Ma Lianzi, Yang Li, Zheng Jing
Nephrology Department, Nanfang Hospital, Guangzhou, 510515, People's Republic of China.
Drug Des Devel Ther. 2025 Aug 18;19:7059-7067. doi: 10.2147/DDDT.S538971. eCollection 2025.
This study aims to identify influencing factors associated with the efficacy of rituximab in treating refractory membranous nephropathy (MN), characterized by persistent proteinuria and unresponsive to conventional immunosuppressive therapies. We sought to determine clinical and biochemical predictors for positive therapeutic outcomes and optimize patient selection criteria.
A total of 160 patients with biopsy-confirmed refractory MN (meeting criteria of eGFR > 30 mL/min/1.73 m², significant proteinuria, positive PLA2R-Ab, and prior treatment failure) were studied. Patients received rituximab (375 mg/m²) with 24-month monitoring. Baseline demographic, clinical, and biochemical data underwent univariate and multivariate logistic regression analyses, while ROC curve analysis evaluated predictive accuracy.
Responders (n=113) exhibited higher serum albumin, lower serum creatinine, reduced 24-hour urine protein, higher eGFR, and lower PLA2R-Ab levels (all P < 0.001) versus non-responders (n=47). Multivariate analysis identified these as independent predictors. The combined indices yielded an AUC of 0.99 (with 93.8% sensitivity and 97.9% specificity; P < 0.001), demonstrating excellent accuracy for identifying patients most likely to benefit from rituximab therapy.
Rituximab demonstrates efficacy in treating refractory MN, with specific clinical and biochemical markers providing significant predictors of treatment success. The biomarker combination (serum albumin, creatinine, 24-hour urine protein, eGFR, PLA2R-Ab) offers exceptional predictive accuracy for treatment outcomes, providing clinicians with a practical tool to guide personalized treatment decisions and optimize resource allocation in refractory MN management.
本研究旨在确定与利妥昔单抗治疗难治性膜性肾病(MN)疗效相关的影响因素,难治性MN的特征为持续性蛋白尿且对传统免疫抑制治疗无反应。我们试图确定治疗阳性结果的临床和生化预测指标,并优化患者选择标准。
共研究了160例经活检确诊的难治性MN患者(符合估算肾小球滤过率(eGFR)>30 mL/min/1.73 m²、大量蛋白尿、抗磷脂酶A2受体抗体(PLA2R-Ab)阳性及既往治疗失败的标准)。患者接受利妥昔单抗(375 mg/m²)治疗,并进行24个月的监测。对基线人口统计学、临床和生化数据进行单因素和多因素逻辑回归分析,同时采用ROC曲线分析评估预测准确性。
与未缓解者(n = 47)相比,缓解者(n = 113)的血清白蛋白水平更高、血清肌酐水平更低、24小时尿蛋白减少、eGFR更高且PLA2R-Ab水平更低(所有P < 0.001)。多因素分析确定这些为独立预测指标。联合指标的曲线下面积(AUC)为0.99(敏感性为93.8%,特异性为97.9%;P < 0.001),表明在识别最可能从利妥昔单抗治疗中获益的患者方面具有出色的准确性。
利妥昔单抗在治疗难治性MN方面显示出疗效,特定的临床和生化标志物可作为治疗成功的重要预测指标。生物标志物组合(血清白蛋白、肌酐、24小时尿蛋白、eGFR、PLA2R-Ab)对治疗结果具有出色的预测准确性,为临床医生提供了一个实用工具,以指导难治性MN管理中的个性化治疗决策并优化资源分配。