Plasma Versus Whole Blood Tacrolimus Concentrations and Health-Related Quality of Life in Kidney Transplant Recipients.

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Pharmaceutics Pub Date : 2025-04-30 DOI:10.3390/pharmaceutics17050590

Svea Nolte, J Casper Swarte, Tim J Knobbe, Ilja M Nolte, Tanja R Zijp, Harmen R Moes, Marco van Londen, Niels L Riemersma, Johannes R Björk, Rinse K Weersma, Gea Drost, Stefan P Berger, Daan J Touw, Stephan J L Bakker

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引用次数: 0

Abstract

Background/Objectives: 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). Methods: 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. Results: 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 (p < 0.001). Both whole blood and plasma concentrations were significantly associated with daily tacrolimus dose (both p < 0.001). Compared to whole blood tacrolimus concentrations, plasma tacrolimus concentration showed a strong negative association with worse HRQoL (PCS: st. β = -0.12, p = 0.01; MCS: st. β = -0.14, p < 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%). Conclusions: 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.

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肾移植受者血浆与全血他克莫司浓度与健康相关生活质量的关系

背景/目的：他克莫司的给药传统上依赖于全血治疗药物监测，而血浆评估可能更好地反映其效果，揭示过量用药对健康相关生活质量（HRQoL）的影响。方法：在这项横断面研究中，纳入了898例移植后至少12个月的肾移植受者（KTRs）。采用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，通过标准化系数的比较，采用线性回归方法探讨他克莫司日剂量与HRQoL（精神成分总结（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之间关系的影响。结果：两种方法的比较显示全血和血浆他克莫司浓度存在恒定偏倚和轻微的比例偏倚。Bland-Altman图显示与统计学上显著的比值差异不一致（p < 0.001）。全血和血浆浓度均与他克莫司日剂量显著相关（p < 0.001）。与全血他克莫司浓度相比，血浆他克莫司浓度与HRQoL较差呈较强的负相关(PCS: st. β = -0.12, p = 0.01；MCS: st. β = -0.14, p < 0.001)。血浆他克莫司浓度与HRQoL之间的相关性由疲劳程度（PCS组介导比例为67.8%，MCS组为59.5%）和肾功能降低（PCS组介导比例为16.7%，MCS组为12.9%）介导。结论：与全血他克莫司浓度相比，ktr患者血浆他克莫司浓度与HRQoL呈负相关。因此，使用血浆他克莫司浓度进行治疗性药物监测可以减少他克莫司相关毒性的发生。

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来源期刊

Pharmaceutics Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science

CiteScore

7.90

自引率

11.10%

发文量

2379

审稿时长

16.41 days

期刊介绍： Pharmaceutics (ISSN 1999-4923) is an open access journal which provides an advanced forum for the science and technology of pharmaceutics and biopharmaceutics. It publishes reviews, regular research papers, communications, and short notes. Covered topics include pharmacokinetics, toxicokinetics, pharmacodynamics, pharmacogenetics and pharmacogenomics, and pharmaceutical formulation. Our aim is to encourage scientists to publish their experimental and theoretical details in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.