Calcineurin Free Immunosuppression in Renal Transplant Recipients

• Kidney Transplantation
• Chronic Kidney Disease

• Drug: Sirolimus
  Loading dose 30 mg for three days, trough level of 10-20 ng/ml month 1-3, 8-15 ng/ml month 4 - 6
  Other Name: Rapamune
• Drug: Cyclosporine A
  Loading dose of 300 mg for three days, trough levels 250-300 ng/ml months 1-3, 150-250 ng/ml months 4 to 6
  Other Name: Sandimmun neoral
• Drug: Prednisone
  0.5 mg/kg, tapering every two weeks until 0.1 mg/kg
• Drug: Mycophenolate mofetil
  2 x 1000mg, through level above 2ug/ml
  Other Name: CellCept
• Procedure: Protocol biopsies
  protocol kidney biopsies at month one and three

• Experimental: Calcineurin free
  Immunosuppression with Sirolimus, Mycophenolate and Steroids
  Interventions:

  • Drug: Sirolimus
  • Drug: Prednisone
  • Drug: Mycophenolate mofetil
  • Procedure: Protocol biopsies
• Active Comparator: Calcineurin
  Immunosuppressive therapy with Cyclosporin A, Mycophenolate and Steroids
  Interventions:

  • Drug: Cyclosporine A
  • Drug: Prednisone
  • Drug: Mycophenolate mofetil
  • Procedure: Protocol biopsies

Inclusion Criteria:

• Male or female patients between 15 and 75 years of age, regardless of race.
• Female patients of child bearing age agree to maintain effective birth control practice during the study.
• Patient has end stage kidney disease and is a suitable candidate for primary renal transplantation or retransplantation as assessed by the transplantation center.
• Patient has been fully informed and has given written or independent person witnessed oral informed consent.

Exclusion Criteria:

• Patient is pregnant or breastfeeding.
• Patient has a low immunological risk constellation, defined by receiving a kidney from a HLA-identical related living donor.
• Patient has a high immunological risk constellation, defined as having within the previous three years a measured PRA grade of ?25% and/or having a previous graft survival shorter than 3 years due to rejection.
• Patient and donor have a positive T or B-cell crossmatch.
• Patient and donor are ABO incompatible.
• Age of donor > 68 years.
• Cold ischemia time > 36 hours.
• Patient has leucopenia, defined as having at transplantation less than 3000/mm3 leukocytes.
• Patient has thrombocytopenia, defined as having at transplantation less than 75000/mm3 thrombocytes.
• Patient is allergic or intolerant to cremophor RH 60 or structurally related compounds, steroids, Cyclosporine A Neoral, Rapamycin or MMF.
• Patient requires initial sequential or parallel therapy with immunosuppressive antibody preparation(s).
• Patient or donor is known to be HIV positive.
• Patient has significant liver disease, defined as having during the past 28 days continuously ASAT (SGOT) and/or ALAT (SGPT) levels greater than 3 fold of the upper value of the normal range of the investigational site.
• Patient with malignancy or history of malignancy ? 2 years, except non metastatic basal or squamous cell carcinoma of the skin that has been treated successfully.
• Patient has significant, uncontrolled concomitant infections and/or severe diarrhea, vomiting, or active peptic ulcer.
• Patient is taking or has been taking an investigational drug in the past 28 days.
• Patient has previously received or is receiving another organ transplant other than kidney.
• Patient is unlikely to comply with the visits schedule in the protocol.