TACROLIMUS/“LOW-DOSE” MYCOPHENOLATE MOFETIL VS. MICRO-EMULSION CYCLOSPORINE/ “LOW-DOSE” MYCOPHENOLATE MOFETIL AFTER KIDNEY TRANSPLANTATION-1 YEAR FOLLOW-UP OF A PROSPECTIVE, RANDOMIZED CLINICAL TRIAL.

Abstract

14 The superior immunosuppressive properties of tacrolimus, micro emulsion cyclosporine (neoralR), and mycophenolate mofetil (MMF 2 and 3 gram) have been demonstrated in several recent clinical trials involving solid organ transplants. In this prospective, randomized study, we compared tacrolimus/“low-dose” MMF (TMBIR) and neoralR /“low-dose” MMF (NMBIR) based immunosuppressive regimens after kidney transplantation. Fifty three consecutive adult recipients of renal transplant were randomized to receive either tacrolimus (0.08 mg/kg/bid) (n=27) or neoralR (4 mg/kg/bid)(n=26) orally, started pre-operatively and continued if allograft demonstrated no post-operative acute tubular necrosis(ATN). Cytolytic antibody therapy was allowed in case of post-operative ATN. Both groups received similar “low-dose” MMF (500 mg/bid) and steroid (2 mg/kg/day to taper off after 1 year). Switch from tacrolimus to neoralR or vice versa was allowed after refractory rejection or severe adverse events. Patients were followed for 1 year for patient and graft survival and incidence of acute rejection. Both groups (TMBIR vs. NMBIR) were equally matched with respect to: patient's age (46.5±2.6 vs. 46.8±2.4 yr.), donor's age (37.1±2.7 vs. 38.8±3.2 yr.), Male (52 vs. 69%), Caucasian (81 vs. 92%), causes of ESRD, months on dialysis(25.8±5.9 vs. 31.6±7.5), panel reactive antibody (9.6±4.1 vs. 9±5.1%), HLA mismatch, cold ischemia time (14.4±1.5 vs. 15±1.6 hours), and type of transplant (cadaver: 66.6 vs. 76%), respectively. 1 year patient survival rates were 88.9% for TMBIR and 100% for NMBIR (p=ns) and 1 year graft survival rates were 88.9% for TMBIR and 96.1 for NMBIR (p=ns). There was no significant difference in the incidence of biopsy confirmed acute rejection: 14.8% (4/27) TMBIR and 23% (6/26) NMBIR patients, of these, steroid resistant rejections requiring cytolytic antibody therapy were higher in NMBIR group [50% (3/6) vs. 25% (1/4) p=ns]. 3 patients crossed over from NMBIR to TMBIR for refractory rejections and 1 patient crossed over from TMBIR to NMBIR for new onset seizure. There were 4 episodes of CMV infections all in TMBIR. Other infections, hematologic, and electrolyte abnormalities, post-transplant diabetes (1 in each group), neurologic, muskulo-skeletal, and gastrointestinal adverse events were similar in both groups. One patient in NMBIR developed malignant melanoma. Overall, our data show that both tacrolimus and micro-emulsion cyclosporine(neoralR) in combination with “low-dose” mycophenolate mofetil provide effective and comparable immunosuppression and have similar adverse events in kidney transplant recipients. TMBIR was associated with higher episodes of CMV infections.