Exploratory associations of tacrolimus exposure and clinical outcomes
after lung transplantation: a retrospective, single center experience
Abstract
Aims: 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 234 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 donor-specific antibodies (DSA), 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 DSA (hazard ratio [HR]
2.820, 95% confidence interval [CI] 1.093–7.276) and mortality (HR
2.220, 95% CI 1.162–4.243), while High IPV (>=30%)
during this period was associated with an increased risk of mortality
(HR 2.100, 95% CI 1.120–3.937). Patients with Low
C0/High IPV combination had significantly higher risks
for DSA (HR 4.534, 95% CI 1.326–15.507) and survival (HR 4.205, 95%
CI 1.739–10.168), 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.