Exploratory associations of tacrolimus exposure and clinical outcomes after lung transplantation: A retrospective, single center experience
European Journal of Clinical Pharmacology(2024)
摘要
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 (C 0 ) 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 C 0 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 C 0 and IPV on outcomes of interests, including de-novo donor-specific antibodies ( dn DSA), chronic lung allograft dysfunction (CLAD) and mortality. Results The influence of CYP3A5*3 polymorphism was only significant for C 0 and IPV during the first 3 months. Low C 0 (< 8 ng/mL) at 3–12 months increased the risk of dn DSA (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 C 0 /High IPV combination had significantly higher risks for dn DSA (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 C 0 or IPV alone. Conclusion A combination of Low C 0 /High IPV might be considered in categorizing patients towards risk of adverse clinical outcomes following lung transplantation.
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关键词
Tacrolimus,Lung transplantation,Chronic lung allograft dysfunction,Donor-specific antibody
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