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

Number of Access:1,561（2025-09-12 06:38 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/100550

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Title	Impact of Immunosuppressive Drug Concentrations on Microvascular Inflammation, Negative Donor‐Specific Antibodies, and C4d‐Negative Status in Kidney Transplant Recipients
Creator	NRID 1000040710116 1000040710116 researchmap permalink 987654321 987654321 ORCID 0000-0001-5339-4312 0000-0001-5339-4312 Scopus Author ID 23009020800 23009020800 CreatorName Kakuta, Yoichi
	CreatorName Maegawa-Higa, Yoko
	NRID 1000090981986 1000090981986 CreatorName Matsumura, Soichi
	NRID 1000000964397 1000000964397 CreatorName Fukae, Shota
	NRID 1000060909654 1000060909654 ORCID 0000-0003-1144-7820 0000-0003-1144-7820 researchmap permalink ryotnk0302 ryotnk0302 CreatorName Tanaka, Ryo
	NRID 1000040822143 1000040822143 CreatorName Yonishi, Hiroaki
	NRID 1000080759530 1000080759530 ORCID 0000-0001-5857-3483 0000-0001-5857-3483 researchmap permalink snakazawa snakazawa Scopus Author ID 36350232600 36350232600 CreatorName Nakazawa, Shigeaki
	NRID 1000030734420 1000030734420 researchmap permalink namba-handai3857 namba-handai3857 Scopus Author ID 8577526800 8577526800 CreatorName 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 CreatorName Isaka, Yoshitaka
	NRID 1000030263263 1000030263263 researchmap permalink read0185096 read0185096 Scopus Author ID 7005880662 7005880662 CreatorName Nonomura, Norio
Subject	C4d
	donor-specific antibodies
	graft rejection
	immunosuppressive drugs
	kidney transplantation
	microvascular inflammation
	transplant immunology
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.
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.
Publisher	Wiley
Source Title	Clinical Transplantation
Volume (Issue)	39(2)
Page	e70112
Date of Issued	2025-02-21
Language	English
Handle URL	https://hdl.handle.net/11094/100550
PISSN	09020063
eISSN	13990012
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1111/ctr.70112
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
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	English
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	English
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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