AUTHOR=Marquet Pierre , Anglicheau Dany , Humeau Antoine , Adrouche Sofian , Saada Lakhdar , Bisiaux Julie , Guillemin Sara , Lardy-Cléaud Audrey , Rostaing Lionel 

TITLE=Tacrolimus Dose Requirement in De Novo Adult Kidney Transplant Patients Treated With Adoport® Can Be Anticipated

JOURNAL=Transplant International

VOLUME=37

YEAR=2024

URL=https://www.frontierspartnerships.org/journals/transplant-international/articles/10.3389/ti.2024.13495

DOI=10.3389/ti.2024.13495

ISSN=1432-2277

ABSTRACT=<p>All the factors potentially influencing tacrolimus dose requirement and combinations thereof have never been thoroughly investigated, precluding accurate prediction of tacrolimus starting dose. This prospective, non-interventional, multicenter study in <italic>de novo</italic> adult kidney transplant recipients over the first year after transplantation aimed to investigate the factors influencing tacrolimus dose-standardized trough blood concentration (C<sub>0</sub>/D) over the first week post-transplant (D4-D7, primary objective), D8-M3 and M3-M12 (secondary objectives). Statistical analysis employed mixed linear models with repeated measures. Eighteen sites enrolled 440 patients and followed them up for 9.5 ± 4.1 months. Age at baseline (<italic>p</italic> = 0.0144), end-stage renal disease (<italic>p</italic> = 0.0092), CYP3A phenotype (<italic>p</italic> &lt; 0.0001), dyslipidemia at baseline (<italic>p</italic> = 0.0031), hematocrit (<italic>p</italic> = 0.0026), total bilirubin (<italic>p</italic> = 0.0261) and plasma creatinine (<italic>p</italic> = 0.0484) independently increased with log(C<sub>0</sub>/D) over D4-D7, explaining together 72.3% of the interindividual variability, and representing a robust model to estimate tacrolimus initial dose. Donor age and CYP3A phenotype were also influential over D8-M3 and M3-12, in addition to recipient age. Corticosteroids, diabetes at baseline, and ASAT yielded inconstant results between D8-M3 and M3-M12. We found no ethnicity effect when CYP3A phenotype was accounted for, and no food effect. Intra-individual variability over M3-M12 was moderate, and significantly lower in patients with chronic hepatic disorder (<italic>p</italic> = 0.0196) or cancer (<italic>p</italic> = 0.0132).</p>