Chronic Transplant Glomerulopathy and Regulation of Expression of Ephrin B1 (GARRE)

The principal purpose is the study of the regulation of the expression of ephrin-B1 by immunofluorescence in kidney biopsies of patients with Chronic transplant glomerulopathy (CTG) compared to biopsies prior to the CTG, in same patients. Level of fluorescence in CTG biopsy will be the experimental reference value.

Study Overview

• Status: Completed
• Conditions: Kidney Transplantation
• Intervention / Treatment: Other: biological analysis

Detailed Description

Chronic transplant glomerulopathy (CTG) is a specific lesion of kidney transplantation and a poor prognostic factor affecting transplant survival. Diagnosis remains only microscopic and lesions are irreversible. Recent studies prove that there is a strong correlation between CTG and antibody mediated rejection (AMR) with a possible link with chronic aggression of the endothelial cell. However, for unknown reason, all AMR does not lead to a CTG. Our recent data on mice demonstrated that ephrin-B1 is expressed in the glomerular endothelial cells and knockout mice for the gene encoding ephrin-B1 develop progressively ultrastructural glomerular lesions close to modifications observed in CTG, as well as proteinuria and chronic renal failure, suggesting that ephrin B1 could participate to CTG. Moreover, in a preliminary study on human kidney transplant biopsy we observed decrease in ephrin-B1 immunofluorescence on glomerulus when CTG, even in low grade. These data, and ultrastructural modifications in Knock Out (KO) mice suggest that early regulation of kidney expression of ephrin-B1 in the glomerulus may occur during the process leading to the CTG as antibody-mediated kidney rejection (AMR).

The purpose of the study is to determinate if ephrin-B1 expression is modified in CTG.

• Study Type: Observational
• Enrollment (Anticipated): 60

Contacts and Locations

Study Locations

• France
  • Toulouse, France, 31059
    • Service d'Anatomie Pathologique et Histologie-Cytologie Hôpital Rangueil

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Biopsies from patients corresponding to eligibility criteria (see below) will be selected from the list of kidney transplant patients followed up in the Toulouse University Hospital. They will be divided into two groups matched for age, sex and time of kidney transplantation (n = 30 for each group). Iterative biopsies are conserved in the collection of tissue samples of the CHU

Description

Inclusion Criteria:

• Kidney transplant patient for whom renal biopsies are stored in the "collection of the University Hospital Toulouse" (collection N° DC-2009-989) and who received information on the purpose of the study, use of biopsies and who has not manifested any opposition.
• Kidney transplant patient with iterative biopsies with at least: post-surgery biopsy D0 (or early post-transplant biopsy D7 and at least one biopsy protocol. - Age> 18 years Case group: - Kidney transplant patient, followed up by "organ transplant unity" of CHU Toulouse, with antecedent of CMR progressing to CTG between 2006 and 2013. Control group: - Kidney transplant patient, followed up by "organ transplant unity" of CHU Toulouse, with antecedent of CMR without progressing to CTG between 2006 and 2013

Exclusion Criteria:

• patient with uncontrolled hypertension - patient with diabetes mellitus -
• patient treated or who was treated with mTOR inhibitor - recurrence of the initial glomerular pathology - de novo glomerulopathy - patient including in another study with an exclusion period still going

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
1-Case; patients who developed CTG secondary to antibody-mediated kidney rejection (AMR), diagnosed by microscopic analysis.	Other: biological analysis
2-Control; patients with antibody-mediated kidney rejection (AMR) but without CTG	Other: biological analysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expression level of ephrin-B1 in biopsies from kidney transplant	Analysis on all biopsies available from transplantation to Chronic transplant glomerulopathy by immunofluorescence (by anti-C4d)	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Level of expression of the gene encoding for ephrin-B1	Analysis on all biopsies available from transplantation to Chronic transplant glomerulopathy by quantitative PCR (qPCR) and normalized to the expression of the gene encoding for GAPDH	Day 1
Kinetics of expression of ephrin-B1	Analysis on all biopsies available from transplantation to CTG by quantitative PCR (qPCR) and normalized to the expression of the gene encoding for GAPDH	Day 1

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Investigators: Principal Investigator: Céline Guilbeau-Frugier, MD, Service d'Anatomie Pathologique et Histologie-Cytologie,Rangueil Hospital, University Hospital of Toulouse; Study Director: Jean-Michel Senard, Md PhD, Department of Pharmacology,Toulouse University Hospital and INSERM U1048

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: May 19, 2014
• First Submitted That Met QC Criteria: May 23, 2014
• First Posted (Estimate): May 26, 2014

Study Record Updates

• Last Update Posted (Actual): March 7, 2017
• Last Update Submitted That Met QC Criteria: March 5, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: antibody mediated rejection; Chronic transplant glomerulopathy; Ephrin-B1
• Other Study ID Numbers: 13 194 02; AOL 2013 (Other Grant/Funding Number: University Hospital Toulouse)