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

<b>Background/Objectives</b>: 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). <b>Methods</b>: In this cross-s...

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Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/17/5/590
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author 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
author_facet 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
author_sort Svea Nolte
collection DOAJ
description <b>Background/Objectives</b>: 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). <b>Methods</b>: 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. <b>Results</b>: 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 (<i>p</i> < 0.001). Both whole blood and plasma concentrations were significantly associated with daily tacrolimus dose (both <i>p</i> < 0.001). Compared to whole blood tacrolimus concentrations, plasma tacrolimus concentration showed a strong negative association with worse HRQoL (PCS: st. β = −0.12, <i>p</i> = 0.01; MCS: st. β = −0.14, <i>p</i> < 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%). <b>Conclusions</b>: 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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spelling doaj-art-06d47f2bab604c7f80ded8e477350c192025-08-20T03:14:32ZengMDPI AGPharmaceutics1999-49232025-04-0117559010.3390/pharmaceutics17050590Plasma Versus Whole Blood Tacrolimus Concentrations and Health-Related Quality of Life in Kidney Transplant RecipientsSvea Nolte0J. Casper Swarte1Tim J. Knobbe2Ilja M. Nolte3Tanja R. Zijp4Harmen R. Moes5Marco van Londen6Niels L. Riemersma7Johannes R. Björk8Rinse K. Weersma9Gea Drost10Stefan P. Berger11Daan J. Touw12Stephan J. L. Bakker13Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDivision of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDivision of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Epidemiology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Neurology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDivision of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDivision of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Neurology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDivision of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDivision of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands<b>Background/Objectives</b>: 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). <b>Methods</b>: 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. <b>Results</b>: 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 (<i>p</i> < 0.001). Both whole blood and plasma concentrations were significantly associated with daily tacrolimus dose (both <i>p</i> < 0.001). Compared to whole blood tacrolimus concentrations, plasma tacrolimus concentration showed a strong negative association with worse HRQoL (PCS: st. β = −0.12, <i>p</i> = 0.01; MCS: st. β = −0.14, <i>p</i> < 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%). <b>Conclusions</b>: 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.https://www.mdpi.com/1999-4923/17/5/590tacrolimuskidney transplant recipientshealth-related quality of lifetherapeutic drug monitoring
spellingShingle 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
Plasma Versus Whole Blood Tacrolimus Concentrations and Health-Related Quality of Life in Kidney Transplant Recipients
Pharmaceutics
tacrolimus
kidney transplant recipients
health-related quality of life
therapeutic drug monitoring
title Plasma Versus Whole Blood Tacrolimus Concentrations and Health-Related Quality of Life in Kidney Transplant Recipients
title_full Plasma Versus Whole Blood Tacrolimus Concentrations and Health-Related Quality of Life in Kidney Transplant Recipients
title_fullStr Plasma Versus Whole Blood Tacrolimus Concentrations and Health-Related Quality of Life in Kidney Transplant Recipients
title_full_unstemmed Plasma Versus Whole Blood Tacrolimus Concentrations and Health-Related Quality of Life in Kidney Transplant Recipients
title_short Plasma Versus Whole Blood Tacrolimus Concentrations and Health-Related Quality of Life in Kidney Transplant Recipients
title_sort plasma versus whole blood tacrolimus concentrations and health related quality of life in kidney transplant recipients
topic tacrolimus
kidney transplant recipients
health-related quality of life
therapeutic drug monitoring
url https://www.mdpi.com/1999-4923/17/5/590
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