Endothelial Microparticules and Antibody Mediated Rejection and Kidney Transplantation: Biomarker of Antibody-mediated Rejection in Kidney Transplantation

NCT03098238 | Completed DMC

• 2 other identifiers: RECHMPL16_0263UF 9746
• Study Type: interventional
• Target: 249
• Locations: 1 country
• Sites: 1

Brief Summary

Context and rationale: Antibody-mediated rejection is the leading cause of long-term renal graft loss. It's due to the production by the recipient of antibodies directed against antigens (belonging or not to the HLA system) present on the surface of the donor specific endothelial cells (DSA), leading to graft failure. The main difficulty to manage the humoral rejection is the delay of the diagnosis and the treatment to slow the evolution towards fibrosis. Positivity of anti-HLA antibodies is the main risk factor for the rejection but the only way to make the diagnosis of humoral rejection is to perform a graft biopsy, an invasive process. Endothelial microparticles (MPE) are small membrane vesicles generated by endothelial cell activation and / or apoptosis processes. We test the hypothesis that endothelial microparticles are an early diagnostic biomarker of humoral rejection in renal transplantation allowing to detect it at the "subclinical" stage. Primary and secondary objectives: The main objective of this study is to estimate the performance of MPE plasma concentration for the diagnosis of humoral rejection in renal transplant patients with DSA. The secondary objective is to investigate by mass spectrometry the MPEs specific to the endothelium of the graft and to evaluate their diagnostic performance in relation to non-specific MEPs Methodology : We will conduct a cross-sectional evaluation of a diagnostic method from a collection of biological samples. The gold standard for the diagnosis of humoral rejection is the histological diagnosis on graft biopsy. The new test under study will be the flow cytometric assay of the MPE concentration carried out on plasma taken on the day of the graft biopsy. Feasibility: Among the active list of renal transplant patients attending the Montpellier University Hospital, we estimate that we can include the number of subjects required (N = 250) over 18 months. This work will be carried out in a laboratory with all the tools and techniques used, in particular flow cytometry and mass spectrometry, perfectly mastered and realized on dedicated technical platforms Benefits / Outlook: find a non-invasive early diagnostic biomarker to detect humoral rejection from the "subclinical" stage in order to set up an adapted treatment as quickly as possible.

Conditions

Renal Transplantation

Outcome Measures

Primary Outcomes (1)

• Plasma concentration of endothelial microparticles

  Endothelial microparticle (MPE) plasma concentration for the diagnosis of humoral rejection in renal transplant patients with DSA.

  1 day

Secondary Outcomes (1)

• Presence of specific MEPs

  1 day

Study Arms (3)

Patients without humoral rejection or DSA

OTHER

Renal transplant patients with systematic kidney biopsy at 3 months and 12 months Patients without humoral rejection or DSA (Donor Specific Antibodies)

Biological: Biological sample

Patient without humoral rejection with a DSA

OTHER

Patient without humoral rejection with a DSA (Donor Specific Antibodies)Patients with a graft biopsy for a donor-specific anti-HLA antibody

Biological: Biological sample

Patients with humoral rejection

OTHER

Patients with humoral rejection

Biological: Biological sample

Interventions

Biological sample BIOLOGICAL

Biological sampling of two citrate tubes (18 ml) during a normal blood

Patient without humoral rejection with a DSA; Patients with humoral rejection; Patients without humoral rejection or DSA

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Renal transplant patients monitored at Montpellier University Hospital
• With a recent or planned realization of a graft biopsy
• Patients with DSA (s) detected by Single Antigen Bead Assay (SAB, LabScreen Single Antigen, One Lambda Kit) with an average fluorescence intensity\> 500 IU Or Patients without DSA transplanted to a year with a systematic biopsy aspiration.

You may not qualify if:

• Refusal to participate in or to undergo the examination
• Major protected by guardianship
• History of treated humoral rejection
• Incompatible graft ABO
• Multi-organ transplantation
• Cardiovascular disease active (myocardial infarction \<3 months, arteriopathy obliterating lower limbs stage III or IV)
• Sepsis in progress
• Evolving Cancers
• Lupus nephropathy

Sponsors & Collaborators

• University Hospital, Montpellier: lead

Study Sites (1)

Uhmontpellier

Montpellier, 34295, France

Location

Study Officials

• Moglie LE QUINTREC DONNETTE

  University Hospital, Montpellier

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2017
• First Posted: March 31, 2017
• Study Start: November 30, 2017
• Primary Completion: June 4, 2020
• Study Completion: June 4, 2020
• Last Updated: December 14, 2022

Record last verified: 2020-01

Locations

FR (1)