Adequate early cyclosporin exposure is critical to prevent renal allograft rejection: patients monitored by absorption profiling

Abstract

This study used receiver operating characteristic analysis to investigate the properties of area under the concentration-time curve during the first 4h after cyclosporin-microemulsion dosing (AUC0-4) and cyclosporin (CyA) levels immediately before and at 2 and 3h after dosing (C0, C2 and C3) to predict the risk of biopsy-proven acute rejection (AR) at 6 months. Ninety-eight kidney transplant recipients treated with CyA-microemulsion-based triple therapy immunosuppression were studied on post-transplant days 3, 5, and 7, and at increasing intervals thereafter. The most sensitive and specific predictor of AR was AUC0-4. Of the single time-point measurements, the measurement properties of C2 were closest to those of AUC0-4, and superior to those of C3. The relationship between C0 and subsequent AR was weak and did not reach statistical significance. On day 3, CyA AUC0-4 > or = 4,400 ng.h/mL and C2 > or = 1,700 ng/mL were each associated with a 92% negative predictive value for rejection in the first 6months. Pharmacokinetic measurements on or after day 5, and measurements on day 3 in patients with delayed graft function, were not predictive of AR. Adequate exposure within the first 3days post transplantation may be critically important in preventing subsequent rejection.