原发性膜性肾病（primary membranous nephropathy，PMN）发病率在全球范围内显著上升，中国数据显示其以每年13%的速率增长，已成为40岁以上人群肾病综合征的首要原因。PMN的诊断传统上依赖肾穿刺活检，但近年来的研究为无创诊断提供了新方向。2009年，抗磷脂酶A2受体（phospholipase A2 receptor，PLA2R）抗体的发现是PMN研究的里程碑，随后其他靶抗原（如THSD7A、NELL-1等）的鉴定进一步推动了发病机制的阐明。血清PLA2R抗体检测具有高特异度，但灵敏度有限，可能漏诊非PLA2R相关病例。基于全基因组关联研究发现的易感基因位点（如PLA2R1、*HLA-DQA1*等）与血清抗体联合建立的联合疾病风险评分（combined risk score, CRS），显著提高了无创诊断的准确率（受试者操作特征曲线下面积达0.96）。此外，肠道微生物组分析也显示出诊断潜力，但其临床应用仍需优化。PMN的自然病程异质性显著，约1/3的患者可自发缓解，另有1/3的患者进展为肾功能减退。年龄、蛋白尿水平、eGFR、PLA2R抗体滴度及肾小管间质病变程度是预后的关键预测因素。CRS联合临床模型（如年龄、蛋白尿、eGFR等）可有效鉴别高危患者，指导精准治疗。传统的PMN治疗方案（如激素联合烷化剂或钙调磷酸酶抑制剂）虽有效，但毒副反应明显。近年来，以利妥昔单抗（rituximab，RTX）为代表的抗CD20单抗成为一线用药，显著改善了疗效，但其对于部分患者仍无效。新型生物制剂及补体通路抑制剂为耐药患者提供了新选择。联合治疗策略（如RTX与他克莫司联用）也在探索中，但需权衡疗效与安全性。未来需进一步优化风险分层和个体化治疗策略，以改善PMN患者的长期预后。

Primary membranous nephropathy (PMN) has seen a significant global rise in incidence, with data from China showing an annual growth of 13%, making it the leading cause of nephrotic syndrome in people over 40 years old. The diagnosis of PMN traditionally depends on renal biopsy, but recent studies have provided new directions for non-invasive diagnosis. The discovery of anti-phospholipase A2 receptor (PLA2R) antibodies in 2009 marked a milestone in PMN research, and the identification of other target antigens (such as THSD7A and NELL-1) further advanced the understanding of the pathogenesis. Serum PLA2R antibody detection has high specificity but limited sensitivity, potentially lea-ding to missed diagnosis of non-PLA2R-related cases. The combined disease risk score integrating susceptibility loci identified through genome-wide association studies (GWAS) (such as PLA2R1 and HLA-DQA1) with serum antibodies has significantly improved the accuracy of non-invasive diagnosis (area under the receiver operating characteristic curve reaching 0.96). Additionally, gut microbiome analysis demonstrates diagnostic potential, though its clinical application requires further optimization. In terms of advances in prognostic assessment, PMN exhibits remarkable heterogeneity in its natural course, with approximately one-third of patients achieving spontaneous remission and another one-third progressing to renal function decline. Age, proteinuria level, eGFR, PLA2R antibody titer, and the extent of tubulointerstitial lesions are key prognostic predictors. A model combining clinical risk score (CRS) with clinical parameters (such as age, proteinuria, and eGFR) can effectively identify high-risk patients and guide precision treatment. Traditional regimens (such as hormone combined with alkylating agents or calcineurin inhibitors) are effective but have significant toxic side effects. In recent years, anti-CD20 monoclonal antibodies, represented by rituximab (RTX), have become first-line treatments, substantially improving efficacy, though they remain ineffective for some patients. Novel biologics and complement pathway inhibitors provide new options for treatment-resistant patients. Combination strategies (such as RTX combined with tacrolimus) are under investigation, but the balance between efficacy and safety needs to be carefully considered. Future efforts should focus on further optimizing risk stratification and individualized treatment strategies to improve the long-term prognosis of PMN patients.