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

Glomerulonephritis Acute Clinical Trial

— PRE-FLARED  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04428398
• Other study ID #: PRE-FLARED
• Status: Completed
• Start date: May 1, 2020
• Est. completion date: September 1, 2021

Study information

• Verified date: November 2023
• Source: Charite University, Berlin, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: September 1, 2021
• Est. primary completion date: September 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Glomerulonephritis
• Glomerulonephritis Acute

Intervention

Diagnostic Test:
• Analysis 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

Locations

Country	Name	City	State
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	Helios Klinikum Berlin-Buch	Berlin

Sponsors (1)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany

Country where clinical trial is conducted

Germany, 

References & Publications (5)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Prediction of renal relapse after six months depending initial CD8+ count		6 months
Secondary	Prediction of renal relapse after six months depending initial CD4+/CD8+ subsets	Subsets: T effector memory cells (CD45RO+/CCR7-)	6 months
Secondary	Prediction of renal relapse after 12 months depending initial CD4+ count		12 months
Secondary	Prediction of renal relapse after 12 months depending initial CD8+ count		12 months
Secondary	Prediction of renal relapse after 12 months depending initial CD4+/CD8+ subsets	Subsets: T effector memory cells (CD45RO+/CCR7-)	12 months