Combined Anti-Phospholipase A2 Receptor and Early B-Cell Reconstitution Predict Rituximab Response in Membranous Nephropathy

A retrospective observational design was adopted for this clinical investigation. 105 anti-phospholipase A2 receptor (PLA2R)-associated membranous nephropathy (MN) patients who received standard rituximab (RTX) treatment at Ganzhou People's Hospital between January 2023 and December 2024 were enrolled, 102 patients were retained after exclusion. They were divided into remission and non-remission groups at 12-month follow-up. The receiver operating characteristic (ROC) curve assessed the predictive performance of anti-PLA2R measurement, early B-cell recovery assessment, and their combination. Multivariate Cox regression identified independent risk factors for poor treatment response. Patients were stratified by cut-off values, and cumulative remission rates were compared using the Log-rank test. Of all enrolled patients, 66 (64.7%) achieved remission, and 36 (35.3%) did not. Baseline characteristics were comparable between groups (all P > 0.05). Non-remission patients had higher baseline anti-PLA2R levels and higher rates of early B-cell reconstitution (both P < 0.001). ROC analysis showed single anti-PLA2R predicted poor RTX efficacy with an area under the curve (AUC) = 0.756 [95% confidence interval (CI): 0.663-0.849], while early B-cell reconstitution yielded an AUC = 0.681 (95% CI: 0.567-0.794). Their combined prediction achieved an AUC of 0.854 (95% CI: 0.784-0.924), superior to the single indicators (all P < 0.05). Multivariate analysis identified baseline anti-PLA2R > 155 RU/mL and early B-cell reconstitution as independent risk factors for unsatisfactory RTX response (all P < 0.05). Log-rank test revealed differences in cumulative remission rates across risk subgroups (P < 0.001): low-risk (72.5% at 6 months, 90.0% at 12 months), medium-risk (40.5%, 64.3%), and high-risk (15.0%, 30.0%). In this retrospective single-center cohort, the combined baseline anti-PLA2R titer and early B-cell reconstitution showed promising discriminative performance for RTX outcomes in an internal cohort evaluation. This represents an internally evaluated risk-stratification approach; prospective external validation is mandatory prior to any clinical application.