Kidney Diseases
Conditions
Keywords
kidney transplantation, immunosuppression, calcineurin inhibitor, sirolimus, chronic allograft nephropathy
Brief summary
This study was done to find out which treatment, tacrolimus or sirolimus, leads to better long-term kidney function in kidney transplant patients.
Detailed description
The aim of this study was to compare the complete avoidance of calcineurin inhibitors (CI) using a sirolimus-based immunosuppressive regimen to a tacrolimus-based regimen in kidney transplantation. This study was a prospective open-label trial randomizing patients to receive tacrolimus, mycophenolate mofetil and prednisone or sirolimus, mycophenolate mofetil and prednisone. All patients received antithymocyte globulin induction. All rejection episodes were proven by biopsy. The hypothesis was that CI free immunosuppression after kidney transplantation will lead to an increase in glomerular filtration rate (GFR) at one year after kidney transplantation.
Interventions
DRUGAnti-thymocyte globulin
Thymoglobulin 1.5 mg/kg/d (days 0,1,2,4,6)
DRUGMycophenolate mofetil
Mycophenolate mofetil 750 mg p.o. b.i.d.- maintenance
DRUGPrednisone
Prednisone 500 mg/day initially, tapered to 5 mg/day by day 92
DRUGTacrolimus
Tacrolimus - maintain trough levels of 6-8 ng/ml (whole blood Imx assay)
DRUGSirolimus
Rapamycin 3 to 5 mg/day; adjust to the high-performance liquid chromatography (HPLC) blood level 15 to 20 ng ml
Sponsors
Wyeth is now a wholly owned subsidiary of Pfizer
Genzyme, a Sanofi Company
Roche Pharma AG
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Living and deceased donor kidney transplant recipients at the Mayo Clinic, Rochester, Minnesota
Exclusion criteria
* Patients with type 1 diabetes less than 50 years of age who receive a living donor kidney transplant followed by a pancreas transplant * Pediatric patients (\<18 years of age) * Multi-organ transplants (e.g., kidney-pancreas, kidney-liver) * ABO-incompatible or positive crossmatch recipients (ABO incompatibility is an immune system reaction that occurs when blood from two different and incompatible blood types are mixed together.) * Patients with severe hyperlipidemia (serum cholesterol \>350 mg/dl or serum triglycerides \>500 mg/dl * Patients with severe leukopenia (White Blood Cell count \[WBC\]\<3000 10\^3/ml) * Patients unwilling to return to the transplant center for late follow-up visits * Body mass index (BMI) ≥ 32 with incisional problems post transplant (as determined by renal transplant surgeon
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glomerular filtration rate (GFR) (iothalamate clearance) at 12 months following transplantation | 12 months following transplantation | Glomerular filtration rate (Iothalamate clearance) at 12 months following transplantation. |
Secondary
| Measure | Time frame |
|---|---|
| GFR (iothalamate clearance) at other time points | 24 months |
| Other measures of renal function (serum creatinine, proteinuria and albuminuria) | 24 months |
| Acute rejection both early and after tacrolimus withdrawal | 24 months |
| Patient and graft survival | 24 months after transplantation |
| Complications-especially hypertension, diabetes, dyslipidemia | 24 months |
Countries
United States
Outcome results
None listed