Effect of 3g Versus 2 g MMF in Combination With Tacrolimus on Progression of Renal Allograft Interstitial Fibrosis

Study Overview
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Brief Summary
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Development of chronic changes (scarring) in transplanted kidney tissue is a major cause of long-term kidney function deterioration and ultimately graft loss. It results from both immunologic and non-immunologic mechanisms. Mycophenolate mofetil (MMF) is immunosuppressive drug used for prevention of rejection after kidney transplant, usually in combination with a calcineurin inhibitor (tacrolimus or cyclosporine), with or without corticosteroids. Besides immunosuppression, MMF may also have direct antifibrotic properties. Tacrolimus has potent immunosuppressive effects and is the cornerstone of contemporary posttransplant immunosuppressive therapy in kidney recipients. However, it is also nephrotoxic. The hypothesis of the present study is that in the setting of similar net immunosuppression, higher dose of MMF (3 g daily) will result in slower progression of kidney fibrosis during first year posttransplant as compared to MMF 2 g daily. To test this hypothesis, the present study will randomly assign low immunological risk kidney transplant recipients to either 2g or 3 g MMF daily, in combination with tacrolimus, with, or without maintenance steroids. All patients will have kidney biopsy at implantation and at 12 months after transplantation. Main outcome will be 1-year change in chronic kidney histology (interstitial fibrosis) assessed by protocol biopsy.

Official Title
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Comparison of 3g Versus 2g Mycophenolate Mofetil in Combination With Tacrolimus on Progression of Chronic Histology Changes in Kidney Transplant Recipients

Conditions
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Kidney Transplantation, Kidney Failure

Intervention / Treatment
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* Drug: Mycophenolate mofetil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: first kidney or kidney-pancreas transplantation CDC PRA <=20% Exclusion Criteria: dual kidney transplantation AB0 incompatible transplantation 0 biopsy ci, ct, cv, or ah score >=2

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MMF 3g daily<br> | Drug: Mycophenolate mofetil<br>* Mycophenolate will be administered to all study patients at dose of 3 g daily for the first seven days posttransplant. Afterwards, study patients will continue, as randomized, on either 3 g, or 2 g MMF daily.<br>|
| Active Comparator: MMF 2 g daily<br> | Drug: Mycophenolate mofetil<br>* Mycophenolate will be administered to all study patients at dose of 3 g daily for the first seven days posttransplant. Afterwards, study patients will continue, as randomized, on either 3 g, or 2 g MMF daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression of interstitial fibrosis (ci) |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estimated glomerular filtration rate |  | 1 year | 
| Time to first acute rejection episode |  | up to 1 year | 
| Progression of other chronic scores |  | 1 year | 
| Graft loss |  | 1 year | 
| Patient survival |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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kidney transplantation, chronic allograft dysfunction, mycophenolate mofetil, Chronic