Systematic Transplantectomy Versus Conventional Care After Kidney Graft Failure

Study Overview
=================
Brief Summary
-----------------
Our hypothesis is early and systematic transplantectomy under a well-conducted immunosuppression is associated with a decreased risk of anti-HLA immunization against a conservative attitude including a gradual reduction of immunosuppression, with or without a transplantectomy performed for cause (clinical event). Observation or Investigation Method Used : The study is : multicenter prospective open randomized: patients are divided into two parallel groups: study group: transplantectomy within six weeks after return to dialysis, antiproliferatives stop at the start of dialysis, Maintenance anticalcineurin-based-immunosuppression without dose reduction up to two weeks after transplantectomy. Abrupt discontinuation of anticalcineurin two weeks after transplantectomy. Corticosteroids: 5mg per day until one month after transplantectomy then stop within one month. control group: No systematic transplantectomy. Antiproliferatives stop at the start of dialysis.Anticalcineurins half dose for 3 months, ¼ dose for 3 months and then stop. Corticosteroids:5 mg per day for 6 months, and then tapered and stop within 3 months. In the case of transplantectomy for cause in the control group, immunosuppression will be continued at the maintenance dose during the current surgical procedure, and withdrawn two weeks later,similary to systematic transplantectomy.

Official Title
-----------------
Interest of Systematic Transplantectomy Versus Conventional Care After Kidney Graft Failure

Conditions
-----------------
Renal Transplantation

Intervention / Treatment
-----------------
* Procedure: Systematic transplantectomy
* Procedure: Progressive reduction of immunosuppression


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥ 18 Years. Patients affiliated to health protection system, social security in France or any similar regimen. Renal transplant patient with end-stage transplantation, regardless of the number of previous transplants. Patient receiving immunosuppressive protocol based on anticalcineurin or mTOR inhibitors Patient should have resume hemodialysis within 4 weeks Duration of transplantation more than one year Patient with asymptomatic graft immunogenic potential residual >50% (calculated PIR during the re-dialysis) Patient not covered by any measure of legal protection. Exclusion Criteria: Immunogenic potential residual <50% Graft infection uncontrolled by treatment Active infectious pathology Inflammatory graft Uncontrolled arterial hypertention Inflammatory syndrome of undetermined origin with CRP>50mg/l Fever of unknown origin for more than 8 days T>38°C Contra-indication to surgery AVK treatment Patient candidate for a living donor within 12 months Monotherapy with calcineurin inhibitors or mTOR inhibitors Treatment directed against the humoral response in the 6 months preceding the recovery of dialysis (Rituximab IV-Ig or high doses) Presence of another transplant (pancreas, liver, heart, lung)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Study group<br>The study group corresponds to systematic transplantectomy under immunosuppressive therapy within two months after return to dialysis, | Procedure: Systematic transplantectomy<br>* Transplantectomy within two months after return to dialyse. Antiproliferatives stop at the start of dialysis. Maintenance basic immunosuppressive treatment without dose reduction up to two weeks after transplantectomy. Abrupt discontinuation of the basic immunosuppressive treatment ttwo weeks after transplantectomy. Maintenance corticosteroids at 5mg per day until one month after transplantectomy then stop corticosteroids within one month.<br>|
| Other: Control group<br>The control group corresponds to progressive reduction of immunosuppression without systematic transplantectomy after return to dialysis | Procedure: Progressive reduction of immunosuppression<br>* Progressive reduction of immunosuppression. Transplantectomy for cause only. Antiproliferatives withdrawn at the start of dialysis. Maintenance of anticalcineurin or mTOR inhibitors half dose for 3 months, ¼ dose for 3 months and then stop. Maintenance corticosteroids for 6 months up to 5 mg per day, and then soft stop in 3 months. In case of transplantectomy by reason in the control group, basic immunosuppression will be continued at the maintenance dose during the current surgical procedure, and withdrawn two weeks later, similary to the strategy used in the study group.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti HLA Immunization assessed by Luminex assay | Evaluate the interest of a transplantectomy early (<2 months after return to dialysis) and systematic under immunosuppressive in renal transplant patients after loss of renal graft function in terms of anti-HLA immunization (measured by Luminex test) a year after loss of renal graft function and return to dialysis in the renal transplant patient. Proportion of patients who developed HLA immunization (DSA)after systematic transplantectomy under immunosuppression versus progressive reduction of immunosuppression without transplantectomy | 12 months (M12) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kinetics anti-HLA antibodies after transplantectomy | Determine the kinetics of new onset anti-HLA antibodies at D0, D15, D30, M3, M6, M9 after systematic or for cause transplantectomy and in the year following graft failure and the proportion of immunized patients during the first 6 months after dialysis. HLA antibodies will be assessed by Luminex test. The specificity of antibodies against HLA I or HLA II will be determined, as well as Mean Immunofluorescence Intensity in each case. | 12 months after inclusion | 
| Morbidity and mortality after transplantectomy | Determine the morbidity and mortality after transplantectomy according to its indication, systematic or for cause (transplantectomy indications in the control group: persistent pain graft, unexplained fever, hematuria, inflammation or unexplained anemia ). | 12 months after inclusion | 
| Measuring the impact of systematic transplantectomy on mortality, inflammation, nutritional status, anemia, hypertension and cardiovascular risk factors | The following parameters will be measured at D0, M1, M3, M6, M9 and M12 after return to dialysis during the first year after kidney graft failure: CRP, pre-albuminemia, albuminemia, BMI, hemoglobin, hematocrit, blood pressure, cholesterol, LDL cholesterol and triglyceride. | 12 months | 
| Infectious comorbidity | The impact of early cessation of immunosuppression on infectious complications after kidney graft failure will assessed. For each patient, origin of infection, bacterial, viral, fungal, will determined. The total number of infection episodes during the first year will be analyzed in the two groups. | 12 months | 
| Costs of two strategies | To evaluate the medico-economic impact of each conservation strategy in the management of patients who return to dialysis | 12 months after inclusion | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Renal failure,, Transplantectomy, Immunosuppression, Sensitization