Clinical trial NCT02147210: Chronic Transplant Glomerulopathy and Regulation of Expression of Ephrin B1
Official title: Chronic Transplant Glomerulopathy and Regulation of Expression of Ephrin B1
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Kidney Transplantation
Keywords: Chronic transplant glomerulopathy
antibody mediated rejection
Ephrin-B1
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2014-05-26
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
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

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Expression level of ephrin-B1 in biopsies from kidney transplant
timeFrame: Day 1
Secondary outcomes:
measure: Level of expression of the gene encoding for ephrin-B1
timeFrame: Day 1
measure: Kinetics of expression of ephrin-B1
timeFrame: Day 1
Other outcomes:
Locations:
city: Toulouse
country: France
facility: Service d'Anatomie Pathologique et Histologie-Cytologie Hôpital Rangueil
Study officials:
affiliation: Service d'Anatomie Pathologique et Histologie-Cytologie,Rangueil Hospital, University Hospital of Toulouse
name: Céline Guilbeau-Frugier, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Pharmacology,Toulouse University Hospital and INSERM U1048
name: Jean-Michel Senard, Md PhD
role: STUDY_DIRECTOR
References: