Erratic tacrolimus levels at 6 to 12 months post-lung transplant predicts poor outcomes

Résumé fourni par la source

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) 6-12 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 modelling was used to investigate the effects of mean tacrolimus and CoV levels on survival and CLAD. Results Tacrolimus CoV from 6-12 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% CI, 6.08-34.90; p<0.001). Conversely, the mean trough tacrolimus blood concentration between 6-12 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 anti-fungal use (β 0.10 95% CI 0.54 – 1.51, p<0.001) and younger age (Î ² -0.0015, 95% CI -0.17 - -0.03, p=0.005 per 5 years). Conclusion Erratic tacrolimus levels at 6-12 months post lung transplant were associated with poor lung transplant outcomes. Future studies are required to determine whether interventions designed to optimize tacolimus CoV could improve lung transplant outcomes.

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