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- Title
Exploratory associations of tacrolimus exposure and clinical outcomes after lung transplantation: A retrospective, single center experience.
- Authors
Du, Wenwen; Wang, Xiaoxing; Zhang, Dan; Zuo, Xianbo
- Abstract
Purpose: This study aimed to investigate the potential impact of tacrolimus (TAC) exposure on clinical outcomes after lung transplantation. Methods: This retrospective observational study enrolled a total of 228 lung transplant recipients. TAC trough levels (C0) were collected for 3 intervals: 0–3 months, 3–12 months, and 12–24 months. The intra-patient variability (IPV) was calculated using coefficient of variation. Genotyping of CYP3A5*3 (rs776746) was performed. Patients were further divided into groups based on the C0 cut-off value of 8 ng/mL and IPV cut-off value of 30%. Cox proportional hazards regression models were used to explore the potential impact of C0 and IPV on outcomes of interests, including de-novo donor-specific antibodies (dnDSA), chronic lung allograft dysfunction (CLAD) and mortality. Results: The influence of CYP3A5*3 polymorphism was only significant for C0 and IPV during the first 3 months. Low C0 (< 8 ng/mL) at 3–12 months increased the risk of dnDSA (hazard ratio [HR] 2.696, 95% confidence interval [CI] 1.046–6.953) and mortality (HR 2.531, 95% CI 1.368–4.685), while High IPV (≥ 30%) during this period was associated with an increased risk of mortality (HR 2.543, 95% CI 1.336–4.839). Patients with Low C0/High IPV combination had significantly higher risks for dnDSA (HR 4.381, 95% CI 1.279–15.008) and survival (HR 6.179, 95% CI 2.598–14.698), surpassing the predictive power provided by C0 or IPV alone. Conclusion: A combination of Low C0/High IPV might be considered in categorizing patients towards risk of adverse clinical outcomes following lung transplantation.
- Subjects
MORTALITY; LUNG transplantation; PATIENTS; TRANSPLANTATION of organs, tissues, etc.; RESEARCH funding; SCIENTIFIC observation; TREATMENT effectiveness; RETROSPECTIVE studies; DESCRIPTIVE statistics; HOMOGRAFTS; GRAFT rejection; GENETIC polymorphisms; TACROLIMUS; RESEARCH; CONFIDENCE intervals; GENOTYPES; PROPORTIONAL hazards models
- Publication
European Journal of Clinical Pharmacology, 2024, Vol 80, Issue 5, p747
- ISSN
0031-6970
- Publication type
Article
- DOI
10.1007/s00228-024-03640-6