Relationship between acrylamide and glycidamide hemoglobin adduct levels and chronic kidney disease: A NHANES analysis

IF 6.1 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Ecotoxicology and Environmental Safety Pub Date : 2025-09-17 DOI:10.1016/j.ecoenv.2025.119072

Wen-Tao Xu , Wen-Cai Zheng , Chao-Ran Chen , Fei Lin , Shao-Hao Chen , Xiao-Dong Li , Xiong-Lin Sun , Qing-Shui Zheng , Yong Wei , Xue-Yi Xue , Zhi-Bin Ke , Ning Xu

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引用次数: 0

Abstract

Background

Acrylamide (AA) is a dietary contaminant with experimental nephrotoxicity, yet its relationship with chronic kidney disease (CKD) remains unclear.

Methods

Utilizing NHANES data (2003–2006, 2013–2016), we analyzed 10,431 participants to examine associations between hemoglobin-bound AA (HbAA), glycidamide (HbGA), and CKD prevalence. Associations were evaluated through weighted multivariate logistic regression and dose-response analysis with restricted cubic splines. Additionally, toxicological profiling, target identification, and pathway enrichment analysis were performed.

Results

Higher HbAA, HbGA, and combined biomarkers were non-linearly associated, with lower CKD prevalence at higher quartiles and evidence of threshold effects on RCS. A significant negative association was observed for HbAA (highest vs. lowest quartile OR = 0.78, 95 % CI: 0.59–1.01, P-trend = 0.033) and HbGA (OR = 0.74, 95 % CI: 0.54–1.01, P-trend = 0.041). Dose-response analysis indicated a non-linear relationship, suggesting threshold effects potentially explained by hormesis, younger demographics, or confounding dietary and lifestyle factors. Computational modeling identified potential key molecular targets (TP53, AKT1, BCL2, JUN, MAPK3, TNF) that may mediate AA's biological effects.

Conclusion

The inverse relationship between AA exposure biomarkers and CKD identified in this large population-based study challenges current toxicological paradigms. This may be due to hormesis, demographic confounding, or methodological limitations. Longitudinal studies are needed to validate these paradoxical results.

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丙烯酰胺和甘油酰胺血红蛋白加合物水平与慢性肾病的关系：一项NHANES分析

背景：丙烯酰胺（AA）是一种具有实验性肾毒性的膳食污染物，但其与慢性肾脏疾病（CKD）的关系尚不清楚。方法：利用NHANES数据（2003-2006年，2013-2016年），我们分析了10431名参与者，以检查血红蛋白结合AA （HbAA）、甘油酰胺（HbGA）和CKD患病率之间的关系。通过加权多元逻辑回归和限制三次样条的剂量-反应分析来评估相关性。此外，还进行了毒理学分析、靶标鉴定和途径富集分析。结果：较高的HbAA、HbGA和联合生物标志物与较高四分位数较低的CKD患病率呈非线性相关，并有证据表明阈值效应对RCS有影响。HbAA（最高四分位数vs最低四分位数OR = 0.78, 95 % CI: 0.59-1.01, P-trend = 0.033）和HbGA （OR = 0.74, 95 % CI: 0.54-1.01, P-trend = 0.041）呈显著负相关。剂量-反应分析显示非线性关系，表明阈值效应可能由激效、年轻人口统计或混杂的饮食和生活方式因素解释。计算模型确定了可能介导AA生物学效应的潜在关键分子靶点（TP53, AKT1, BCL2， JUN, MAPK3， TNF）。结论：在这项基于人群的大型研究中发现的AA暴露生物标志物与CKD之间的负相关关系挑战了当前的毒理学范式。这可能是由于激效、人口统计学混淆或方法上的限制。需要纵向研究来验证这些矛盾的结果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Ecotoxicology and Environmental Safety 环境科学-毒理学

CiteScore

12.10

自引率

5.90%

发文量

1234

审稿时长

88 days

期刊介绍： Ecotoxicology and Environmental Safety is a multi-disciplinary journal that focuses on understanding the exposure and effects of environmental contamination on organisms including human health. The scope of the journal covers three main themes. The topics within these themes, indicated below, include (but are not limited to) the following: Ecotoxicology、Environmental Chemistry、Environmental Safety etc.