Cyclosporine C2 monitoring improves renal dysfunction after lung transplantation

Background: Cyclosporine (CyA) toxicity is a potential cause of renal dysfunction, which occurs in 38% of lung transplant (LTx) recipients within 5 years. Reducing CyA to "sub-therapeutic" trough (CO) levels increases the risk of rejection. The 2-hour post-dose concentration (C2) is favored as the,best single-point surrogate measure of CyA area under the curve (AUC), which reflects drug exposure. In this investigation we assess the effect of conversion to CyA C2 monitoring on renal dysfunction after LTx. Methods: Fifteen patients (M:F = 12:3), aged 47 +/- 14 years (range 28 to 62), 3.5 +/- 2.7 (0.2 to 9.0) years post-LTx, with C0 in the therapeutic range (maintenance 100 to 200 mug/liters) (Behring/EMIT immunoassay) and abnormal renal function, were converted from CO monitoring to C2 monitoring with dose reductions targeting C2 levels of 300 to 600 mug/liter over a 12-month period. Results: CyA dose was reduced from 6.4 +/- 7.3 (1.2 to 27.9) to 3.1 +/- 2.7 (0.8 to 9.0) mg/kg/day (p = 0.04), with a reduction in C2 levels-from 799 341 (299 to 1,466) to 390 +/- 148 (195 to 675) mug/liter (p < 0.001). Improvements in serum creatinine (0.20 +/- 0.07 [0.12 to 0.35] vs 0.16 0.04 [0.11 to 0.22] mmol/liter [p = 0.005]) were maintained during the study follow-up period of 1 year. Only 1 patient developed acute rejection and group mean forced expiratory volume in 1 second (FEV1) remained stable (2.4 +/- 1.0 [1.1 to 4.0] vs 2.4 +/- 1.2 [1.1 to 4.6] liters). Conclusions: C2 monitoring is a practical method of improving renal dysfunction that allows safe dose reductions of CyA when formal AUC monitoring is not feasible. Extended use of this strategy is associated with long-term benefits.