CYCLOSPORINE TROUGH CONCENTRATIONS IN PREDICTING ALLOGRAFT-REJECTION AND RENAL TOXICITY UP TO 12 MONTHS AFTER RENAL-TRANSPLANTATION

Study Objective. To evaluate the utility of cyclosporine (CsA) trough concentrations as a monitoring tool for acute graft rejections and CsA nephrotoxicity.Design. Retrospective chart review. Setting. Universit y-affiliated teaching hospital. Patients. One hundred thirty-seven adu lts who had undergone kidney transplantation. Measurements and Main Re sults. Clinical data extracted from the charts were CsA dosage, CsA tr ough levels (whole blood, HPLC method), biopsy findings to confirm acu te rejections, and serum creatine to determine clearance by the Jellif fe method. Data were collected at up to 1 month, between 1 month and 3 months, and between 3 and 12 months after transplantation. For each t ime period, receiver's operating characteristics curves were generated to identify the optimum CsA concentration for avoiding acute rejectio n and CsA. nephrotoxicity. At up to 1 month, the CsA therapeutic respo nse threshold was 182 ng/ml (sensitivity 69%, specificity 84%, p<0.000 1) and toxicity threshold for CsA nephrotoxicity was 204 ng/ml (sensit ivity 89%, specificity 56%, p<0.0001). Between 1 month and 3 months, t he respective figures were 175 ng/ml (sensitivity 58%, specificity 89% , p<0.0002) and 189 ng/ml (sensitivity 87%, specificity 65%, p<0.0001) . Between 3 and 12 months, the CsA therapeutic response threshold decr eased to 135 ng/ml (sensitivity 56%, specificity 40%, p>0.1) and the t oxicity threshold for CsA nephrotoxicity remained relatively static at 204 ng/ml (sensitivity 100%, specificity 14%, p<0.0001). Conclusion. Early in CsA therapy it is essential to prevent graft rejection. Drug concentrations exceeding approximately 182 ng/ml threshold accomplish this goal. Later, successful therapy demands that CsA nephrotoxicity b e avoided. This goal is accomplished by not exceeding a CsA concentrat ion of 204 ng/ml.