Abstract：
Chronic Kidney Disease (CKD), closely linked to environmental factors, poses a significant public health challenge. This study, based on 529 triple-repeated measures from key national environmental pollution area and multiple gene-related public databases, employs various epidemiological and bioinformatics models to assess the impact of combined heavy metal exposure (Chromium [Cr], Cadmium [Cd], and Lead [Pb]) on early renal injury and CKD in the elderly. Introducing the novel Enviro-Target Mendelian Randomization method, our research explores the causal relationship between metals and CKD. The findings indicate a positive correlation between increased levels of metal and renal injury, with combined exposure caused renal damage more significantly than individual exposure. The study reveals that metals primarily influence CKD development through oxidative stress and metal ion resistance pathways, focusing on three related genes (SOD2, MPO, NQO1) and a transcription factor (NFE2L2). Metals were found to regulate oxidative stress levels in the body by increasing the expression of SOD2, MPO, NQO1, and decreasing NFE2L2, leading to CKD onset. Our research establishes a new causal inference framework linking environmental pollutants-pathways-genes-CKD, assessing the impact and mechanisms of metal exposure on CKD. Future studies with more extensive in vitro evidence and larger population are needed to validate.
摘要：
慢性肾脏疾病（CKD），与环境因素密切相关，构成了重大的公共卫生挑战。这项研究,基于来自国家重点环境污染领域和多个基因相关公共数据库的529次重复措施，采用各种流行病学和生物信息学模型来评估联合重金属暴露的影响(铬[Cr]，镉[Cd],和铅[Pb]）对老年人早期肾损伤和CKD的影响。介绍新的环境靶向孟德尔随机化方法，我们的研究探讨了金属与CKD之间的因果关系。研究结果表明，金属水平升高与肾损伤呈正相关，联合暴露引起的肾损害比单独暴露更显著。研究表明，金属主要通过氧化应激和金属离子抗性途径影响CKD的发展，关注三个相关基因(SOD2、MPO、NQO1）和转录因子（NFE2L2）。发现金属通过增加SOD2，MPO的表达来调节体内的氧化应激水平，NQO1和NFE2L2降低，导致CKD发病。我们的研究建立了一个新的因果推断框架，将环境污染物-途径-基因-CKD联系起来，评估金属暴露对CKD的影响和机制。未来的研究需要更广泛的体外证据和更大的人群来验证。
