全氟烷基和多氟烷基物质(PFAS)是大量制造的不可生物降解的化合物。尽管人们对全球污染物的认识日益提高,PFAS暴露对人类健康的影响尚不清楚,人们越来越担心对肾功能的不利影响。因此,我们进行了一项范围审查,以总结和确定PFAS暴露与肾脏健康之间的认识差距.
我们系统地搜索了PubMed,EMBASE,EBSCO全球健康,世界卫生组织全球指数,和WebofScience发表于1990年至2018年的研究。我们纳入了流行病学研究,药代动力学,或PFAS暴露和肾脏相关健康的毒理学,包括临床,组织学,分子,以及与肾脏疾病相关的代谢结果,或与肾脏的药代动力学作用有关的结果。
我们确定了74项研究,包括21名流行病学,13药代动力学,和40项毒理学研究。三项基于人群的流行病学研究表明,PFAS暴露与肾功能降低之间存在关联。除了毒理学研究(n=10),显示PFAS暴露引起的肾小管组织学和细胞变化,药代动力学研究(n=5)证明肾脏是主要的消除途径,有活跃的近端小管运输。在几项研究中(n=17),PFAS暴露改变了几个与肾脏疾病相关的途径,包括氧化应激途径,过氧化物酶体增殖物激活的受体途径,NF-E2相关因子2途径,部分上皮间质转化,通过肌动蛋白丝建模增强内皮通透性。
越来越多的证据表明,PFAS正在出现对肾脏健康的环境威胁;然而,在我们的理解中仍然存在一些重要的差距。
Per- and polyfluoroalkyl substances (PFASs) are a large group of manufactured nonbiodegradable compounds. Despite increasing awareness as global pollutants, the impact of PFAS exposure on human health is not well understood, and there are growing concerns for adverse effects on kidney function. Therefore, we conducted a scoping
review to summarize and identify gaps in the understanding between PFAS exposure and kidney health.
We systematically searched PubMed, EMBASE, EBSCO Global Health, World Health Organization Global Index, and Web of Science for studies published from 1990 to 2018. We included studies on the epidemiology, pharmacokinetics, or toxicology of PFAS exposure and kidney-related health, including clinical, histologic, molecular, and metabolic outcomes related to kidney disease, or outcomes related to the pharmacokinetic role of the kidneys.
We identified 74 studies, including 21 epidemiologic, 13 pharmacokinetic, and 40 toxicological studies. Three population-based epidemiologic studies demonstrated associations between PFAS exposure and lower kidney function. Along with toxicology studies (n=10) showing tubular histologic and cellular changes from PFAS exposure, pharmacokinetic studies (n=5) demonstrated the kidneys were major routes of elimination, with active proximal tubule transport. In several studies (n=17), PFAS exposure altered several pathways linked to kidney disease, including oxidative stress pathways, peroxisome proliferators-activated receptor pathways, NF-E2-related factor 2 pathways, partial epithelial mesenchymal transition, and enhanced endothelial permeability through actin filament modeling.
A growing body of evidence portends PFASs are emerging environmental threats to kidney health; yet several important gaps in our understanding still exist.