Impact of per- and polyfluoroalkyl substances exposure on renal dysfunction: Integrating epidemiological evidence with mechanistic insights

IF 7.3 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Environmental Pollution Pub Date : 2025-06-28 DOI:10.1016/j.envpol.2025.126744

Weitao Su , Ziwen An , Yayuan Mei , Zhenzhen Tan , Zexuan Jiang , Xiuli Zeng , Zhiqiang Dong , Ming Yang , Jingtao Wu , Huicai Guo , Ang Li

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Abstract

Renal dysfunction poses a growing global health burden, yet the role of environmental contaminants like per- and polyfluoroalkyl substances (PFAS), particularly their underlying mechanisms, remains understudied. This cross-sectional study included 2801 adults from North China (Shijiazhuang and Baoding City). Plasma concentrations of 21 legacy and alternative PFAS were quantified via ultra-high-performance liquid chromatography-tandem mass spectrometry. Renal function markers (serum creatinine (SCr), serum uric acid (SUA), SUA to SCr ratio (SUA/SCr), blood urea nitrogen (BUN), BUN to SCr ratio (BUN/SCr), estimated glomerular filtration rate (eGFR)) and inflammatory markers were assessed. Multivariable linear regression and quantile g-computation evaluated individual and mixture effects. Receiver operating characteristic (ROC) analysis assessed renal markers’ predictive ability for PFAS. Mediation analysis investigated the role of inflammatory markers, while bioinformatics explored molecular mechanisms. Nine PFAS demonstrated significant associations with elevated SCr, SUA, SUA/SCr, BUN, BUN/SCr, or reduced eGFR. Notably, perfluorooctanesulfonic acid (PFOS) exhibited concurrent associations with SCr, SUA, BUN, and eGFR. PFAS mixtures were linked to increased SCr, SUA, SUA/SCr, BUN, and decreased eGFR. PFOS and perfluorooctanoic acid (PFOA) contributed most to eGFR decline and SUA elevation, respectively. ROC analysis demonstrated superior predictive performance of renal biomarkers for PFOS. Inflammatory markers significantly mediated PFAS (particularly PFOS)-renal dysfunction associations. Bioinformatics implicated lipid metabolism dysregulation and peroxisome proliferator-activated receptor (PPAR) signaling disruption as key mechanisms. In conclusion, PFAS exposure, especially PFOS, was associated with renal dysfunction, mediated primarily by inflammation and lipid metabolism. These findings provide critical mechanistic insights for developing prevention and management strategies against PFAS-associated renal dysfunction.

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全氟和多氟烷基物质暴露对肾功能障碍的影响：综合流行病学证据和机制见解

肾功能障碍对全球健康造成的负担日益加重，但全氟和多氟烷基物质（PFAS）等环境污染物的作用，特别是其潜在机制，仍未得到充分研究。本横断面研究包括华北地区（石家庄和保定市）2801名成年人。采用超高效液相色谱-串联质谱法定量21种遗留PFAS和替代PFAS的血浆浓度。评估肾功能指标（血清肌酐（SCr）、血清尿酸（SUA）、SUA/SCr比值（SUA/SCr）、血尿素氮（BUN）、BUN/SCr比值（BUN/SCr）、肾小球滤过率（eGFR）及炎症指标）。多变量线性回归和分位数g计算评估了个体和混合效应。受试者工作特征（ROC）分析评估肾脏标志物对PFAS的预测能力。中介分析研究炎症标志物的作用，而生物信息学探索分子机制。9种PFAS与SCr、SUA、SUA/SCr、BUN、BUN/SCr或eGFR降低显著相关。值得注意的是，全氟辛烷磺酸（PFOS）与SCr、SUA、BUN和eGFR同时存在关联。PFAS混合物与SCr、SUA、SUA/SCr、BUN升高和eGFR降低有关。全氟辛烷磺酸和全氟辛酸（PFOA）分别对eGFR下降和SUA升高贡献最大。ROC分析显示肾脏生物标志物对全氟辛烷磺酸具有优越的预测性能。炎症标志物显著介导PFAS（尤其是PFOS）与肾功能障碍的关联。生物信息学暗示脂质代谢失调和过氧化物酶体增殖物激活受体（PPAR）信号中断是关键机制。总之，全氟辛烷磺酸暴露，尤其是全氟辛烷磺酸，与肾功能障碍有关，主要由炎症和脂质代谢介导。这些发现为制定预防和管理pfas相关肾功能障碍的策略提供了关键的机制见解。

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来源期刊

Environmental Pollution 环境科学-环境科学

CiteScore

16.00

自引率

6.70%

发文量

2082

审稿时长

2.9 months

期刊介绍： Environmental Pollution is an international peer-reviewed journal that publishes high-quality research papers and review articles covering all aspects of environmental pollution and its impacts on ecosystems and human health. Subject areas include, but are not limited to: • Sources and occurrences of pollutants that are clearly defined and measured in environmental compartments, food and food-related items, and human bodies; • Interlinks between contaminant exposure and biological, ecological, and human health effects, including those of climate change; • Contaminants of emerging concerns (including but not limited to antibiotic resistant microorganisms or genes, microplastics/nanoplastics, electronic wastes, light, and noise) and/or their biological, ecological, or human health effects; • Laboratory and field studies on the remediation/mitigation of environmental pollution via new techniques and with clear links to biological, ecological, or human health effects; • Modeling of pollution processes, patterns, or trends that is of clear environmental and/or human health interest; • New techniques that measure and examine environmental occurrences, transport, behavior, and effects of pollutants within the environment or the laboratory, provided that they can be clearly used to address problems within regional or global environmental compartments.