目的：观察临床表现为肾病综合征的磷脂酶A2受体（phospholipase A2 receptor，PLA2R）阴性的原发性膜性肾病（primary membranous nephropathy，PMN）患者使用利妥昔单抗（rituximab，RTX）的临床疗效，并分析疗效预测相关指标。方法：回顾性收集上海交通大学附属瑞金医院2020年3月至2024年3月间，经肾活检确诊为PLA2R阴性且临床表现为肾病综合征的19例PMN患者，所有患者均使用RTX治疗；同时匹配PLA2R阳性且临床表现为肾病综合征，并使用RTX治疗的38例PMN患者作为对照。最少随访6个月（中位12个月），观察这2组患者使用RTX的临床疗效，并分析可预测RTX治疗PLA2R阴性MN患者疗效的相关指标。结果：PLA2R阴性的PMN患者，采用RTX治疗12个月时，与基线相比，总体24 h尿蛋白定量从（9.8±4.3）g/d下降至（2.6±2.6）g/d，总体血清白蛋白从（20.3±4.3）g/L上升至（36.4±7.1）g/L（P<0.05），总体估算肾小球滤过率变化无统计学意义[（90.7±30.0）mL·min^-1·1.73m^-2比（84.4±22.19）mL·min^-1·1.73m^-2]（P>0.05）。PLA2R阴性组总体缓解率在治疗3个月（57.89%）、6个月（57.89%）、12个月（85.71%）时与PLA2R阳性组相当（P>0.05）。治疗3个月及6个月时，PLA2R阴性组的完全缓解率高于PLA2R抗体阳性组（3个月时，21.5%比0，P=0.009 8；6个月时36.84%比10.53%，P=0.030 5），差异有统计学意义。单因素logistic回归分析显示，影响PLA2R阴性PMN患者RTX治疗12个月时临床缓解的变量包括，3个月时24 h尿蛋白定量（OR=0.993，P=0.047 1）及3个月时血清白蛋白（OR=1.309，P=0.048 8）。结论：RTX治疗PLA2R阴性的PMN有效，与PLA2R阳性组相比，治疗12个月时总缓解率相当，治疗3个月时完全缓解率略胜一筹。RTX治疗3个月时24 h尿蛋白定量及血清白蛋白水平可能作为PLA2R阴性PMN患者12个月时临床缓解情况的预测指标。

Objective To evaluate the clinical efficacy of rituximab (RTX) in patients with phospholipase A2 receptor (PLA2R)-negative primary membranous nephropathy (PMN) presenting as nephrotic syndrome, and to identify predictors for treatment efficacy. Methods This retrospective cohort study included 19 biopsy-proven PLA2R-negative PMN patients with nephrotic syndrome who received RTX at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine between March 2020 and March 2024. Additionally, 38 PLA2R-positive PMN patients with nephrotic syndrome who received RTX were matched as controls. All patients were followed for at least 6 months (median = 12 months) to evaluate the clinical efficacy of RTX in both groups and to analyze potential predictors of treatment efficacy in PLA2R-negative MN patients. Results In PLA2R-negative PMN patients treated with RTX for 12 months, the 24-hour proteinuria significantly decreased from (9.8±4.3) g/d to (2.6±2.6) g/d and serum albumin increased from (20.3±4.3) g/L to (36.4±7.1) g/L (P<0.05). The overall change in estimated glomerular filtration rate showed no statistical significance [(90.7±30.0) mL·min^-1·1.73 m^-2 vs. (84.4±22.19) mL·min^-1·1.73 m^-2] (P>0.05). Overall remission rates in the PLA2R-negative group at 3 months (57.89%), 6 months (57.89%), 12 months (85.71%) were comparable to those in the PLA2R-positive group (P>0.05). However, the complete remission rate was significantly higher in the PLA2R-negative group at 3 months (21.5% vs. 0%, P=0.009 8) and 6 months (36.84% vs. 10.53%, P=0.030 5), indicating statistical significance. The univariate logistic regression analysis showed that factors influencing clinical remission at 12 months of RTX treatment in PLA2R-negative PMN patients were 3-month 24-hour proteinuria (OR=0.993, P=0.047 1) and 3-month serum albumin (OR=1.309, P=0.048 8). Conclusion RTX treatment is effective in treating PLA2R-negative PMN. Compared with the PLA2R-positive group, the overall remission rate at 12 months was comparable, with a slightly higher complete remission rate at 3 months. The 3-month 24-hour proteinuria and 3-month serum albumin levels may serve as potential predictors for clinical remission at 12 months in PLA2R-negative PMN patients.