Abstract
BACKGROUND: It has previously been described that erratic tacrolimus blood levels are associated with graft failure in kidney and liver transplantation. Using a small cohort, we previously described that a higher tacrolimus standard deviation (SD) 6 to 12 months after lung transplantation increased the risk of chronic lung allograft dysfunction (CLAD) and death. We aimed to assess this in a larger cohort using the coefficient of variation (CoV) and identify potential risk factors for higher CoV. METHODS: We retrospectively reviewed 351 lung transplant recipients who received tacrolimus-based immunosuppression therapy. Cox proportional hazard modeling was used to investigate the effects of mean tacrolimus and CoV levels on survival and CLAD. RESULTS: Tacrolimus CoV from 6 to 12 months was independently associated with both CLAD (hazard ratio [HR], 19.99; 95% CI, 7.55-52.91; p < 0.001) and death (HR, 14.57; 95% (confidence interval) CI, 6.08-34.90; p < 0.001). Conversely, the mean trough tacrolimus blood concentration between 6 to 12 months was not associated with an increased risk of CLAD (HR, 0.94; 95% CI, 0.84-1.06; p = 0.34) or death (HR, 0.91; 95% CI, 0.82-1.01; p = 0.07). In a multivariable model, erratic tacrolimus levels were associated with antifungal use (β 0.10 95% CI 0.54-1.51, p < 0.001) and younger age (Î(2) -0.0015, 95% CI -0.17 to -0.03, p = 0.005 per 5 years). CONCLUSIONS: Erratic tacrolimus levels at 6 to 12 months post-lung transplant were associated with poor lung transplant outcomes. Future studies are required to determine whether interventions designed to optimize tacrolimus CoV could improve lung transplant outcomes.