Clinical trial NCT04428398: Urinary T Lymphocytes Predict Renal Flares in Patients With Inactive ANCA-associated Glomerulonephritis
Official title: Urinary T Lymphocytes Predict Renal Flares in Patients With Inactive Anti-neutrophil Cytoplasmic Antibody (ANCA) Associated Glomerulonephritis
Study type: OBSERVATIONAL
Overall status: COMPLETED
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
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
First posted: 2020-06-11
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients in medical wards or at outpatient departments of 2 facilities:

* Charité - Universitätsmedizin Berlin
* Helios Klinikum Berlin-Buch

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Prediction of renal relapse after six months depending initial CD4+ count
timeFrame: 6 months
Secondary outcomes:
measure: Prediction of renal relapse after six months depending initial CD8+ count
timeFrame: 6 months
measure: Prediction of renal relapse after six months depending initial CD4+/CD8+ subsets
timeFrame: 6 months
measure: Prediction of renal relapse after 12 months depending initial CD4+ count
timeFrame: 12 months
measure: Prediction of renal relapse after 12 months depending initial CD8+ count
timeFrame: 12 months
measure: Prediction of renal relapse after 12 months depending initial CD4+/CD8+ subsets
timeFrame: 12 months
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Berlin
country: Germany
facility: Helios Klinikum Berlin-Buch
Study officials:
affiliation: Charite University, Berlin, Germany
name: Philipp Enghard
role: PRINCIPAL_INVESTIGATOR
affiliation: Charite University, Berlin, Germany
name: Adrian Schreiber, PD Dr. med.
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
citation: 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.