Impact of Tacrolimus Trough Variability on Acute Rejection Following Lung Transplantation

Abstract

Acute rejection is a risk factor for the development of chronic lung allograft dysfunction, the leading cause of morbidity and mortality in lung transplant recipients. Calcineurin inhibitors are the cornerstone of immunosuppression regimens after lung transplantation. We retrospectively evaluated the association of tacrolimus level variability with total acute rejection score at 12 months post-transplant. Secondary outcomes included the development of chronic lung allograft dysfunction and antibody-mediated rejection at 24months post-transplant. There were 229 lung transplant recipients included. The mean (standard deviation) total rejection score of the cohort was 1.6 (1.7). Patients with high tacrolimus variability at 0 to 3, 3 to 6, and 6 to 12 months on average scored 0.18 (mean 1.6 vs 1.5; 95% CI): -0.3 to 0.66, P=.46), 0.14 (mean 1.7 vs 1.5; 95% CI: -0.32 to 0.6, P=.55), and 0.12 (mean 1.6 vs 1.5; 95% CI: -0.34 to 0.58, P=.62) point higher in 12-month total acute rejection scores, respectively; however, these differences were not statistically significant. The incidences of chronic lung allograft dysfunction and antibody-mediated rejection were numerically greater in the high variability group throughout certain periods; however, this was not consistent throughout all study timeframes and statistical significance was not evaluated. High tacrolimus variability was not associated with increased 12-month total acute rejection score. Further studies are needed to assess long-term outcomes with tacrolimus level variability.