Calcineurin inhibitors (CNI) remain the standard treatment in renal transplantation to prevent rejection. Currently the main limitation of kidney transplantation is the occurrence of chronic graft dysfunction due to the CNI nephrotoxicity. Thus, strategies to minimize or stop CNI have been developed as belatacept, a fusion protein (CTLA4-Ig) blocking the ligand of the main CD28 costimulatory molecule. In the original phase III trial, used de novo in combination with MMF (without CNI) belatacept allowed to obtain a better renal function as soon as 1 year and a better graft and patient survival after 7 years. Despite these excellent results, belatacept has not become the gold standard due to a higher incidence of early rejection. In addition, belatacept is not covered by the french social security policy, because benefits are considered insufficient with respect to the cost. Patients with poor early graft function are a preferred indication of belatacept. It is then used instead of CNI at 3 months post-transplant allowing to improve kidney function without over-risk of rejection. Currently after conversion, belatacept is maintained indefinitely due to the supposed CNI chronic nephrotoxicity. However this one is more and more questionable. Thus, the investigators assume that in patients with poor function at 3 months posttransplantation the belatacept's benefit could be obtained by a transient replacement of CNI by belatacept from 3 to 12 months post-transplantation. It is the feasibility of this strategy and its medico-economic impact that the investigators wish to study.
adult older than 18 years old.
transplantation of a deceased or living donor kidney (non-human leukocyte antigen(HLA)-identical) with blood type (ABO) compatibility
no contraindication to the protocol graft biopsy (10 weeks post transplant)
treatment by CNI / MPA +/- prednisone
Presence of Donor Specific Antibody during kidney transplant or appeared at 3 months post-transplantation.
seropositivity for HIV
another history of other solid organ transplants (outside the kidney)
primary non-function (persistence of a need for dialysis at 3 months post-transplantation)
Single group
Belatacept 250 Milligram Intravenous Powder for Solution
DrugPhase 1 (from 3 to 12 months post transplantation): conversion to belatacept (IV, 5mg/Kg days 1, 15,30, 45, 60 then every months) and CNI withdrawal. Phase 2 (from 12 to 18 months post transplantation) : belatacept arrest and CNI resumption (tacrolimus target 6 ng/ml)
Feasibility of a transient replacement of CNIs by belatacept in renal transplant patients with early graft dysfunction. Creatinine clearance did not decrease by more than 25% from the cessation of belatacept 6 months after reintroduction of CNI.
Feasibility was defined by preserved renal function and good tolerance 6 months after reintroduction of CNI. Renal function was defined as preserved if creatinine clearance (according to Chronic Kidney Disease - Epidemiology Collaboration (CKD-EPI)) did not decrease by more than 25% from the cessation of belatacept. The good tolerance of CNI was defined by the absence of complications leading to the cessation of treatment.
Evaluate the effectiveness of belatacept treatment on renal function (creatinine clairance) and to prevent rejection. (Number of rejection épisodes)
Longitudinal monitoring of renal function (Day 0, Month 3, Month 6, Month 9) and collection of rejection episodes.
Evaluate the tolerance of treatments (belatacept during phase 1 and CNI during phase 2). Number of adverse events.
Collection of infectious episodes and neoplasias
Estimate the cost of care (from 3 months to 18 months post-transplant) and compare with the cost of a theoretical arm benefiting from belatacept continuously and a theoretical arm benefiting from CNIs continuously.
Number of care resources used for treatment : number of medication, number of hospitalization, number of transportation, number of consultations, number of medical procedures, possible home help and associated costs over 15 months of follow-up, and collection of cost data in the literature for the comparison.
Evaluate the evolution of the quality of life during the 15 months of follow-up and compare it to a theoretical arm benefiting from belatacept continuously, and a theoretical arm benefiting from CNIs continuously: generic EuroQol-5D scale
Measurement of quality of life scores (generic EuroQol-5D scale) every 3 months for 15 months and collection of quality of life data in the literature for comparison.
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