The investigator hypothesizes that the combined use of (1) Donor-derived cell-free DNA (dd-cfDNA) in peripheral blood predicting anti-donor immunological activation or quiescence (2) interactive and actionable data analytics delivered at the bedside will promote safe clinical follow-up of kidney transplant patients with less need for invasive biopsy and less induced risk surveillance by allograft protocol biopsies to assess allograft rejection in clinically stable kidney transplant patients.
In addition, the evaluation of the transcriptional changes in tissue samples in selected patients using automated processing of digital slide images and intragraft gene expression profiles will provide a better diagnosis of the rejection mechanisms to provide the best therapeutic approach as compared to current clinical practice.
We therefore propose a French, multicenter, prospective randomized trial comparing two strategies of follow-up: in the first group, a biopsy is performed at M3, M12 and for clinical indication whenever considered necessary by the clinician during the first 18 months of follow-up after transplant. In the second group, patients will have the same follow-up as in the first group, but reports providing dd-cfDNA results and relevant medical parameters will be provided to the physician to help him in the decision to perform a biopsy or not.
All men and women, age ≥18 years old.
Subject must be a recipient of a non-combined renal transplant from a deceased or living donor. It can be a re transplantation after a graft loss of function or graft rejection
Subject is willing and able to provide signed written informed consent and willing to comply with study procedures
Women of Childbearing Potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study in such a manner that the risk of pregnancy is minimized.
Subjects who are legally detained in an official institution or under legal protection
Any condition that, in the opinion of the investigator, might interfere with the patient 's participation in the study, poses an added risk for the patient, or confounds the assessment of the patient
History of multi-organ transplant (interference with rejection natural history).
Parallel
dd-cfDNA-guided
Biological/VaccineIn groups I and II, the blood sample for dd-cfDNA assay will be taken on D0, just prior to transplantation, for all patients. in addition, for patients following a dd-cf DNA-guided strategy based on dd-cf DNA ; samples for dd-cf DNA assay will be taken at M3 and M12 visits and at visits for clinical indication (5 maximum) and the blood will be sent to the PARCC technical platform of INSERM UMR 970. By combining the dd-cfDNA level and relevant medical data, an integration report will be sent to the centers to stratify patients into high-risk or low-risk rejection profiles. If the patient is classified in the "low risk of rejection" subgroup, he may decide not to perform the biopsy. If the patient is classified in the "high risk of rejection" subgroup, he may decide to perform the biopsy within 15 days of the sample being taken. the decision to perform the biopsy is left to the discretion of the physician.
compare levels of eGFR measured by CKD-EPI equation in both arms
Comparison of the levels of eGFR (mL/min/1.73m2) in both arms estimated by glomerular filtration rate (CKD-EPI eGFR) at 18 months' post-transplantation
modification of the immunosuppression treatment
To assess the rate of modification of the immunosuppression treatment in both groups
graft survival rates
To assess predicted graft survival rates in both groups using the iBox
biopsy-proven rejections
compare the rate of biopsy-proven rejections in both groups
incidence of death
compare the incidence of death and allograft loss in both groups
rate of biopsies
Comparison of The mean eGFR in both Groups estimated by glomerular filtration rate (CKD-EPI eGFR) at 12 months' post-transplantation and of the number of allograft rejection.
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