Low Tacrolimus trough concentration and high intra-patient variability are associated with chronic lung allograft dysfunction and mortality in lung transplantation recipients

Abstract

Abstract Background Erratic tacrolimus (Tac) exposure is associated with poor long-term outcomes after kidney transplantation. However, detailed data on the association in lung transplant recipients are lacking.Aim We hypothesized that Tac intra-patient variability (Tac IPV) or mean concentration was associated with chronic lung allograft dysfunction (CLAD) and survival after lung transplantation.Methods Data from 132 lung transplant recipients were analyzed retrospectively. Tac trough concentration during 0–6, 6–12 and 12–24 months after transplantation were collected. Tac IPV was calculated based on coefficient of variation. Univariate and multivariate COX analyses were performed to identify risk factors for CLAD and survival.Results Of the 132 patients analyzed, 31 (23.5%) developed CLAD and 20 (15.2%) died. Patients received significantly more intensive monitoring of Tac concentration at 0–6 months and Tac IPV was the highest (median: 33.98%) at this period, while after 6 months it lowered to a relatively steady level. A higher mean concentration at 6–12 months [Hazard Ratio (HR) 0.358 (95% CI: 0.137–0.933)] and at 12–24 months [HR 0.351 (95% CI: 0.136–0.904)] was a protective factor for CLAD incidence, while a higher Tac IPV at 6–12 months [HR 2.839 (95% CI: 1.063–7.585)] was associated with increased risk of mortality.Conclusion Our data indicates that Tac mean concentration and IPV had significant impact on CLAD incidence and mortality in lung transplant recipients. Routine monitoring of Tac concentration and IPV may help identify in patients at increased risk for inferior long-term outcomes.