Chronic Transplant Glomerulopathy and Regulation of Expression of Ephrin B1

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Chronic Transplant Glomerulopathy and Regulation of Expression of Ephrin B1

Conditions
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Kidney Transplantation

Intervention / Treatment
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* Other: biological analysis


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic transplant glomerulopathy, antibody mediated rejection, Ephrin-B1