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ORIGINAL RESEARCH article

Front. Nutr.

Sec. Clinical Nutrition

Volume 12 - 2025 | doi: 10.3389/fnut.2025.1679774

Comprehensive Dietary Antioxidant Index and Chronic Kidney Disease: Mediating Role of Frailty and Its Impact on Mortality Outcomes in Adults

Provisionally accepted
Wenqing  LiWenqing Li1Shuang  ChenShuang Chen2Jiangmin  WanJiangmin Wan3Liyuan  ChenLiyuan Chen1Lingzhi  XingLingzhi Xing1Zhenglan  GaoZhenglan Gao3*Ling  ChenLing Chen1*
  • 1Chongqing Medical University, Chongqing, China
  • 2Sichuan Tianfu New District People's Hospital, Chengdu, China
  • 3Chongqing Hospital of Jiangsu Province Hospital, chongqing, China

The final, formatted version of the article will be published soon.

Background Chronic kidney disease (CKD) poses significant global health challenges, with oxidative stress and inflammation contributing to its pathogenesis. While dietary antioxidants may mitigate CKD risk, reflected by Comprehensive Dietary Antioxidant Index (CDAI), the mediating role of frailty (FI) remains underexplored. This study investigates the association between CDAI and CKD risk, with a focus on FI as a potential mediator and its implications for mortality outcomes. Methods Utilizing data from 11904 U.S. adults in the National Health and Nutrition Examination Survey (NHANES, 2011–2018), we analyzed CDAI (comprising manganese, selenium, zinc, and vitamins A, C, E) and its association with CKD. Multivariable logistic regression, restricted cubic splines, and Cox proportional hazards models assessed relationships between CDAI, FI, CKD, and mortality. Mediation analysis quantified FI's role in CDAI-CKD associations. Results Higher CDAI scores were inversely associated with CKD prevalence (OR = 0.802, 95%CI [0.753, 0.854], P < 0.001), with a 46.6% lower CKD risk in the highest vs. lowest CDAI quartile. Frailty mediated 36% (95% CI: 35–38%) of the CDAI-CKD relationship. Manganese and vitamin C exhibited independent protective effects against CKD (P < 0.001). Survival analyses revealed lower CDAI correlated with higher all-cause mortality in pre-frail CKD patients (P = 0.030) and elevated cardiovascular mortality in frail patients (P < 0.0001). Vitamin E inversely linked to cardiovascular mortality (HR = 0.934, P = 0.019), while vitamin A increased risk (HR = 1.266, P = 0.005). Conclusions CDAI is inversely associated with CKD risk, partially mediated by FI. Dietary antioxidant intake, particularly vitamins This is a provisional file, not the final typeset article C and E, may improve outcomes in CKD populations, especially those with frailty. These findings highlight the potential of nutritional interventions to mitigate CKD progression and mortality. Further randomized trials are needed to confirm causality and optimize dietary strategies for high-risk groups.

Keywords: antioxidant, Chronic Kidney Disease, Frailty, Mediation analysis, Mortality

Received: 05 Aug 2025; Accepted: 26 Sep 2025.

Copyright: © 2025 Li, Chen, Wan, Chen, Xing, Gao and Chen. 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:
Zhenglan Gao, 526995528@qq.com
Ling Chen, chenling@cqmu.edu.cn

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