ORIGINAL RESEARCH article
Front. Med.
Sec. Nephrology
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1636392
This article is part of the Research TopicThe Cardiovascular Continuum Between Hypertension, Diabetes and Cardiovascular DiseaseView all 9 articles
Intensive Glycemic Control and Kidney Disease Risk: Insights on Hierarchical Composite Endpoint from a Randomized Clinical Trial
Provisionally accepted
- 1Xi'an Jiaotong University Health Science Center, Xian, China
- 2Xi'an Jiaotong University School of Economics and Finance, XiAn, China
- 3Shaannxi International Trust Limited-liability Company, Xi'an, China
- 4Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an, China
- 5Liverpool School of Tropical Medicine Department of Clinical Sciences, Liverpool, United Kingdom
- 6Baoji Central Hospital Infectious Disease Department, Baoji, China
- 7Shaanxi Provincial Center for Disease Control and Prevention, Xi'an, China
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Background Clinical trials of intensive glycemic control in patients with type 2 diabetes mellitus (T2DM) and high cardiovascular risk have reported inconsistent findings regarding chronic kidney disease (CKD) outcomes, partly due to heterogeneity in event definitions and reliance on conventional time-to-first-event analysis. This study aimed to evaluate the renal effects of intensive glycemic control using a hierarchical composite endpoint (HCE) ranked by clinical severity and analyzed via the Win Odds (WO) method Method This post-hoc analysis included patients from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) glycemia trial. We employed the win ratio statistical method to estimate the treatment effects on HCE, defined as a ranked composite of all-cause mortality, kidney failure, sustained estimated glomerular filtration rate (eGFR) declines of 57%, 50%, and 40% from baseline, persistent eGFR <15 mL/min/1.73 m 2 , and eGFR slope. The effects of intensive glycemic control on individual HCE components and various composite kidney endpoints was assessed by Cox regression models.Among the 9,848 participants, sustained 40% eGFR decline was the most frequent renal event in the hierarchical composite. Intensive glucose control was not associated with a significant difference in the HCE compared to standard therapy (WO = 1.03, 95% CI: 0.99-1.07). This finding was consistent with results from Cox regression (HR = 1.05, 95% CI: 0.97 -1.13) and across individual components of the composite endpoint.In individuals with T2DM at high risk for cardiovascular disease, intensive glycemic control does not demonstrate a significantly detrimental effect on hierarchical composite kidney outcomes.
Keywords: Type 2 diabetes mellitus1, Intensive glycemic control2, diabetic kidney disease3, Hierarchical composite endpoint4, Cardiovascular Risk5, Cardio-renal syndrome6, Win Odds7
Received: 29 May 2025; Accepted: 29 Jul 2025.
Copyright: © 2025 Song, Xu, Zhang, Liu, Li, Chen, Guo and Zhu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ni Zhu, Shaanxi Provincial Center for Disease Control and Prevention, Xi'an, China
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