Biomarkers related to immunosuppression in pediatric kidney transplantation
摘要
After kidney transplantation, there is the lifelong need to take immunosuppressive drugs, most of which have a narrow therapeutic window and a high inter- and intra-patient variability, entailing the risk of over- and under-immunosuppression. This balance is specifically challenging in pediatric recipients due to age-specific challenges, such as infections, a developing immune system, their continuously changing body composition, and their longer life expectancy. Currently, the balance leans more towards over-immunosuppression, given the low incidence of rejection and high incidence of (opportunistic) infections, highlighting the need to improve our immunosuppressive strategy. The pharmacokinetic parameters used for therapeutic drug monitoring, such as trough and peak serum levels or area-under-the-concentration-time-curve measurements, do not fully reflect the degree of immunosuppression and were primarily established to prevent under-immunosuppression. The addition of pharmacodynamic biomarkers enables effect-related drug monitoring, allowing for better personalized immunosuppression strategies. Over the last decade, multiple pharmacodynamic biomarkers have been identified and tested, monitoring the suppression of the recipients’ immune system. We have summarized the rationale, evidence, and limitations regarding the clinical use of these pharmacodynamic biomarkers. In conclusion, we stimulate the use of pharmacodynamic biomarkers in pediatric kidney transplant recipients, of which torque teno virus loads, virus-specific T cells, donor-specific antibodies, and donor-derived cell-free DNA appear promising. However, their specific indications, limitations, and costs should be considered. We encourage prospective interventional trials investigating the added effect of these biomarkers in personalizing therapeutic drug dosing, ultimately avoiding over- and under-immunosuppression and thus preventing infections, malignancy, toxicity, and rejection.
Graphical abstract