Mass Spectrometry-based Proteomics in Microvascular Inflammation Diagnosis in Kidney Transplantation.

NCT04851145 | Completed

• 1 other identifier: CHUBX 2020/47
• Study Type: interventional
• Target: 141
• Locations: 1 country
• Sites: 3

Brief Summary

Microvascular inflammation, the hallmark histological criteria of antibody-mediated rejection in kidney transplantation, remains an issue in routine practice, due to a lack of reproducibility in its recognition by pathologists and an incomplete comprehension of its pathophysiology, leading to a poor treatment efficacy. The main objective of this study is to assess the performances of tissue proteic signatures designed for the diagnosis of microvascular inflammation in kidney transplantation, from formalin-fixed and paraffin-embedded (FFPE) allograft biopsies analyzed by mass spectrometry-based proteomics.

Conditions

Kidney Transplantation; Graft Rejection; Humoral Immunity; Proteomics

Keywords

Antibody-mediated rejection; microvascular inflammation; proteomics; kidney transplantation

Outcome Measures

Primary Outcomes (1)

• Assessing diagnostic performance of tissue protein signature

  The primary outcome is the sensitivity and specificity of tissue protein signature in the diagnosis of microvascular inflammation (MVI) in kidney transplantation, the diagnostic reference standard being based on the 2019 Banff classification (histological and biological criteria). This primary outcome is based on FFPE kidney allograft biopsies.

  18 months after inclusion

Secondary Outcomes (4)

• Assessing the diagnostic performance of urine protein signatures

  18 months after inclusion

• Assessing the performance of tissue proteomic signature

  18 months after inclusion

• Assessing the performance of urine proteomic signature

  18 months after inclusion

• Compare protein profiles observed within different phenotypes of MVI in kidney transplantation

  18 months after inclusion

Study Arms (1)

Experimental

EXPERIMENTAL

Diagnostic Test: Mass spectrometry-based proteomics of FFPE biopsies and urine samples

Interventions

Mass spectrometry-based proteomics of FFPE biopsies and urine samples DIAGNOSTIC_TEST

The biopsy and urine samples will be processed by the OncoProt platform (University of Bordeaux) for proteomic analysis by tandem mass spectrometry (label-free quantification) as follows: * Biopsies: laser microdissection of the renal cortex, fixation reversion, protein extraction and electrophoretic migration, tryptic digestion. * Urines: samples concentration by centrifugation/filtration and tryptic digestion according to a protocol adapted from the FASP method (Filter-Aided Sample Preparation)

Experimental

Eligibility Criteria

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

You may qualify if:

• Kidney transplant recipients
• Diagnosis based on the 2019 Banff classification (polyomavirus nephropathy, T cell-mediated rejection, borderline changes)
• The microvascular inflammation group with anti-HLA DSA is defined as follows:
• At least moderate microvascular inflammation: g + ptc \> 2
• At least one anti-HLA DSA in the serum at the time of biopsy, with a Mean Fluorescence Intensity (MFI) \> 3000 for the immunodominant DSA or the sum of the DSA
• The microvascular inflammation group without anti-HLA DSA is defined as follows:
• At least moderate microvascular inflammation: g + ptc \> 2
• No historical anti-HLA DSA or at the time of biopsy, MFI \< 500
• The stable graft recipients group is defined as follows:
• Glomerual Filtration Rate \> 40ml/min, without clinical proteinuria
• No detectable DSA
• Protocol biopsy at 1 year posttransplantation without specific lesion or nonspecific severe lesion
• The chronic nonspecific graft changes group is defined as follows:
• Moderate to severe interstitial fibrosis and tubular atrophy, in the absence of specific lesions: active rejection (antibody-mediated or T cell-mediated), borderline lesions, recurrent or de novo nephropathy, polyomavirus associated nephropathy.
• No C4d deposits on peritubular capillaries

You may not qualify if:

• Minor patients
• Mixed rejection (antibody-mediated and T cell-mediated)
• Recurrent or de novo nephropathy
• Specific treatment of rejection (T cell-mediated or antibody-mediated) in the last 6 months, excluding induction and
• Baseline immunosuppressive treatment.

Sponsors & Collaborators

• University Hospital, Bordeaux: lead

Study Sites (3)

Hôpital Pellegrin

Bordeaux, 33000, France

Location

Hôpital Edouard Herriot

Lyon, 69003, France

Location

Hôpital Necker

Paris, 75015, France

Location

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2021
• First Posted: April 20, 2021
• Study Start: November 8, 2021
• Primary Completion: May 5, 2024
• Study Completion: May 5, 2024
• Last Updated: December 24, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3)