Time to Therapeutic Tacrolimus Levels and Association with Acute Cellular Rejection and De Novo Donor-Specific Antibody Development in Lung Transplant Recipients

Purpose Tacrolimus (FK506) is standard of care for preventing rejection in lung transplant (LTx) for maintenance immunosuppression. Both acute cellular rejection (ACR) and de novo donor-specific antibodies (dnDSAs) are strongly associated with development of chronic lung allograft dysfunction. Time to therapeutic FK506 has not been standardized. We evaluated whether time to therapeutic FK506 impacted ACR and dnDSA rates within 6 months (M) of LTx. Methods We reviewed LTx recipients between 5/2016 - 12/2019. We excluded patients who did not receive FK506, received their first dose ≥48 hours post-LTx, were transitioned off FK506 during the study period, or expired within 30 days (d). Primary outcome was a composite of ACR and dnDSA development within 6M for patients achieving therapeutic FK506 (8-15 ng/mL) within 7d, versus >7d. Secondary endpoints included: time within therapeutic range (TTR) at 1M and incidence of acute kidney injury (AKI) within 14d. Results Median time to therapeutic was 7d (IQR 5.0-10.0) in 222 patients. There was no difference in ACR [7.6% vs 9.7% (p=0.63)] or dnDSA [35% vs 44% (p=0.20)] between patients achieving therapeutic FK506 ≤7d vs >7d. Recipients therapeutic ≤7d had a longer median time to dnDSA development (44d vs 27d, p=0.043). TTR at 1M was longer in patients therapeutic ≤7d (40% vs 28%, p Conclusion There was no significant differences in development of ACR or dnDSA within 6M between LTx recipients achieving therapeutic FK506 ≤7d vs >7d. Increased time to dnDSA development in the ≤7d cohort suggests a potential benefit to minimizing time to therapeutic FK506 level post-LTx.