Kidney Failure, Kidney Transplantation
Conditions
Keywords
kidney transplantation, chronic allograft dysfunction, mycophenolate mofetil, Chronic
Brief summary
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.
Interventions
DRUGMycophenolate mofetil
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.
Sponsors
University Medical Centre Ljubljana
University Hospital Rijeka
Clinical Hospital Merkur
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. first kidney or kidney-pancreas transplantation 2. CDC PRA \<=20%
Exclusion criteria
1. dual kidney transplantation 2. AB0 incompatible transplantation 3. 0 biopsy ci, ct, cv, or ah score \>=2
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression of interstitial fibrosis (ci) | 1 year |
Secondary
| Measure | Time frame |
|---|---|
| Patient survival | 1 year |
| 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Frequency of BK viremia | 1 year | — |
| Frequency of BK nephropathy | 1 year | — |
| Development of donor-specific antibodies | 1 year | — |
| Renal morphology and hemodynamics assessed by ultrasound | 1 year | Subset of study patients |
| Frequency of infections requiring hospitalization | 1 year | — |
| Frequency of CMV viremia | 1 year | — |
Countries
Croatia
Outcome results
None listed