膜性肾病（MN）是一种由免疫介导的肾小球肾炎，近年来发病率呈显著上升趋势，但病因未明。我们前期研究发现人群尿镉浓度、血清IL-4和IgG4水平升高均与MN发病风险增加有关；细胞预实验结果提示镉可能参与了Ca2+-CaN-NFAT信号通路的激活。已有研究表明IL-4可诱导IgG4的分泌。由此我们提出科学假设：重金属镉是否通过Ca2+-CaN-NFAT信号途径调控细胞因子IL-4的表达，从而影响IgG4的分泌水平而介导了MN的发生？本研究拟通过人群调查、动物模型和细胞实验相结合的方法，采用ICP-MS、免疫荧光、qRT-PCR、Western blot、共聚焦激光扫描显微镜、基因敲除、细胞转染等技术，探讨镉暴露对MN发病风险的影响及Ca2+-CaN-NFAT信号通路在镉致MN发病中的作用及其机制。本研究结果将有助于进一步揭示MN的病因及发病机制，并为采取精准预防措施及指导临床治疗提供理论依据。

Membranous nephropathy (MN) is an immune-mediated glomerulonephritis, and its incidence has shown a significant upward trend in recent years, but the etiology is unknown. Our previous study found that increased urinary cadmium concentration, serum IL-4 and IgG4 levels in the population were all associated with increased risk of MN; the results of cell pre-experiment suggested that cadmium was involved in the activation of Ca2+-CaN-NFAT signaling pathway. Studies have shown that IL-4 can induce IgG4 secretion. Thus, we propose the scientific hypothesis: whether cadmium regulates cytokine IL-4 expression through Ca2+-CaN-NFAT signaling pathways, and then affects IgG4 secretion levels and mediate the occurrence of MN? This study intends to explore the effects of cadmium exposure on the MN risk, and the role and mechanism of Ca2+-CaN-NFAT signaling pathway in cadmium-induced MN by using ICP-MS, immunofluorescence, qRT-PCR, Western-blot, confocal laser scanning microscopy, gene knockout, and cell transfection techniques through a combination of population surveys, animal models and cell experiments. Findings of this study will contribute to further reveal the etiology and pathogenesis of MN, and provide theoretical basis for taking precise preventive measures and guiding clinical treatment.