Immunoregulatory Effects of Immunoglobulin Induction Therapy in Renal Transplant Recipients

Study Overview
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Brief Summary
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The aim of this randomized prospective study in renal transplant recipients is to investigate immunological short and long-term effects of an IVIG induction therapy. Furthermore clinical endpoints (patient and graft survival, incidence of acute and chronic rejection, infectious diseases and graft function) up to three years posttransplant will be analyzed.

Detailed Description
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Intravenous immunoglobulin (IVIG) preparations are known to be effective in the treatment of various autoimmune and inflammatory disorders due to their immunomodulatory and antiinflammatory properties. It has been demonstrated that IVIG is effective in the treatment of acute vascular rejection and steroid resistant cellular rejection. Furthermore, IVIG has been used to inhibit production of lymphocytotoxic antibodies in highly sensitized patients so that successful cadaveric or living renal transplantation could be performed. The aim of this randomized prospective study in renal transplant recipients is to investigate immunological short and long-term effects of an IVIG induction therapy on Th1, Th2 and B-cell/monocyte responses, expression of adhesion molecules, costimulatory factors and cytokine receptors and on secretion of immunoregulatory autoantibodies (anti-F(ab)-, anti-F(ab')2G-, anti-hinge autoantibodies). These autoantibodies have been shown to significantly affect the risk of chronic rejection and graft loss. Furthermore, clinical endpoints (patient and gaft survival, incidence of acute and chronic rejection, infectious diseases and graft function) up to 3 years will be analyzed.

Official Title
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Immunoglobulin Induction Therapy in Renal Transplant Recipients on Tacrolimus/Azathioprine or Tacrolimus/MMF: Effects on Th1, Th2, B Cell-/Monokine Responses and Immunoregulatory Autoantibody Levels

Conditions
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Renal Failure, Chronic, Renal Transplantation

Intervention / Treatment
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* Drug: intravenous immunoglobulins (IVIG)
* Procedure: kidney transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: renal transplant recipients of the Giessen renal transplant unit cadaveric and living renal transplants first and retransplants Exclusion Criteria: Contraindications against blood-taking (anaemia with hemoglobin < 9,5 g/l, hypotension) intravenous immunoglobulin therapy in the last half year before study entry Hyperimmunoglobulin therapy for severe CMV infection Pregnancy

Ages Eligible for Study
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Minimum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: intravenous immunoglobulins (IVIG)|nan|
|Procedure: kidney transplantation|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| patient survival |  | 1 year / 3 years / 5 years posttransplant | 
| graft survival |  | 1 year / 3 years / 5 years posttransplant | 
| acute rejection |  | 1 year | 
| chronic allograft nephropathy |  | 3 years / 5 years posttransplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| graft function |  | 1 year / 3 years / 5 years | 
| infectious complications |  | 1 year | 
| immunoglobulin levels |  | 1 year | 
| regulatory autoantibody levels |  | 1 year / 3 years / 5 years | 
| Th1 and Th2 responses |  | 1 year / 3 years | 
| B-cell/monocyte responses |  | 1 year / 3 years | 
| Expression of adhesion molecules, costimulatory molecules and cytokine receptors |  | 1 year / 3 years | 
| proteinuria (quantitative assessment) |  | 1 year / 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Th1, immunoglobulins, intravenous, kidney transplantation, acute rejection, chronic rejection, regulatory autoantibodies, Th2, B Cell, Monokines, Cytokine promoter gene polymorphisms