Sirolimus Conversions in African-American Renal Transplant Recipients

• Drug: rapamune, mycophenolate mofetil and steroid

  At the time of transition patients randomized into this arm of the study will receive loading doses of sirolimus for two days and then 5mg PO daily. Twenty-four hour troughs will be checked per the schedule to ensure and monitor the therapeutic concentrations of 8-12ng/ml.

  Patients randomized into this arm of the study will continue their current dosing regimen and frequency of mycophenolate mofetil. Serum trough level monitoring of mycophenolic acid will not be performed unless clinically warranted per standard of care and dosage adjustments from such levels will be made only with consent of the study primary investigator.

  Other Names:

  • rapamune (Sirolimus)
  • mycophenolate mofetil (Cellcept)
• Drug: tacrolimus, sirolimus and steroid

  Tacrolimus dosing is based on 12-hour whole blood trough concentrations. Target blood concentration is 2-5 ng/ml.

  At the time of transition patients randomized into this arm of the study will receive loading doses of Sirolimus for two days and then 5mg PO daily. Twenty-four hour troughs will be checked per the schedule to ensure and monitor the therapeutic concentrations of 8-12ng/ml.

  Other Names:

  • tacrolimus (Prograf)
  • rapamune (Sirolimus)

• Active Comparator: Tacrolimus Withdrawal Arm

  At the time of transition patients randomized into this arm of the study will receive loading doses of sirolimus for two days and then 5mg PO daily. Twenty-four hour troughs will be checked per the schedule to ensure and monitor the therapeutic concentrations of 8-12ng/ml.

  Patients randomized into this arm of the study will continue their current dosing regimen and frequency of mycophenolate mofetil. Serum trough level monitoring of mycophenolic acid will not be performed unless clinically warranted per standard of care and dosage adjustments from such levels will be made only with consent of the study primary investigator.

  Intervention: Drug: rapamune, mycophenolate mofetil and steroid
• Active Comparator: Tacrolimus Minimization Arm

  Tacrolimus dosing is based on 12-hour whole blood trough concentrations. Target blood concentration is 2-5 ng/ml.

  At the time of transition patients randomized into this arm of the study will receive loading doses of Sirolimus for two days and then 5mg PO daily. Twenty-four hour troughs will be checked per the schedule to ensure and monitor the therapeutic concentrations of 8-12ng/ml.

  Intervention: Drug: tacrolimus, sirolimus and steroid

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Inclusion Criteria:

• At least 18 years of age and able to give informed consent
• African-American ethnicity
• Received a first or second non-ECD cadaveric or living donor renal transplant
• Transplant occurred during the past 6 to 24 weeks
• Patient has stable graft function, defined as no change of greater than 30% of baseline serum creatinine during the past month and no acute rejection in the past 6 weeks
• Estimated GFR using the modified MDRD equation of at least 40 mL/min10 at time of enrollment into the study
• Currently receiving tacrolimus, mycophenolate mofetil (at least 1 gm per day), and corticosteroids as their immunosuppression regimen.

Exclusion Criteria:

• Biopsy proven acute rejection episode that occurred within the past 6 weeks
• Malignancy within the past 3 years, except for non-melanoma skin cancer
• Any known intolerances to current immunosuppressant regimen necessitating withdrawal of the offending agent
• Currently enrolled in an investigational trial
• Woman of child bearing potential not utilizing an effective form of birth control
• Patients with uncontrolled dyslipidemia, defined at serum fasting LDL >200 mg/dL or serum fasting triglycerides >500 mg/dL.
• Patients with a spot urine protein to creatinine ratio of > 800 mg of protein per gram of creatinine.
• WBC < 3,000 cells/mm3
• Platelets < 100,000 cells/mm3