Impact of Immunosuppressive Drug Concentrations on Microvascular Inflammation, Negative Donor‐Specific Antibodies, and C4d‐Negative Status in Kidney Transplant Recipients

Kakuta, Yoichi; Maegawa-Higa, Yoko; Matsumura, Soichi; Fukae, Shota; Tanaka, Ryo; Yonishi, Hiroaki; Nakazawa, Shigeaki; Namba‐Hamano, Tomoko; Isaka, Yoshitaka; Nonomura, Norio

doi:https://doi.org/10.1111/ctr.70112

Impact of Immunosuppressive Drug Concentrations on Microvascular Inflammation, Negative Donor‐Specific Antibodies, and C4d‐Negative Status in Kidney Transplant Recipients

Kakuta, Yoichi; Maegawa-Higa, Yoko; Matsumura, Soichi et al.

Clinical Transplantation, 2025, 39(2), e70112

アクセス数:1,491件（2025-08-15 06:48 集計）

固定URL: https://hdl.handle.net/11094/100550

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タイトル	Impact of Immunosuppressive Drug Concentrations on Microvascular Inflammation, Negative Donor‐Specific Antibodies, and C4d‐Negative Status in Kidney Transplant Recipients
著者	NRID 1000040710116 1000040710116 researchmap permalink 987654321 987654321 ORCID 0000-0001-5339-4312 0000-0001-5339-4312 著者名 Kakuta, Yoichi
	著者名 Maegawa-Higa, Yoko
	NRID 1000090981986 1000090981986 著者名 Matsumura, Soichi
	NRID 1000000964397 1000000964397 著者名 Fukae, Shota
	NRID 1000060909654 1000060909654 ORCID 0000-0003-1144-7820 0000-0003-1144-7820 researchmap permalink ryotnk0302 ryotnk0302 著者名 Tanaka, Ryo
	NRID 1000040822143 1000040822143 著者名 Yonishi, Hiroaki
	NRID 1000080759530 1000080759530 ORCID 0000-0001-5857-3483 0000-0001-5857-3483 researchmap permalink snakazawa snakazawa Scopus Author ID 36350232600 36350232600 著者名 Nakazawa, Shigeaki
	NRID 1000030734420 1000030734420 researchmap permalink namba-handai3857 namba-handai3857 Scopus Author ID 8577526800 8577526800 著者名 Namba‐Hamano, Tomoko
	NRID 1000000379166 1000000379166 researchmap permalink isaka-handai3857 isaka-handai3857 Scopus Author ID 16207611100 16207611100 ORCID 0000-0002-0820-7167 0000-0002-0820-7167 著者名 Isaka, Yoshitaka
	NRID 1000030263263 1000030263263 researchmap permalink read0185096 read0185096 Scopus Author ID 7005880662 7005880662 著者名 Nonomura, Norio
キーワード等	C4d
	donor-specific antibodies
	graft rejection
	immunosuppressive drugs
	kidney transplantation
	microvascular inflammation
	transplant immunology
内容	Kakuta Yoichi, Maegawa‐Higa Yoko, Matsumura Soichi, et al. Impact of Immunosuppressive Drug Concentrations on Microvascular Inflammation, Negative Donor‐Specific Antibodies, and C4d‐Negative Status in Kidney Transplant Recipients. Clinical Transplantation 39, e70112 (2025); https://doi.org/10.1111/ctr.70112.
抄録	Introduction: This study investigated the impact of immunosuppressive drug concentrations on microvascular inflammation (MVI) in kidney transplant recipients with negative donor-specific antibodies (DSA) against human leukocyte antigen (HLA) and negative C4d deposition in peritubular capillaries. Methods: We analyzed data from 268 living kidney transplant recipients at the Department of Urology, University of Osaka, Japan. Patients received immunosuppressive therapy comprising extended-release tacrolimus, mycophenolate mofetil (MMF), and/or everolimus, with or without steroids. Graft biopsies were routinely performed at 3, 12, 36 and 60 months post-surgery. Results: No significant differences were observed between the MVI+DSA-C4d- and MVI-DSAC4d groups regarding graft survival rates (95.5% vs. 96.6%, p = 0.772) or patient survival rates (95.7% vs. 95.9%, p = 0.735). Lower tacrolimus and everolimus concentrations were significantly associated with an increased risk of MVI+DSA-C4d- (tacrolimus: OR, 0.169; 95% CI, 0.055–0.515; p = 0.002; everolimus: OR, 0.386; 95% CI, 0.171–0.874; p = 0.022). In contrast, MPA concentration was not significantly associated with MVI+DSA-C4d- (OR, 0.994; 95% CI, 0.554–1.780; p = 0.984). Steroid discontinuation did not significantly impact the risk of MVI+DSA-C4d- (OR, 1.980; 95% CI, 0.318–12.000; p = 0.470). Conclusion: Lower trough levels of tacrolimus and everolimus correlated with a higher incidence of antibody-independent MVI, supporting the need for tailored immunosuppressive regimens in kidney transplantation.
出版者	Wiley
収録物名	Clinical Transplantation
巻(号)	39(2)
ページ	e70112
刊行年月	2025-02-21
言語	英語
ハンドルURL	https://hdl.handle.net/11094/100550
PISSN	09020063
eISSN	13990012
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1111/ctr.70112
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCTERMS.bibliographicCitation	Clinical Transplantation. 2025, 39(2), p. e70112
DC.title	Impact of Immunosuppressive Drug Concentrations on Microvascular Inflammation, Negative Donor‐Specific Antibodies, and C4d‐Negative Status in Kidney Transplant Recipients
DC.creator	Kakuta, Yoichi
	Maegawa-Higa, Yoko
	Matsumura, Soichi
	Fukae, Shota
	Tanaka, Ryo
	Yonishi, Hiroaki
	Nakazawa, Shigeaki
	Namba‐Hamano, Tomoko
	Isaka, Yoshitaka
	Nonomura, Norio
DC.publisher	Wiley
DC.language' scheme='DCTERMS.RFC1766	英語
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-02-21
DC.identifier	https://doi.org/10.1111/ctr.70112
DC.subject	C4d
	donor-specific antibodies
	graft rejection
	immunosuppressive drugs
	kidney transplantation
	microvascular inflammation
	transplant immunology
DC.description	Kakuta Yoichi, Maegawa‐Higa Yoko, Matsumura Soichi, et al. Impact of Immunosuppressive Drug Concentrations on Microvascular Inflammation, Negative Donor‐Specific Antibodies, and C4d‐Negative Status in Kidney Transplant Recipients. Clinical Transplantation 39, e70112 (2025); https://doi.org/10.1111/ctr.70112.
DCTERMS.abstract	Introduction: This study investigated the impact of immunosuppressive drug concentrations on microvascular inflammation (MVI) in kidney transplant recipients with negative donor-specific antibodies (DSA) against human leukocyte antigen (HLA) and negative C4d deposition in peritubular capillaries. Methods: We analyzed data from 268 living kidney transplant recipients at the Department of Urology, University of Osaka, Japan. Patients received immunosuppressive therapy comprising extended-release tacrolimus, mycophenolate mofetil (MMF), and/or everolimus, with or without steroids. Graft biopsies were routinely performed at 3, 12, 36 and 60 months post-surgery. Results: No significant differences were observed between the MVI+DSA-C4d- and MVI-DSAC4d groups regarding graft survival rates (95.5% vs. 96.6%, p = 0.772) or patient survival rates (95.7% vs. 95.9%, p = 0.735). Lower tacrolimus and everolimus concentrations were significantly associated with an increased risk of MVI+DSA-C4d- (tacrolimus: OR, 0.169; 95% CI, 0.055–0.515; p = 0.002; everolimus: OR, 0.386; 95% CI, 0.171–0.874; p = 0.022). In contrast, MPA concentration was not significantly associated with MVI+DSA-C4d- (OR, 0.994; 95% CI, 0.554–1.780; p = 0.984). Steroid discontinuation did not significantly impact the risk of MVI+DSA-C4d- (OR, 1.980; 95% CI, 0.318–12.000; p = 0.470). Conclusion: Lower trough levels of tacrolimus and everolimus correlated with a higher incidence of antibody-independent MVI, supporting the need for tailored immunosuppressive regimens in kidney transplantation.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
DC.format	100550
citation_title	Impact of Immunosuppressive Drug Concentrations on Microvascular Inflammation, Negative Donor‐Specific Antibodies, and C4d‐Negative Status in Kidney Transplant Recipients
citation_author	Kakuta, Yoichi
	Maegawa-Higa, Yoko
	Matsumura, Soichi
	Fukae, Shota
	Tanaka, Ryo
	Yonishi, Hiroaki
	Nakazawa, Shigeaki
	Namba‐Hamano, Tomoko
	Isaka, Yoshitaka
	Nonomura, Norio
citation_publisher	Wiley
citation_language	英語
citation_date	2025-02-21
citation_journal_title	Clinical Transplantation
citation_volume	39
citation_issue	2
citation_firstpage	e70112
citation_doi	https://doi.org/10.1111/ctr.70112
citation_public_url	https://hdl.handle.net/11094/100550

Impact of Immunosuppressive Drug Concentrations on Microvascular Inflammation, Negative Donor‐Specific Antibodies, and C4d‐Negative Status in Kidney Transplant Recipients

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