1. Pharmacokinetics of tacrolimus in paediatric renal transplantation recipients during adolescence

F.H.M. Prince, J.I. Roodnat, R.F. van der Wouden, E.A.M. Cornelissen, A.H. Bouts, C.C. Baan, A.C.S. Hokken-Koelega, T. van Gelder, K. Cransberg

Wednesday 4 march 2020

0:00 - 0:00h at Toon Hermans Foyer

Parallel session: Postersessie 1 – Klinische abstracts

Background: Adolescents have a higher risk of kidney transplant failure, regardless of the age at transplantation. The effects of changing hormonal parameters may influence the pharmacokinetics. In this study we investigated the relation between pubertal development and pharmacokinetic properties of tacrolimus among children after kidney transplantation.

Methods: This pharmacokinetics study is embedded in the prospective multicenter observational Adolesce-NT study. Kidney transplant recipients aged between 8 and 30 years were enrolled between 2012 and 2018. The study contains a pre-transplant and a post-transplant patient group at time of inclusion. The tacrolimus levels measured from 6 months till 1 year after transplantation in the pre-transplant group and from inclusion till 1 year later in the post-transplant group were used to calculate the variability. The levels at the beginning of the study period were used to calculate the dose adjusted trough level.

Exclusion criteria: no informed consent, pubertas praecox, treatment with rituximab or ATG and no tacrolimus. Our primary outcome parameters are the dose-adjusted trough level and the intrapatient variability. We compared these pharmacokinetic parameters to puberty staging and gender, and corrected for confounders (including eGFR, steroid use, CYP3A4 and CYP3A5 polymorphisms) with linear regression analysis.

Results: 25 patients were included in the pre-transplant and 35 patients in the post-transplant group. When corrected for confounders, we found a significant correlation between puberty staging and the dose-adjusted trough level (p= 0.017). There was a linearly increase of the dose-adjusted trough levels by increasing age. The dose-adjusted trough level seemed to increase with a higher rate for females compared to males. We found no significant relation between the intrapatient variability and stages of puberty (p=0.122) or gender (p=0.287).

Conclusions: Our results indicate that the same trough level is reached with lower relative doses of tacrolimus with progression of adolescence and for females. We did not find a relationship between variability as a measure of adherence and pubertal development. As we aim to include more patients and add data on drug compliance, future evaluations will provide more information.