Open Label Comparative Study Of De Novo Renal Allograft Recipients Receiving CSA + MMF + Corticosteroids Versus CSA + Rapamune + Corticosteroids

• Drug: CsA+Rapamune+CS
  Part 1: Rapamune will be given as a loading dose of 6 mg once followed by maintenance dose of 2 mg to achieve a target trough level of 8-15 ng/ml. Part 2: Rapamune dose will be adjusted to achieve a target trough level of 10-15ng/ml through 6 months
• Drug: CsA+MMF+CS

  The control arm is the standard local practice (official protocol) in Iran:

  Cyclosporine + MMF + Corticosteroid. The time period is from pre-study screening / baseline evaluation up to 12 months for patients who are maintained on CsA + MMF + CS.

• Active Comparator: Arm A (CsA+Rapamune+CS)
  Intervention: Drug: CsA+Rapamune+CS
• Experimental: Arm B (CsA+MMF+CS)
  Intervention: Drug: CsA+MMF+CS

Inclusion Criteria:

• Age 13 years and weight 40 kg
• End-stage renal disease, with patients receiving a primary or secondary renal allograft from a living-unrelated donor, or from a living-related donor.
• Women who are of childbearing potential must have a negative pregnancy test before enrollment in the study and agree to use a medically acceptable method of contraception throughout the treatment period and for 3 months following discontinuation from the study.
• Total white blood cell count 4.0 x 109/L (4,000/mmP3P), platelet count 100 x 10P9P/L(100,000/mmP3P), fasting triglycerides ? 4.6 mmol/L (400 mg/dL), fasting cholesterol ? 7.8 mmol/L (300 mg/dL). If it is not possible to obtain fasting triglycerides and cholesterol before surgery, historical values (within 1 year) may be used.
• Signed and dated informed consent (parent or legal guardian must provide consent for patients <18 years of age). An assent form will be signed by patients < 18 years of age enrolled in the study.

Exclusion Criteria:

• Evidence of active systemic or localized major infection at the time of initial Sirolimus administration.
• Cadaveric donors
• History of malignancy within 5 years before enrollment into the study (with the exception of adequately treated basal cell or squamous cell carcinoma of the skin)
• Use of any investigational drug other than specified in the protocol during the 4 weeks before enrolling in the study.
• Use of planned antibody induction therapy at the time of transplantation.
• Active gastrointestinal disorder that may interfere with drug absorption.
• Known hypersensitivity to Sirolimus, MMF or Cyclosporine or its derivatives.
• Multiple organ transplants (2 or more organ transplant e.g. Kidney and Pancreas).
• Patient with high risk of rejection (eg. Patients with a PRA >50%, black patients and patients with 2nd transplant who lost their first graft within the first 6 months).
• Evidence of infiltrate, cavitation, or consolidation on chest x-ray obtained during pre-study screening