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OBJECTIVE Cyclosporine dose is traditionally based on trough blood levels. Cyclosporine trough blood level correlates poorly with acute rejection and cyclosporine nephrotoxicity after renal transplantation. We determined whether cyclosporine blood level at any other time point is superior to cyclosporine trough blood level as a predictor of acute rejection and cyclosporine nephrotoxicity. METHODS Cyclosporine blood level was measured before (trough), and 1, 2, 3 and 4 hours after the dose in 156 initial renal transplant cases 2 to 4 days after the initiation of cyclosporine micro-emulsion formula administration. The cylosporine micro-emulsion dose was based on cyclosporine trough blood level targeting 250 to 400 microg./l. RESULTS Regression analysis revealed that only delayed graft function (p = 0.007) and cyclosporine blood level after 3 hours (p = 0.008) predicted acute rejection. Mean cyclosporine trough blood level plus or minus standard error was not significantly different in patients with and without acute rejection (293+/-21 versus 294+/-11 microg./l.). Mean cyclosporine blood level after 3 hours was significantly lower in patients with acute rejection (1,156+/-90 versus 1,421+/-50, p = 0.008). Cases were divided into tertiles at levels after 3 hours (1,100 and 1,500 microg./l.). The group in which the level after 3 hours was less than 1,100 microg./l. had the highest acute rejection rate (22 of 50 patients, 44%) and a cyclosporine nephrotoxicity rate of 13% (7 of 52 patients). The group in which the level after 3 hours was 1,100 to 1,500 microg./l. had the lowest acute rejection rate (5 of 46 patients, 11%) without increased cyclosporine nephrotoxicity (7 of 52 patients, 13%). A level after 3 hours of greater than 1,500 microg./l. was associated with a rejection rate of 15% (7 of 47 patients) but significantly higher cyclosporine nephrotoxicity (16 of 52 patients, 30%). CONCLUSIONS Cyclosporine blood level after 3 hours in the early post-transplantation period is associated with acute rejection and cyclosporine nephrotoxicity. A cyclosporine blood level range after 3 hours of 1,100 to 1,500 microg./l. is associated with an optimal outcome. Our data suggest that cyclosporine blood level after 3 hours may represent a better method of monitoring cyclosporine micro-emulsion dose than cyclosporine trough blood level. This hypothesis must be further studied in randomized trials.
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