What this study adds
The combination of IPV > 30% and C0< 8 ng/mL during 3–12 months post-lung transplantation was
associated with higher risk of donor-specific antibodies and
mortality.
The impact of CYP3A5*3 polymorphism on C0 and
IPV was limited to the initial three months.
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 ofCYP3A5*3 polymorphism was only significant for C0and 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.