Nolte Svea, Swarte J Casper, Knobbe Tim J, Nolte Ilja M, Zijp Tanja R, Moes Harmen R, van Londen Marco, Riemersma Niels L, Björk Johannes R, Weersma Rinse K, Drost Gea, Berger Stefan P, Touw Daan J, Bakker Stephan J L
Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.
Department of Neurology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.
Pharmaceutics. 2025 Apr 30;17(5):590. doi: 10.3390/pharmaceutics17050590.
: Tacrolimus dosing traditionally relies on therapeutic drug monitoring in whole blood, while assessment in plasma may better reflect its effect and reveal overdosing impacting health-related quality of life (HRQoL). : In this cross-sectional study, 898 kidney transplant recipients (KTRs) who were at least 12 months post-transplantation were included. Plasma and whole blood tacrolimus concentrations were compared using Passing-Bablok regression analyses and Bland-Altman plots. Furthermore, the relationship with daily tacrolimus dose and with HRQoL (mental component summary (MCS), physical component summary (PCS)) was explored using linear regression by comparing standardized coefficients. Lastly, mediation analyses explored the effect of various tacrolimus-related side effects on the association between tacrolimus concentrations and HRQoL. : Comparison of the methods revealed a constant bias and a slight proportional bias between whole blood and plasma tacrolimus concentrations. The Bland-Altman plots indicated poor agreement with a statistically significant ratio difference ( < 0.001). Both whole blood and plasma concentrations were significantly associated with daily tacrolimus dose (both < 0.001). Compared to whole blood tacrolimus concentrations, plasma tacrolimus concentration showed a strong negative association with worse HRQoL (PCS: st. β = -0.12, = 0.01; MCS: st. β = -0.14, < 0.001). The associations between plasma tacrolimus concentrations and HRQoL were mediated by fatigue severity (proportion mediated on PCS: 67.8%, MCS: 59.5%) and reduced kidney function (proportion mediated on PCS: 16.7%, MCS: 12.9%). : In conclusion, compared with whole blood tacrolimus concentrations, plasma tacrolimus concentrations exhibited a negative association with HRQoL in KTRs. Consequently, therapeutic drug monitoring using plasma tacrolimus concentrations may reduce the occurrence of tacrolimus-related toxicity.
传统上，他克莫司的给药依赖于全血中的治疗药物监测，而血浆中的评估可能能更好地反映其效果，并揭示影响健康相关生活质量（HRQoL）的用药过量情况。在这项横断面研究中，纳入了898名移植后至少12个月的肾移植受者（KTRs）。使用Passing-Bablok回归分析和Bland-Altman图比较血浆和全血他克莫司浓度。此外，通过比较标准化系数，使用线性回归探索与每日他克莫司剂量以及与HRQoL（心理成分总结（MCS）、身体成分总结（PCS））的关系。最后，中介分析探讨了各种他克莫司相关副作用对他克莫司浓度与HRQoL之间关联的影响。方法比较显示全血和血浆他克莫司浓度之间存在恒定偏差和轻微的比例偏差。Bland-Altman图表明一致性较差，比率差异具有统计学意义（<0.001）。全血和血浆浓度均与每日他克莫司剂量显著相关（均<0.001）。与全血他克莫司浓度相比，血浆他克莫司浓度与较差的HRQoL呈强负相关（PCS：标准β=-0.12，P=0.01；MCS：标准β=-0.14，P<0.001）。血浆他克莫司浓度与HRQoL之间的关联由疲劳严重程度（PCS中介比例：67.8%，MCS中介比例：59.5%）和肾功能下降（PCS中介比例：16.7%，MCS中介比例：12.9%）介导。总之，与全血他克莫司浓度相比，血浆他克莫司浓度在KTRs中与HRQoL呈负相关。因此，使用血浆他克莫司浓度进行治疗药物监测可能会减少他克莫司相关毒性的发生。
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