Precision Monitoring of Immunosuppressive Agent Concentrations in Cardiac Tissue of Pediatric Heart Transplant Recipients

Hashimoto, Kazuhisa; Kimura, Natsuka; Narita, Jun; Ishii, Ryo; Hirose, Masaki; Hayashi, Ken; Nishino, Haruka; Ueyama, Atsuko; Ueda, Kazutoshi; Yoshihara, Chika; Kitabatake, Yasuji; Nagai, Ryozo; Aizawa, Kenichi; Ishida, Hidekazu

doi:https://doi.org/10.1111/petr.70092

Precision Monitoring of Immunosuppressive Agent Concentrations in Cardiac Tissue of Pediatric Heart Transplant Recipients

Hashimoto, Kazuhisa; Kimura, Natsuka; Narita, Jun et al.

Pediatric Transplantation, 2025, 29(4), e70092

Number of Access:2（2025-07-22 20:34 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/102224

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Title	Precision Monitoring of Immunosuppressive Agent Concentrations in Cardiac Tissue of Pediatric Heart Transplant Recipients
Creator	CreatorName Hashimoto, Kazuhisa
	NRID 1000090884453 1000090884453 CreatorName Kimura, Natsuka
	NRID 1000070467562 1000070467562 researchmap permalink J-narita J-narita Scopus Author ID 36993204400 36993204400 CreatorName Narita, Jun
	NRID 1000090794008 1000090794008 researchmap permalink iryo-0918 iryo-0918 Scopus Author ID 56017974100 56017974100 CreatorName Ishii, Ryo
	CreatorName Hirose, Masaki
	CreatorName Hayashi, Ken
	CreatorName Nishino, Haruka
	CreatorName Ueyama, Atsuko
	CreatorName Ueda, Kazutoshi
	CreatorName Yoshihara, Chika
	NRID 1000080506494 1000080506494 ORCID 0000-0002-2907-9512 0000-0002-2907-9512 researchmap permalink kyasuji kyasuji Scopus Author ID 7003894272 7003894272 CreatorName Kitabatake, Yasuji
	NRID 1000060207975 1000060207975 CreatorName Nagai, Ryozo
	NRID 1000070436484 1000070436484 CreatorName Aizawa, Kenichi
	NRID 1000050467552 1000050467552 researchmap permalink researcher_cardio researcher_cardio Scopus Author ID 36863872000 36863872000 CreatorName Ishida, Hidekazu
Subject	heart transplantation
	immunosuppressive treatment
	liquid chromatography–tandem mass spectrometry
	therapeutic drug monitoring
Description	Hashimoto K., Kimura N., Narita J., et al. Precision Monitoring of Immunosuppressive Agent Concentrations in Cardiac Tissue of Pediatric Heart Transplant Recipients. Pediatric Transplantation 29 (4), e70092 (2025); https://doi.org/10.1111/petr.70092.
Abstract	Background: Management of immunosuppressive therapy after heart transplantation is typically guided by blood trough levels. Although tissue concentrations of immunosuppressive agents reportedly correlate with acute rejection in liver and kidney allografts, data in pediatric heart transplant recipients remain limited. Methods: We enrolled 41 pediatric heart transplant recipients who underwent follow-up endomyocardial biopsy (EMB) between July 2021 and December 2023. For nine of those patients, serial data were collected up to 24 weeks post-transplantation. Myocardial tissue concentrations of tacrolimus (TAC), everolimus (EVR), mycophenolic acid (MPA), and mycophenolic acid glucuronide (MPAG) were measured by liquid chromatography–tandem mass spectrometry (LC–MS/MS), while blood concentrations were quantified by LC–MS/MS or immunoassays. Results: Significant correlations were observed between myocardial and blood concentrations at EMB for TAC (r = 0.73, p < 0.0001), MPA (r = 0.79, p < 0.0001), and MPAG (r = 0.50, p < 0.0001). However, for EVR there was no significant correlation. Longitudinal analysis demonstrated that the tissue-to-blood TAC and EVR ratios decreased with age. No significant rejection events were observed during the study period, precluding the analysis of rejection risk. Conclusion: Myocardial TAC, MPA, and MPAG concentrations are associated with blood levels, whereas those of EVR showed no significant correlation. Further, the tissue perfusion efficiencies of TAC and EVR decreased with age. This study highlights the value of LC–MS/MS for immunosuppressant monitoring after pediatric heart transplantation.
Publisher	John Wiley and Sons Inc
Source Title	Pediatric Transplantation
Volume (Issue)	29(4)
Page	e70092
Date of Issued	2025-04-28
Language	English
Handle URL	https://hdl.handle.net/11094/102224
PISSN	13973142
eISSN	13993046
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1111/petr.70092
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Pediatric Transplantation. 2025, 29(4), p. e70092
DC.title	Precision Monitoring of Immunosuppressive Agent Concentrations in Cardiac Tissue of Pediatric Heart Transplant Recipients
DC.creator	Hashimoto, Kazuhisa
	Kimura, Natsuka
	Narita, Jun
	Ishii, Ryo
	Hirose, Masaki
	Hayashi, Ken
	Nishino, Haruka
	Ueyama, Atsuko
	Ueda, Kazutoshi
	Yoshihara, Chika
	Kitabatake, Yasuji
	Nagai, Ryozo
	Aizawa, Kenichi
	Ishida, Hidekazu
DC.publisher	John Wiley and Sons Inc
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-04-28
DC.identifier	https://doi.org/10.1111/petr.70092
DC.subject	heart transplantation
	immunosuppressive treatment
	liquid chromatography–tandem mass spectrometry
	therapeutic drug monitoring
DC.description	Hashimoto K., Kimura N., Narita J., et al. Precision Monitoring of Immunosuppressive Agent Concentrations in Cardiac Tissue of Pediatric Heart Transplant Recipients. Pediatric Transplantation 29 (4), e70092 (2025); https://doi.org/10.1111/petr.70092.
DCTERMS.abstract	Background: Management of immunosuppressive therapy after heart transplantation is typically guided by blood trough levels. Although tissue concentrations of immunosuppressive agents reportedly correlate with acute rejection in liver and kidney allografts, data in pediatric heart transplant recipients remain limited. Methods: We enrolled 41 pediatric heart transplant recipients who underwent follow-up endomyocardial biopsy (EMB) between July 2021 and December 2023. For nine of those patients, serial data were collected up to 24 weeks post-transplantation. Myocardial tissue concentrations of tacrolimus (TAC), everolimus (EVR), mycophenolic acid (MPA), and mycophenolic acid glucuronide (MPAG) were measured by liquid chromatography–tandem mass spectrometry (LC–MS/MS), while blood concentrations were quantified by LC–MS/MS or immunoassays. Results: Significant correlations were observed between myocardial and blood concentrations at EMB for TAC (r = 0.73, p < 0.0001), MPA (r = 0.79, p < 0.0001), and MPAG (r = 0.50, p < 0.0001). However, for EVR there was no significant correlation. Longitudinal analysis demonstrated that the tissue-to-blood TAC and EVR ratios decreased with age. No significant rejection events were observed during the study period, precluding the analysis of rejection risk. Conclusion: Myocardial TAC, MPA, and MPAG concentrations are associated with blood levels, whereas those of EVR showed no significant correlation. Further, the tissue perfusion efficiencies of TAC and EVR decreased with age. This study highlights the value of LC–MS/MS for immunosuppressant monitoring after pediatric heart transplantation.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
DC.format	102224
citation_title	Precision Monitoring of Immunosuppressive Agent Concentrations in Cardiac Tissue of Pediatric Heart Transplant Recipients
citation_author	Hashimoto, Kazuhisa
	Kimura, Natsuka
	Narita, Jun
	Ishii, Ryo
	Hirose, Masaki
	Hayashi, Ken
	Nishino, Haruka
	Ueyama, Atsuko
	Ueda, Kazutoshi
	Yoshihara, Chika
	Kitabatake, Yasuji
	Nagai, Ryozo
	Aizawa, Kenichi
	Ishida, Hidekazu
citation_publisher	John Wiley and Sons Inc
citation_language	English
citation_date	2025-04-28
citation_journal_title	Pediatric Transplantation
citation_volume	29
citation_issue	4
citation_firstpage	e70092
citation_doi	https://doi.org/10.1111/petr.70092
citation_public_url	https://hdl.handle.net/11094/102224

Precision Monitoring of Immunosuppressive Agent Concentrations in Cardiac Tissue of Pediatric Heart Transplant Recipients

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