ESPN 53rd Annual Meeting

ESPN 2021


 
Pharmacokinetics of tacrolimus in renal transplantation recipients during adolescence
Femke Vrieling-Prince 1 Romy Fleur van der Wouden 1 Karlien Cransberg 1 Antonia Bouts 2 Marlies Cornelissen 3 Joke Roodnat 4

1- Department of Paediatric Nephrology and Erasmus MC Transplant Institute, Erasmus MC Sophia Children’s Hospital, Rotterdam
2- Amsterdam UMC Emma Children’s Hospital, Paediatric Nephrology , Amsterdam
3- Radboud UMC Amalia Children’s Hospital, Paediatric Nephrology, Nijmegen
4- Department of Internal Medicine, Division of Nephrology and Erasmus MC Transplant Institute, Erasmus MC, Rotterdam
 
Introduction:

Adolescents have the highest risk of kidney transplant failure of all age groups. The objective of this study is to investigate the relation between puberty and the pharmacokinetic properties of tacrolimus after kidney transplantation.

Material and methods:

This study is part of the larger multicentre cohort study Adolesce-NT. Kidney transplant recipients aged between 8 -30 years were enrolled between 2012-2021. The study contains a pre-transplant and post-transplant patient group at time of inclusion. The variability of tacrolimus levels was calculated with all measurements 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. For each trough level we calculated the tacrolimus dose adjusted for weight.

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).

Results:

25 patients were included in the pre-transplant and 39 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.

Dose-adjusted trough levels increased linearly with increasing age, with higher increase for females compared to males. Intrapatient variability did not correlate significantly with stages of puberty (p=0.122) or gender (p=0.287).

Conclusions:

Our preliminary results indicate that the dose requirement to reach tacrolimus target levels is lower in adolescents, and in females.

We did not find a relationship between intrapatient variability as a measure of drug adherence and pubertal development. As we are in the process of including more patient data and adding data on drug compliance, future evaluations are expected to provide more information.