【作者】 张玲；

【导师】 袁敏；

【作者基本信息】 安徽医科大学 ， 社会医学与卫生事业管理， 2025， 硕士

【摘要】 背景:职业和环境接触重金属是成人肾脏健康的重要风险因素之一。青少年作为特殊的生命阶段,对环境重金属暴露表现出更高的敏感性和脆弱性,青春期的肾脏损伤可能会产生深远的长期影响。然而,目前研究重金属联合暴露以及重金属之间是如何相互作用对青少年肾脏健康的影响相对较少。目的:本研究旨在从重金属联合暴露水平和重金属之间相互作用的网络结构两个方面探讨重金属暴露对青少年肾功能的影响,识别不同风险亚组、参与网络重新布局的关键金属与相关肾脏参数的关联。方法:本研究收集美国健康和营养检查调查(NHANES)2009年至2018年的青少年数据,调整潜在的混杂因素,探索3种血液金属(铅、镉、汞)和11种尿液重金属(钡、镉、钴、铯、钼、铅、锑、铊、钨、汞、砷)与相关肾功能参数(估计肾小球滤过率(eGFR)、血清尿酸(SUA)、血尿素氮(BUN)、尿白蛋白/肌酐比值(ACR)、尿白蛋白(UA)、收缩压(SBP))的关系。首先使用k-medoids聚类算法基于重金属水平对人群进行风险分层,并分析不同风险亚组与肾功能参数的关联。其次,使用差异网络分析,进一步识别参与不同肾功能参数网络重新布局的金属对。另外还对性别等变量进行了分层分析。结果:本研究初始纳入6554名12-19岁的青少年,保留具有完整重要人口统计学变量、血液或尿液金属和肾功能参数,剔除无效数据后共有4126名研究对象。通过无监督聚类分析分别识别了基于血液和尿液中金属的三种主要暴露模式,结果表明金属联合暴露模式与部分肾脏参数存在显著的关联性。具体而言,对于血液金属联合暴露,第二组和第三组的SUA均显著地高于第一组,效应值分别为0.089(95%CI:0.011～0.167,p=0.026)、0.129(95%CI:0.044～0.214,p=0.003)。对于尿液金属联合暴露,第二组的e GFR显著地低于第一组,效应值为-18.547(95%CI:-23.743～-13.350,p<0.001);第三组的e GFR显著地高于第一组,效应值为12.853(95%CI:8.908～16.799,p<0.001)。网络分析结果表明不同的金属对参与了不同肾脏参数的网络重组,具体可分为三种类型的网络重新布局:正常组显著,异常组不显著;正常组不显著,异常组显著;以及两组均显著且差异显著模式。其中三对金属(As-Co、As-Sb、Cs-Tu)均参与了e GFR、SUA、BUN、ACR的网络重组,但其作用模式存在参数特异性差异。敏感性分析表明,在男性亚组中,金属对MO-PB和CO-MO的相关性在e GFR组从低到高中显著加强,而在女性亚组中,金属对的相关性在e GFR组中没有显著差异。结论:血液和尿液中金属联合暴露模式与部分肾脏参数之间存在显著关联性。高水平金属联合暴露模式的人群有相对较高的血清尿酸值及较低的估计肾小球滤过率。同时,重金属网络重组为预测青少年肾脏参数提供了有价值的独立见解,并显示了与性别的显著交互作用。更多还原

【Abstract】 Background:Occupational and environmental exposure to heavy metals is one of the important risk factors for kidney health in adults.As a special life stage,adolescents show higher sensitivity and vulnerability to environmental heavy metal exposure,and kidney damage in adolescence may have profound long-term effects.However,there are relatively few studies on the effects of combined exposure to heavy metals and how heavy metals interact with each other on kidney health in adolescents.Objective:This study aims to explore the effects of heavy metal exposure on renal function in adolescents from two aspects:the combined exposure level of heavy metals and the network structure of the interaction between heavy metals,and to identify the associations between different risk subgroups,different metal pairs involved in network rearrangement and related renal parameters.Methods:This study collected adolescent data from the National Health and Nutrition Examination Survey(NHANES)from 2009 to 2018,adjusted for potential confounding factors,and explored the relationship between 3 blood metals(lead,cadmium,and mercury)and 11 urine heavy metals(barium,cadmium,cobalt,cesium,molybdenum,lead,antimony,thallium,tungsten,mercury,and arsenic)and related renal function parameters(estimated glomerular filtration rate(e GFR),serum uric acid(SUA),blood urea nitrogen(BUN),urine albumin/creatinine ratio(ACR),urine albumin(UA),and systolic blood pressure(SBP)).First,the k-medoids clustering algorithm was used to stratify the population based on heavy metal levels,and the association between different risk subgroups and renal function parameters was analyzed.Secondly,differential network analysis was used to further identify metal pairs involved in the re-layout of different renal function parameter networks.In addition,we also performed stratified analysis on variables such as gender.Results:This study initially included 6554 adolescents aged 12-19 years,retaining complete important demographic variables,blood or urine metals and renal function parameters.After excluding invalid data,a total of 4126 subjects were included.Unsupervised cluster analysis identified three main exposure patterns based on metals in blood and urine,respectively,and the results showed that the combined metal exposure pattern was significantly associated with some renal parameters.Specifically,for combined blood metal exposure,the SUA of the second and third groups was significantly higher than that of the first group,with effect sizes of 0.089(95%CI:0.011～0.167,p=0.026)and 0.129(95%CI:0.044～0.214,p=0.003),respectively.For the combined exposure of urinary metals,the e GFR of the second group was significantly lower than that of the first group,with an effect value of-18.547(95%CI:-23.743～-13.350,p<0.001);the e GFR of the third group was significantly higher than that of the first group,with an effect value of 12.853(95%CI:8.908～16.799,p<0.001).The results of network analysis showed that different metal pairs were involved in the network reorganization of different renal parameters,which can be divided into three types of network reorganization:the normal group was significant,the abnormal group was not significant;the normal group was not significant,the abnormal group was significant;and both groups were significant and the difference was significant.Among them,three pairs of metals(As-Co,As-Sb,Cs-Tu)were involved in the network reorganization of e GFR,SUA,BUN,and ACR,but their action modes had parameter-specific differences.Sensitivity analysis showed that in the male subgroup,the associations of metal pairs for MO-PB and CO-MO were significantly strengthened from low to high e GFR groups,while in the female subgroup,the associations of metal pairs were not significantly different among e GFR groups.Conclusion:There were significant associations between metal co-exposure patterns in blood and urine and some renal parameters.People with high-level metal co-exposure patterns had relatively higher serum uric acid values and lower estimated glomerular filtration rate.Meanwhile,heavy metal network reorganization provided valuable independent insights into predicting renal parameters in adolescents and showed significant interactions with gender.更多还原