Walters Samuel, Yerkovich Stephanie, Hopkins Peter M, Leisfield Trish, Winks Lesleigh, Chambers Daniel C, Divithotawela Chandima
University of Queensland, Brisbane, Australia.
Queensland Lung Transplant Service, The Prince Charles Hospital, Brisbane, Australia.
JHLT Open. 2023 Dec 13;3:100043. doi: 10.1016/j.jhlto.2023.100043. eCollection 2024 Feb.
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.
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.
Tacrolimus CoV from 6 to 12 months was independently associated with both CLAD (hazard ratio [HR], 19.99; 95% CI, 7.55-52.91; < 0.001) and death (HR, 14.57; 95% (confidence interval) CI, 6.08-34.90; < 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; = 0.34) or death (HR, 0.91; 95% CI, 0.82-1.01; = 0.07). In a multivariable model, erratic tacrolimus levels were associated with antifungal use (β 0.10 95% CI 0.54-1.51, < 0.001) and younger age (Î -0.0015, 95% CI -0.17 to -0.03, = 0.005 per 5 years).
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.
此前已有描述称，他克莫司血药浓度不稳定与肾移植和肝移植中的移植物功能衰竭有关。我们之前使用一个小队列研究发现，肺移植后6至12个月他克莫司的标准差（SD）较高会增加慢性肺移植功能障碍（CLAD）和死亡的风险。我们旨在使用变异系数（CoV）在更大的队列中评估这一情况，并确定CoV升高的潜在风险因素。
我们回顾性分析了351例接受基于他克莫司的免疫抑制治疗的肺移植受者。采用Cox比例风险模型研究他克莫司平均水平和CoV对生存及CLAD的影响。
6至12个月的他克莫司CoV与CLAD（风险比[HR]，19.99；95%置信区间[CI]，7.55 - 52.91；P < 0.001）和死亡（HR，14.57；95% CI，6.08 - 34.90；P < 0.001）均独立相关。相反，6至12个月期间他克莫司的平均谷血药浓度与CLAD风险增加无关（HR，0.94；95% CI，0.
