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

Number of Access:1,128（2025-09-12 08:37 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/92480

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Title
Mediators between canagliflozin and renoprotection vary depending on patient characteristics: Insights from the CREDENCE trial
Creator
NRID
1000030846382 1000030846382
ORCID
0000-0002-5165-291X 0000-0002-5165-291X
researchmap permalink
DOI-YOHEI DOI-YOHEI
CreatorName
Doi, Yohei
CreatorName
Hamano, Takayuki
CreatorName
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
CreatorName
Sakaguchi, Yusuke22739544
NRID
1000070527697 1000070527697
CreatorName
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
CreatorName
Isaka, Yoshitaka
Subject
canagliflozin
clinical trial
diabetic nephropathy
drug mechanism
type 2 diabetes
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.
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.
Publisher
John Wiley and Sons Inc
Source Title
Diabetes, Obesity and Metabolism
Volume (Issue)
25(10)
Page
2944-2953
Date of Issued
2023-01-29
Language
English
Handle URL
https://hdl.handle.net/11094/92480
PISSN
14628902
eISSN
14631326
NCID
AA11621016
Relation.isIdenticalTo
DOI (Publisher Version)
https://doi.org/10.1111/dom.15191
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