Renal Graft Function After Treatment With Erythropoietin (EPO)

Study Overview
=================
Brief Summary
-----------------
Background : Numerous studies have outlined the cellular pleiotropic effects of erythropoietin (EPO) and their role in the prevention of ischemic-reperfusion lesion such as after acute ischemic injury of the brain or the heart. However, most of these studies were carried out in animal models and no definitive proof exists today to demonstrate that EPO has similar beneficial effects in human pathology. Purpose : The aim of the study is to demonstrate that in humans, EPO can protect against ischemic-reperfusion lesions in a model of ischemia i.e. kidney transplantation.

Detailed Description
-----------------
Abstract : Since the discovery that EPO and its receptor are expressed in various tissues, numerous studies have demonstrated that EPO is not only involved in erythropoiesis but also exerts pleiotropic effects on cells. Among these, one of the most exciting is its role in the prevention of ischemic-reperfusion lesions such as after acute ischemic injury of the brain or the heart. However, most of these studies were carried out in animal models and no definitive proof exists today to demonstrate that EPO has similar beneficial effects in human pathology. Kidney transplantation is one ischemic situation where EPO pleiotropic effects could be of great interest since ischemic-reperfusion lesions have been involved in delayed graft function and impaired graft outcomes. The aim of this prospective randomized double blind study is to assess the effect of 100 000 UI of béta-epoiétin on kidney graft function, given to the deceased donor one hour before the retreaval of the organ. Recipients will be followed for three months in order to evaluate kidney function (glomerular filtration rate) and the number of acute rejection episodes to determine whether beta-epoietin could modify the immunogenicity of the graft.

Official Title
-----------------
Interest of a High Dose of Erythropoietin Administered During Graft Processing for Early Graft Outcome in Kidney Transplant Recipients.

Conditions
-----------------
Ischemia

Intervention / Treatment
-----------------
* Drug: beta-epoietin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: donor: cadaveric organ donor, age ≥ 18 years, mono-organ (kidney) retrieval, retrieval done in the centres of Limoges, Bordeaux, Toulouse, Angers, Brest, Nantes, Poitiers, Rennes, Tours, hematocrit ≤ 45%. Recipient: age ≥ 18 years, on the waiting list for a kidney graft. Exclusion Criteria: living donors, age under 18 years, multi-organ retrieval, donor hematocrit above 45%

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

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Graft with EPO<br>intravenous 1000 000UI beta-epoietin one hour before organe retrieval. | Drug: beta-epoietin<br>* 100 000UI beta-epoietin injection one hour before organ retrieval<br>|
| No Intervention: graft without EPO<br>no injection befoe organ retrieval | |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| a plasma creatinin level | To assess the effect of an injection of 100 000 UI of beta-epoitein during graft processing, on the proportion of renal recipients with a plasma creatinin level below 250 µM at day 5 after transplantation in the absence of hemodialysis, death or transplantectomy. | 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of delayed graft function defined as follows: | The incidence of delayed graft function defined as follows: combination of the need for dialysis (except dialysis for hyperkalemia or volume overload) or creatinine reduction ratio of less than 25% within the first 48 h post-transplant. | 48 hours | 
| MDRD glomerular filtration rate at one and three months | MDRD glomerular filtration rate at one and three months | three months | 
| The incidence of acute rejection during the first three months | The incidence of acute rejection during the first three months | three months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cadaveric organ donor, high dose of EPO, transplant kidney, mono-organ (kidney) retrieval, patient, kidney graft