Is 3-hour cyclosporine blood level superior to trough level in early post-renal transplantation period?

Purpose: Cyclosporine dose is traditionally based on trough blood levels. C yclosporine trough blood level correlates poorly with acute rejection and c yclosporine nephrotoxicity after renal transplantation. We determined wheth er cyclosporine blood level at any other time point is superior to cyclospo rine trough blood level as a predictor of acute rejection and cyclosporine nephrotoxicity. Materials and Methods: Cyclosporine blood level was measured before (trough ), and 1, 2, 3 and 4 hours after the dose in 156 initial renal transplant c ases 2 to 4 days after the initiation of cyclosporine micro-emulsion formul a administration, The cylosporine micro-emulsion dose was based on cyclospo rine trough blood level targeting 250 to 400 mu g./l. Results: Regression analysis revealed that only delayed graft function (p = 0.007) and cyclosporine blood level after 3 hours (p = 0.008) predicted ac ute rejection. Mean cyclosporine trough blood level plus or minus standard error was not significantly different in patients with and without acute re jection (293 +/- 21 versus 294 +/- 11 mu g./l.). Mean cyclosporine blood le vel 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 tert iles at levels after 3 hours (1,100 and 1,500 mu g./l.). The group in which the level after 3 hours was less than 1,100 mu g./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 mu g./l. had the lowest acute rejection rate (5 of 46 pa tients, 11%) without increased cyclosporine nephrotoxicity (7 of 52 patient s, 13%). A level after 3 hours of greater than 1,500 mu g./l. was associate d 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-trans plantation period is associated with acute rejection and cyclosporine nephr otoxicity. A cyclosporine blood level range after 3 hours of 1,100 to 1,500 mu g./l. is associated with an optimal outcome. Our data suggest that cycl osporine blood level after 3 hours may represent a better method of monitor ing cyclosporine micro-emulsion dose than cyclosporine trough blood level. This hypothesis must be further studied in randomized trials.