Optimizing immunosuppressive drug dosing in pediatric renal transplantation. Part of a special series on Paediatric Pharmacology, guest edited by Gianvincenzo Zuccotti, Emilio Clementi, and Massimo Molteni

Abstract

Kidney transplantation in pediatric patients has become a successful and routine procedure, with overall 1-year patient and graft survival rates exceeding 95%. These success rates, however, are not maintained in the long-term, as reported 10-year graft survival rates are in the 50-60% range. Further improvement of long-term allograft survival in pediatric transplantation requires specific focus on long term complications such as increased cardiovascular risk and over-immunosuppression, two linked conditions. One approach to avoid inadequate immunosuppression is to more aggressively tailor immunosuppressive treatment based on individual patient needs. This strategy is currently pursued in the pediatric transplant setting by implementation of individualized therapeutic management of drug concentrations and total exposure. In addition, there is increasing evidence that pharmacogenetic testing may equally benefit individualized immunosuppressive therapy through the identification of SNPs and haplotypes predictive of encoding of proteins involved in drug transport, metabolism and response (efficacy/toxicity). The next challenge will be to provide real time web-based access to all patient information including pharmacokinetic, pharmacodynamic and genotyping data as part of a dosing algorithm or decision support tool with the ultimate goal to adaptively predict and control immunosuppressant exposure and response in individual patients to improve long-term outcomes after kidney transplantation.