Abstract:

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.

Key words: Primary membranous nephropathy, Target antigen, Non-invasive diagnosis, Risk stratification