TACROLIMUS EXPOSURE AND ACUTE KIDNEY INJURY ACCORDING TO

@article{costajunior2026tacrolimus,
  title = {{TACROLIMUS EXPOSURE AND ACUTE KIDNEY INJURY ACCORDING TO}},
  author = {Luiz Carlos da COSTA-JUNIOR and Amanda Melo Leite LEãO and Marina IZU and Yasmim Gabriele MATOS and Rita de Cássia Barbosa da Silva TAVARES and Simone Cunha MARADEI and Maria Claudia Rodrigues MOREIRA and Giovana Fernanda Santos FIDELIS and Julia Tiemi SIGUEMOTO and Ighor Seiji Okumura TIODA and Pedro Gamberini MARTINS and Eder De Carvalho PINCINATO and Matilde ROMERO and Renata BINATO and Decio LERNER and Patrícia MORIEL and Teresa De Souza FERNANDEZ and Paulo Caleb Júnior Lima SANTOS},
  journal = {Hematology, Transfusion and Cell Therapy},
  year = {2026},
  month = oct,
  doi = {10.1016/j.htct.2026.108431},
  url = {https://doi.org/10.1016/j.htct.2026.108431},
  note = {CC BY},
}

TY  - JOUR
TI  - TACROLIMUS EXPOSURE AND ACUTE KIDNEY INJURY ACCORDING TO
AU  - Luiz Carlos da COSTA-JUNIOR
AU  - Amanda Melo Leite LEãO
AU  - Marina IZU
AU  - Yasmim Gabriele MATOS
AU  - Rita de Cássia Barbosa da Silva TAVARES
AU  - Simone Cunha MARADEI
AU  - Maria Claudia Rodrigues MOREIRA
AU  - Giovana Fernanda Santos FIDELIS
AU  - Julia Tiemi SIGUEMOTO
AU  - Ighor Seiji Okumura TIODA
AU  - Pedro Gamberini MARTINS
AU  - Eder De Carvalho PINCINATO
AU  - Matilde ROMERO
AU  - Renata BINATO
AU  - Decio LERNER
AU  - Patrícia MORIEL
AU  - Teresa De Souza FERNANDEZ
AU  - Paulo Caleb Júnior Lima SANTOS
PY  - 2026
DA  - 2026/10/23
JO  - Hematology, Transfusion and Cell Therapy
DO  - 10.1016/j.htct.2026.108431
UR  - https://doi.org/10.1016/j.htct.2026.108431
AB  - Introduction: Pediatric allogeneic hematopoietic cell transplantation (allo-HCT) recipients pose challenges for tacrolimus (TAC) management because age-related pharmacokinetic (PK) variability often requires higher weight-adjusted doses, whereas excessive early exposure may increase nephrotoxicity. CYP3A5 expression is a major determinant of TAC metabolism and is incorporated into Clinical Pharmacogenetics Implementation Consortium (CPIC) genotype-guided dosing recommendations; however, its impact on TAC exposure and early toxicity in pediatric HCT remains poorly defined. Objective: To evaluate the applicability of CPIC-defined CYP3A5 phenotypes in pediatric allo-HCT recipients receiving TAC, focusing on TAC exposure and early clinical outcomes. Methods: This retrospective single-center exploratory study included patients aged < 18 lt; 18 years who received TAC-based graft-versus-host disease (GVHD) prophylaxis after allo-HCT between 2015 and 2023. TAC exposure from D1 to D21 was assessed using concentrations, weight-adjusted doses, and concentration-to-dose (C/D) ratios. Acute kidney injury (AKI) was defined according to KDIGO 2012 serum creatinine criteria. Genotyping used the Illumina Infinium Global Diversity Array with Enhanced PGx content and DRAGEN processing. CYP3A5 phenotypes were classified according to CPIC as normal, intermediate, or poor metabolizers and by expressor status. Groups were compared using chi-square or Fisher's exact tests and the Mann-Whitney U test, as appropriate, in SPSS v21. The study was ethics-approved and conducted in accordance with the Declaration of Helsinki. Results: Twenty-four pediatric TAC-treated allo-HCT recipients were included; 54.2% were female, 58.3% Brown, 33.3% White, and 8.3% Black. Diagnoses included ALL (41.7%), BMF (25.0%), AML (20.8%), CML (4.2%), and lymphoid/plasma cell malignancies (8.3%). Bone marrow was the predominant graft source (91.7%); donors were haploidentical (50.0%), MURD (25.0%), MRD (20.8%), and MMURD (4.2%). Conditioning intensity was evenly distributed between RIC and MAC, and total body irradiation was used in 83.3% of cases. No patient was a CYP3A5 normal metabolizer; 37.5% were intermediate metabolizers/expressors and 62.5% poor metabolizers/non-expressors. D1–D21 AKI occurred in 45.8% of recipients, including KDIGO stage 2–3 AKI in 16.7%. AKI occurred in 73.3% of poor metabolizers/non-expressors, whereas no events were observed among intermediate metabolizers/expressors (p < 0.001). KDIGO stage 2–3 AKI occurred in 26.7% of poor metabolizers/non-expressors, with no events observed in the intermediate metabolizer/expressor group (p = 0.090). Poor metabolizers/non-expressors had higher TAC concentrations during the third week after HCT, with mean ranks of 12.46 and 6.86, respectively (p = 0.043). Overall median TAC concentrations were 10.5 and 7.2 ng/mL, respectively (p = 0.161). Median weight-adjusted TAC doses were 0.019 and 0.021 mg/kg, respectively (p = 0.788), and median C/D ratios were 484.5 and 620.1, respectively (p = 0.421). Conclusion: In this exploratory pediatric allo-HCT cohort, the CPIC-defined CYP3A5 poor metabolizer/non-expressor phenotype was associated with early AKI and higher third-week TAC concentrations despite similar dosing. These findings support CYP3A5-guided dosing, combined with intensified early therapeutic drug monitoring, for nephrotoxicity risk stratification. Larger cohorts are needed to determine whether this strategy may meaningfully reduce early AKI.
SN  - 2531-1379
SN  - 2531-1387
ER  -