C0 or C2 driven cyclosporine monitoring in long-term pediatric kidney transplant recipients: Is there any threat for chronic rejection development?

Abstract

The clinical management of cyclosporine has evolved greatly during the last decade thanks to the use of pharmacokinetic (PK) studies which confirmed the dose relationship between drug exposure and its biological effects. Therefore, cyclosporine PK monitoring during the early phase of the post-transplant period became essential to avoid over or underexposure to the drug thus preventing the risk of nephrotoxicity or acute rejection episodes. More recently, a simple PK determination based on cyclosporine blood concentration measured 2 h after the morning dose, has proven to be very effective for monitoring cyclosporine exposure in the early postoperative period. In this paper, the authors present a set of PK profiles obtained from a stable, long-term pediatric kidney transplant population and correlate these parameters with the risk of chronic rejection development. The study shows how cyclosporine monitoring based on the sole trough level determination misled a correct therapeutic behavior, as revealed by the PK parameters that were constantly below the therapeutic threshold in a small patient cohort who eventually developed chronic rejection. The C2 determination should be considered as the gold standard for cyclosporine monitoring in long-term pediatric recipients.