Evaluation of the Level of Expression of CD45RC on T Lymphocytes as a Predictive Biomarker of Acute Rejection After Renal Transplantation (ECLAT)

Chronic renal failure is a major public health problem in industrialized countries, due to its frequency - about 3 million patients in France - and its socio-economic impact. At the end stage of renal failure, renal transplantation is the best treatment, allowing an improvement in patient survival compared to treatment by extra-renal purification. Despite improved immunosuppressive strategies, allograft rejection is common in transplantation - between 15% and 25% in the first year - and is associated with lower renal graft survival.

Different risk factors for rejection have been well identified, such as the young age of the recipient or a high number of human leukocyte antigen (HLA) incompatibilities between the donor and the recipient. However, these risk factors do not accurately identify the risk of acute rejection in order to optimize and individualize immunosuppressive strategies.

Also, the search for biomarkers to predict allograft tolerance prior to transplant is a major goal in renal transplantation.

The onset of acute rejection is caused by the ability of the recipient's T cells to recognize alloantigens. The CD45 molecule is a highly expressed tyrosine phosphatase on the surface of the lymphocytes that plays an important role in the activation of the T cell.

Investigators showed that the level of expression of CD45RC on T lymphocytes was associated with the risk of acute rejection. Thus, from a retrospective cohort of 89 renal transplant patients followed, recipients with a high percentage of circulating CD8 lymphocytes expressing high CD45RC (CD45RChigh) before transplant had a 5 to 8-fold higher risk of developing acute rejection of allograft during follow-up (11-year average follow-up) compared to recipients with a low percentage of CD8+CD45RChigh.

The purpose of this study is to confirm the first retrospective results on a larger prospective and contemporary regional cohort.

Study Overview

• Status: Recruiting
• Conditions: End-stage Renal Disease
• Intervention / Treatment: Other: Blood samples

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anne-Sophie GARNIER, MD; Phone Number: +33 0241356075; Email: AnneSophie.Garnier@chu-angers.fr
• Study Contact Backup: Name: Béatrice GABLE; Email: begable@chu-angers.fr

Study Locations

• France
  • Angers, France
    • Recruiting
    • Dr Anne-Sophie GARNIER
    • Contact: Anne-Sophie GARNIER, Dr; Phone Number: +33 2 41 35 44 76; Email: annesophie.garnier@chu-angers.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients over 18 and under 70 years old
• Patients in care for a first priority renal transplant.
• Patients with low immunological risk
• Patients with prior written informed consent

Exclusion Criteria:

• Poor understanding of the French language
• Pregnant, breastfeeding or partying women
• Persons deprived of liberty by an administrative or judicial decision
• Persons undergoing psychiatric care under duress
• Adults who are subject to a legal or non-state protection measure to express their consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Patient in need of a kidney transplant	Other: Blood samples; Blood samples the day of the surgery and 4 times during the next year. Blood samples and histological slides taken at each biopsy and if there is suspicion of rejection of the graft

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of patient with acute rejection diagnosis confirmed by anatomopathological analysis of a graft biopsy	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of CD45RC for patient with acute rejection suspicion	acute rejection confirmed or not	12 months
Rate of CD45RC on circulating T lymphocytes	Evolution of the expression of CD45RC in the first year after introduction of immunosuppressive therapy	from date of randomization until the date of acute rejection, up to 12 months
Rate of CD45RC on circulating T lymphocytes the day of acute rejection	day of acute rejection	12 months
Rate of CD4, CD8, CD45RA, CD25, CD127, CD19 markers on T cells the day of acute rejection	day of acute rejection	12 months
anti-HLA antibodies' dosage at the time of acute rejection		12 months
cytokines' dosage	describe cytokine profile	Day 1

Collaborators and Investigators

• Sponsor: University Hospital, Angers

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2021
• Primary Completion (Estimated): February 2, 2025
• Study Completion (Estimated): February 2, 2026

Study Registration Dates

• First Submitted: June 11, 2019
• First Submitted That Met QC Criteria: June 19, 2019
• First Posted (Actual): June 21, 2019

Study Record Updates

• Last Update Posted (Actual): June 11, 2024
• Last Update Submitted That Met QC Criteria: June 10, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Renal Insufficiency, Chronic; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Failure, Chronic
• Other Study ID Numbers: 49RC18_0018

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No