinary tract infection
• active menstrual bleeding
• active renal involvement
• other active renal disease (e.g. diabetic nephropathy)

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead

Study Sites (2)

Charité - Universitätsmedizin Berlin

Berlin, 10117, Germany

Location

Helios Klinikum Berlin-Buch

Berlin, 13125, Germany

Location

Related Publications (6)

• Goceroglu A, Berden AE, Fiocco M, Flossmann O, Westman KW, Ferrario F, Gaskin G, Pusey CD, Hagen EC, Noel LH, Rasmussen N, Waldherr R, Walsh M, Bruijn JA, Jayne DR, Bajema IM; European Vasculitis Society (EUVAS). ANCA-Associated Glomerulonephritis: Risk Factors for Renal Relapse. PLoS One. 2016 Dec 14;11(12):e0165402. doi: 10.1371/journal.pone.0165402. eCollection 2016.

  PMID: 27973575 BACKGROUND

• Menez S, Hruskova Z, Scott J, Cormican S, Chen M, Salama AD, Alasfar S, Little MA, Safrankova H, Honsova E, Tesar V, Geetha D. Predictors of Renal Outcomes in Sclerotic Class Anti-Neutrophil Cytoplasmic Antibody Glomerulonephritis. Am J Nephrol. 2018;48(6):465-471. doi: 10.1159/000494840. Epub 2018 Nov 23.

  PMID: 30472700 BACKGROUND

• Cordova-Sanchez BM, Mejia-Vilet JM, Morales-Buenrostro LE, Loyola-Rodriguez G, Uribe-Uribe NO, Correa-Rotter R. Clinical presentation and outcome prediction of clinical, serological, and histopathological classification schemes in ANCA-associated vasculitis with renal involvement. Clin Rheumatol. 2016 Jul;35(7):1805-16. doi: 10.1007/s10067-016-3195-z. Epub 2016 Feb 6.

  PMID: 26852317 BACKGROUND

• Enghard P, Rieder C, Kopetschke K, Klocke JR, Undeutsch R, Biesen R, Dragun D, Gollasch M, Schneider U, Aupperle K, Humrich JY, Hiepe F, Backhaus M, Radbruch AH, Burmester GR, Riemekasten G. Urinary CD4 T cells identify SLE patients with proliferative lupus nephritis and can be used to monitor treatment response. Ann Rheum Dis. 2014 Jan;73(1):277-83. doi: 10.1136/annrheumdis-2012-202784. Epub 2013 Mar 8.

  PMID: 23475982 BACKGROUND

• Abdulahad WH, Kallenberg CG, Limburg PC, Stegeman CA. Urinary CD4+ effector memory T cells reflect renal disease activity in antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2009 Sep;60(9):2830-8. doi: 10.1002/art.24747.

  PMID: 19714581 BACKGROUND

• Prskalo L, Skopnik CM, Goerlich N, Freund P, Wagner L, Grothgar E, Mirkheshti P, Klocke J, Sonnemann J, Metzke D, Schneider U, Hiepe F, Eckardt KU, Salama AD, Bieringer M, Schreiber A, Enghard P. Urinary CD4 + T Cells Predict Renal Relapse in ANCA-Associated Vasculitis. J Am Soc Nephrol. 2024 Apr 1;35(4):483-494. doi: 10.1681/ASN.0000000000000311. Epub 2024 Jan 17.

  PMID: 38231590 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

urine samples (approximately 60 mL per patient)

MeSH Terms

Conditions

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Churg-Strauss Syndrome; Microscopic Polyangiitis; Granulomatosis with Polyangiitis

Interventions

Flow Cytometry

Condition Hierarchy (Ancestors)

Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Granuloma; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Philipp Enghard

  Charite University, Berlin, Germany

  PRINCIPAL INVESTIGATOR

• Adrian Schreiber, PD Dr. med.

  Charite University, Berlin, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PD Dr. med.

Study Record Dates

• First Submitted: June 9, 2020
• First Posted: June 11, 2020
• Study Start: May 1, 2020
• Primary Completion: September 1, 2021
• Study Completion: September 1, 2021
• Last Updated: November 14, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share

Locations

DE (2)