Kidney Biopsy Controlled Trial of Calcineurin Inhibitor Withdrawal
Condition: Kidney Transplantation
Intervention: Kidney Biopsy; Rapamune (sirolimus/rapamycin); Tacrolimus
Intervention description: Skin over the kidney will be cleansed and disinfected. The skin and deeper tissue will be numbed with novocaine like solution. A special needle will be inserted guided by ultrasound into the kidney for an instant to withdraw the small specimen.; Rapamune will be given at a dose of 5mg/day for two days beginning at the initiation of tacrolimus reduction. Thereafter, Rapamune will be given at a dose of 3 mg/day. The dose of Rapamune will be titrated to achieve a blood level (by HPLC) between 5 and 10 for the duration of the study.; Patients in this group will continue to receive tacrolimus at reduced doses. Doses will be titrated to achieve tacrolimus trough blood levels between 4 and 6. Myfortic at doses of 720 mg BID and steroids will be continued for the duration of the study (12 months).
Intervention MeSH terms: Sirolimus; Tacrolimus
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 58.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Kidney Transplant; Immunosuppression drugs; Rapamune; tacrolimus; calcineurin inhibitor; Kidney Biopsy, Needle

Summary:

      Current therapy to prevent organ rejection relies on the use of calcineurin inhibitors either
      cyclosporine or tacrolimus. Although these agents have been very successful in preventing
      early acute rejection, this success has not translated into improved long-term kidney
      transplant function. One of the important factors that leads to premature kidney transplant
      failure is chronic allograft nephropathy (CAN). CAN is characterized by progressive
      interstitial fibrosis or "scarring", vascular wall thickening, and finally glomerular
      sclerosis leading to slow progressive loss of kidney function. Calcineurin inhibitors have
      been shown to play an important role in the pathogens of CAN. Renal transplant recipients in
      whom calcineurin inhibitors are discontinued enjoy better and longer kidney function.
      Therefore, immunosuppressive strategies are being designed with the intention of withdrawing
      calcineurin inhibitors.

      The purpose of this trial is to test if tacrolimus can be safely substituted by sirolimus
      (Rapamycin) and this substitution will yield improved renal function, less CAN and better
      graft survival rates over the first year.
    

Eligibility criteria:

        Inclusion Criteria:

          1. All patients receiving their first renal allograft transplant will be considered
             eligible for study

          2. Patients receiving both living and cadaveric donors will be eligible

        Exclusion Criteria:

          1. If less than 18 years of age

          2. Severe hyperlipidemia

          3. If pregnant or cannot comply with proper birth control during the study

          4. Recipients of kidney together with another solid organ or bone marrow transplant

          5. Patients receiving any investigational medications or participating in a clinical
             trial

          6. Patients receiving a second or third renal allograft

          7. PRA > 30%

          8. Active infections

          9. Chronic antiarrhythmic therapy for ventricular arrhythmia

         10. Malignancy except for basal cell carcinoma

         11. HIV

         12. ANC count < 1,000/ mm3, Platelet count < 100,00/mm3

         13. Fasting triglycerides > 400 mg/dl and cholesterol > 300 mg/dl

         14. HCV-positive, HBVSAg-positive, HBVCoreAb-positive and HBVSAntibody negative or HCV/HBV
             co-infected patients

         15. Breastfeeding women