Mediators between canagliflozin and renoprotection vary depending on patient characteristics: Insights from the CREDENCE trial

Doi, Yohei; Hamano, Takayuki; Yamaguchi, Satoshi; Sakaguchi, Yusuke22739544; Kaimori, Jun-Ya; Isaka, Yoshitaka

doi:https://doi.org/10.1111/dom.15191

Mediators between canagliflozin and renoprotection vary depending on patient characteristics: Insights from the CREDENCE trial

Doi, Yohei; Hamano, Takayuki; Yamaguchi, Satoshi et al.

Diabetes, Obesity and Metabolism, 2023, 25(10), 2944-2953

アクセス数:1,128件（2025-09-12 08:47 集計）

固定URL: https://hdl.handle.net/11094/92480

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タイトル	Mediators between canagliflozin and renoprotection vary depending on patient characteristics: Insights from the CREDENCE trial
著者	NRID 1000030846382 1000030846382 ORCID 0000-0002-5165-291X 0000-0002-5165-291X researchmap permalink DOI-YOHEI DOI-YOHEI 著者名 Doi, Yohei
	著者名 Hamano, Takayuki
	著者名 Yamaguchi, Satoshi
	NRID 1000080756817 1000080756817 researchmap permalink sakaguchi-handai3857 sakaguchi-handai3857 Scopus Author ID 35183980700 35183980700 ORCID 0000-0002-0987-5423 0000-0002-0987-5423 著者名 Sakaguchi, Yusuke22739544
	NRID 1000070527697 1000070527697 著者名 Kaimori, Jun-Ya
	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
キーワード等	canagliflozin
	clinical trial
	diabetic nephropathy
	drug mechanism
	type 2 diabetes
内容	Doi Y., Hamano T., Yamaguchi S., et al. Mediators between canagliflozin and renoprotection vary depending on patient characteristics: Insights from the CREDENCE trial. Diabetes, Obesity and Metabolism , (2023); https://doi.org/10.1111/dom.15191.
抄録	Aim: To identify the mediators between canagliflozin and renoprotection in patients with type 2 diabetes at a high risk of end-stage kidney disease (ESKD). Methods: In this post hoc analysis of the CREDENCE trial, the effect of canagliflozin on potential mediators (42 biomarkers) at 52 weeks and the association between changes in mediators and renal outcomes were evaluated using mixed-effects and Cox models, respectively. The renal outcome was a composite of ESKD, serum creatinine doubling or renal death. The percentage of the mediating effect of each significant mediator was calculated based on changes in the hazard ratios of canagliflozin after additional adjustment of the mediator. Results: Changes in haematocrit, haemoglobin, red blood cell (RBC) count and urinary albumin-to-creatinine ratio (UACR) at 52 weeks significantly mediated 47%, 41%, 40% and 29% risk reduction with canagliflozin, respectively. Further, 85% mediation was attributed to the combined effect of haematocrit and UACR. A large variation in mediating effects by haematocrit change existed among the subgroups, ranging from 17% in those patients with a UACR of more than 3000 mg/g to 63% in patients with a UACR of 3000 mg/g or less. In the subgroups with a UACR of more than 3000 mg/g, UACR change was the highest mediating factor (37%), driven by the strong association between UACR decline and renal risk reduction. Conclusions: The renoprotective effects of canagliflozin in patients at a high risk of ESKD can be significantly explained by changes in RBC variables and UACR. The complementary mediating effects of RBC variables and UACR may support the renoprotective effect of canagliflozin in different patient groups.
出版者	John Wiley and Sons Inc
収録物名	Diabetes, Obesity and Metabolism
巻(号)	25(10)
ページ	2944-2953
刊行年月	2023-01-29
言語	英語
ハンドルURL	https://hdl.handle.net/11094/92480
PISSN	14628902
eISSN	14631326
NCID	AA11621016
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1111/dom.15191
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
DCMI資源タイプ	text
DCTERMS.bibliographicCitation	Diabetes, Obesity and Metabolism. 2023, 25(10), p. 2944-2953
DC.title	Mediators between canagliflozin and renoprotection vary depending on patient characteristics: Insights from the CREDENCE trial
DC.creator	Doi, Yohei
	Hamano, Takayuki
	Yamaguchi, Satoshi
	Sakaguchi, Yusuke22739544
	Kaimori, Jun-Ya
	Isaka, Yoshitaka
DC.publisher	John Wiley and Sons Inc
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2023-01-29
DC.identifier	https://doi.org/10.1111/dom.15191
DC.subject	canagliflozin
	clinical trial
	diabetic nephropathy
	drug mechanism
	type 2 diabetes
DC.description	Doi Y., Hamano T., Yamaguchi S., et al. Mediators between canagliflozin and renoprotection vary depending on patient characteristics: Insights from the CREDENCE trial. Diabetes, Obesity and Metabolism , (2023); https://doi.org/10.1111/dom.15191.
DCTERMS.abstract	Aim: To identify the mediators between canagliflozin and renoprotection in patients with type 2 diabetes at a high risk of end-stage kidney disease (ESKD). Methods: In this post hoc analysis of the CREDENCE trial, the effect of canagliflozin on potential mediators (42 biomarkers) at 52 weeks and the association between changes in mediators and renal outcomes were evaluated using mixed-effects and Cox models, respectively. The renal outcome was a composite of ESKD, serum creatinine doubling or renal death. The percentage of the mediating effect of each significant mediator was calculated based on changes in the hazard ratios of canagliflozin after additional adjustment of the mediator. Results: Changes in haematocrit, haemoglobin, red blood cell (RBC) count and urinary albumin-to-creatinine ratio (UACR) at 52 weeks significantly mediated 47%, 41%, 40% and 29% risk reduction with canagliflozin, respectively. Further, 85% mediation was attributed to the combined effect of haematocrit and UACR. A large variation in mediating effects by haematocrit change existed among the subgroups, ranging from 17% in those patients with a UACR of more than 3000 mg/g to 63% in patients with a UACR of 3000 mg/g or less. In the subgroups with a UACR of more than 3000 mg/g, UACR change was the highest mediating factor (37%), driven by the strong association between UACR decline and renal risk reduction. Conclusions: The renoprotective effects of canagliflozin in patients at a high risk of ESKD can be significantly explained by changes in RBC variables and UACR. The complementary mediating effects of RBC variables and UACR may support the renoprotective effect of canagliflozin in different patient groups.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
DC.format	92480
citation_title	Mediators between canagliflozin and renoprotection vary depending on patient characteristics: Insights from the CREDENCE trial
citation_author	Doi, Yohei
	Hamano, Takayuki
	Yamaguchi, Satoshi
	Sakaguchi, Yusuke22739544
	Kaimori, Jun-Ya
	Isaka, Yoshitaka
citation_publisher	John Wiley and Sons Inc
citation_language	英語
citation_date	2023-01-29
citation_journal_title	Diabetes, Obesity and Metabolism
citation_volume	25
citation_issue	10
citation_firstpage	2944
citation_lastpage	2953
citation_doi	https://doi.org/10.1111/dom.15191
citation_public_url	https://hdl.handle.net/11094/92480

Mediators between canagliflozin and renoprotection vary depending on patient characteristics: Insights from the CREDENCE trial

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