HIGHER CYCLOSPORINE LEVELS DECREASE KIDNEY REJECTION EPISODES WITHOUT INCREASING NEPHROTOXICITY

Abstract

303 PURPOSE: Cyclosporine has become the mainstay of immunosuppression for renal transplant patients. Controversy persists, however, regarding the optimal level of cyclosporine that should be maintained for maximum immunosuppressive benefits and minimal toxicity. Because acute rejection episodes have been shown to be predictive of chronic rejection and graft loss, the goal of this study was to evaluate whether higher cyclosporine levels in the early post-transplant period would reduce the number of acute rejection episodes without significantly increasing nephrotoxicity. METHODS: This study retrospectively reviewed all patients who had living donor or cadaveric kidney transplants during a 5.5 year period. Cadaveric recipients were induced with low dose OKT3 (2 mg/day × 12 days). All patients were maintained on triple drug therapy and divided into three groups. Group 1 (n=62) was maintained at lower cyclosporine levels (150-250 ng/ml), prednisone, and azathioprine. Group 2 (n=32) and Group 3 (n=25) were maintained at higher cyclosporine levels (250-350 ng/ml), prednisone, and either azathioprine (Group 2) or MMF (Group 3). High, low, and mean cyclosporine levels and serum creatinine levels at 1, 3, 6, and 12 months were recorded. The frequency and severity of acute rejection episodes, all pre-treatment biopsy proven, were reviewed at 3 and 12 months. RESULTS: There were 119 kidney transplant patients entered into the study. There were no significant differences in race, sex, age, previous transplants, number of mismatches, or preformed antibodies between groups. There were significantly fewer rejection episodes in the groups maintained at higher cyclosporine levels (Groups 2 and 3) during the first 3 months (p<0.001) as well as the first 12 months (p<0.017). There was no significant difference in mean creatinine levels at any time interval between groups. No statistically significant difference was seen in the severity of rejection episodes as determined by Banff criteria. Patients with low cyclosporine levels (Group 1) tended to have an increased number of readmission days within the first 12 months following transplant compared with patients in Groups 2 and 3 (8.2 vs. 5.0, respectively). CONCLUSION: Maintenance of cyclosporine at higher levels can reduce the number of acute rejection episodes. This benefit can be achieved without increasing cyclosporine nephrotoxicity (as measured by serum creatinine levels) and may reduce the need for readmission to the hospital.