Institute of Public Health, Guangzhou Medical University & Guangzhou Center for Disease Control and Prevention, Guangzhou, 510440, China; School of Public Health, Southern Medical University, Guangzhou, 510515, China.
School of Public Health, Southern Medical University, Guangzhou, 510515, China.
Environ Pollut. 2024 Nov 15;361:124865. doi: 10.1016/j.envpol.2024.124865. Epub 2024 Aug 30.
Per- and polyfluoroalkyl substances (PFAS) have been linked to kidney function. Studies have shown that PFAS can cause changes in lipid metabolism and that lipids play an important role in regulating kidney function. However, few studies have explored the overall impact of PFAS mixture on kidney function. Moreover, the mechanisms by which PFAS influences kidney function remain unclear. This study was performed to investigate the overall impact of PFAS mixture on kidney function indexes, dissect the mechanism by which PFAS affect kidney function by analyzing lipid molecule profiles, and analyze the associations between different subclasses of lipids and kidney function indexes. We measured blood PFAS levels and kidney function indexes in a community population containing 278 males. Metabolomic analysis detected 332 lipid molecules. A quantile-based g-computation model was applied to assess the overall effect of PFAS mixture on kidney function index, and revealed that PFAS mixture were associated with a higher level of uric acid (UA). Linear regression analysis demonstrated a positive association between PFOA and UA, and logistic regression analysis indicated a positive association between PFOA and hyperuricemia odds. Notably, none of the PFAS were associated with the estimated glomerular filtration rate, indicating that PFAS didn't have an obvious effect on glomerular filtration. Further analysis identified 20 lipid molecules associated with both PFOA and UA. High-dimensional mediation effect analysis showed that seven lipid molecules (one glycerophospholipid, three fatty acyls, and three prenol lipids) mediated the association between PFOA and UA. Additionally, quantile-based g-computation analysis revealed positive associations between specific lipid subclasses-mainly fatty acid esters, fatty acids and conjugates, and sesquiterpenoids-and kidney function indexes. Our findings provide insights into the renal toxicity of PFAS and may also lead to more in-depth investigations using animal models and other population studies.
全氟和多氟烷基物质（PFAS）与肾功能有关。研究表明，PFAS 可导致脂质代谢改变，而脂质在调节肾功能方面发挥着重要作用。然而，很少有研究探讨 PFAS 混合物对肾功能的整体影响。此外，PFAS 影响肾功能的机制尚不清楚。本研究旨在探讨 PFAS 混合物对肾功能指标的整体影响，通过分析脂质分子谱来剖析 PFAS 影响肾功能的机制，并分析不同亚类脂质与肾功能指标之间的关系。我们测量了一个包含 278 名男性的社区人群的血液 PFAS 水平和肾功能指标。代谢组学分析检测到 332 种脂质分子。基于分位数的 g 计算模型用于评估 PFAS 混合物对肾功能指标的整体影响，结果表明 PFAS 混合物与尿酸（UA）水平升高有关。线性回归分析表明 PFOA 与 UA 呈正相关，逻辑回归分析表明 PFOA 与高尿酸血症的几率呈正相关。值得注意的是，PFAS 与估算的肾小球滤过率均无明显相关性，这表明 PFAS 对肾小球滤过没有明显影响。进一步分析确定了与 PFOA 和 UA 均相关的 20 种脂质分子。高维中介效应分析表明，七种脂质分子（一种甘油磷脂、三种脂肪酰基和三种异戊二烯脂质）介导了 PFOA 与 UA 之间的关联。此外，基于分位数的 g 计算分析揭示了特定脂质亚类（主要是脂肪酸酯、脂肪酸及其缀合物和倍半萜烯）与肾功能指标之间的正相关关系。我们的研究结果为 PFAS 的肾毒性提供了新的认识，也可能促使我们使用动物模型和其他人群研究进行更深入的研究。
