Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.
Institute of Nephrology, Peking University, Beijing, China.
Nephrol Dial Transplant. 2018 Sep 1;33(9):1558-1563. doi: 10.1093/ndt/gfx295.
Rituximab had been shown to be effective in inducing remission of nephrotic syndrome in patients with idiopathic membranous nephropathy (iMN). This study applied rituximab therapy for 36 non-responsive iMN patients to investigate its effects and safety.
Thirty-six iMN patients who were non-responsive to prior immunosuppression were enrolled. Rituximab was used for B-cell depletion in patients, with a goal of <5 B cells/mm3 in the circulation. After completing the study, patients were monitored for a median of 12.0 months [interquartile range (IQR) 9.0-19.3].
Fifteen of the 36 (41.7%) patients achieved partial (n = 13) or complete (n = 2) response to the rituximab treatment. The median time for achieving partial response was 4.0 months (IQR 3.0-6.0). The responders had relatively lower levels (118 ± 112 U/mL versus 345 ± 357 U/mL, P = 0.03) of anti-phospholipase 2 receptor (PLA2R) antibodies before the rituximab treatment, and all of them achieved antibody depletion or reduction. B-cell depletion was achieved in all patients. Renal function remained stable in the responders [estimated glomerular filtration rate (eGFR) 53.3 ± 40.5 versus 55.6 ± 33.2 mL/min/1.73 m2, P = 0.67] but deteriorated in the non-responders (eGFR 57.5 ± 29.3 versus 45.3 ± 32.8 mL/min/1.73 m2, P = 0.02) with two patients reaching end-stage kidney disease. Two of the 15 patients relapsed during the follow-up period with anti-PLA2R antibody reoccurrence and B-cell reconstitution. The second course of rituximab combined with tacrolimus induced a faster partial response again in one patient.
Rituximab therapy could induce remission of proteinuria and stabilization of renal function in non-responsive iMN patients, even those with damaged renal function. Anti-PLA2R antibodies may be used as a marker for individualized rituximab dosage and treatment monitoring.
利妥昔单抗已被证明可有效诱导特发性膜性肾病（iMN）患者肾病综合征缓解。本研究对 36 例对既往免疫抑制治疗无反应的 iMN 患者应用利妥昔单抗治疗，以评估其疗效和安全性。
共纳入 36 例对既往免疫抑制治疗无反应的 iMN 患者。采用利妥昔单抗清除 B 细胞，目标为循环中 B 细胞<5 个/mm3。研究结束后，中位随访 12.0 个月（IQR：9.0-19.3）。
15 例（41.7%）患者对利妥昔单抗治疗部分（n=13）或完全（n=2）缓解。达到部分缓解的中位时间为 4.0 个月（IQR：3.0-6.0）。缓解者治疗前抗磷脂酶 A2 受体（PLA2R）抗体水平相对较低（118±112 U/mL 比 345±357 U/mL，P=0.03），且均实现抗体耗竭或降低。所有患者均达到 B 细胞耗竭。缓解者肾功能保持稳定[估算肾小球滤过率（eGFR）53.3±40.5 比 55.6±33.2 mL/min/1.73 m2，P=0.67]，而无反应者恶化[eGFR 57.5±29.3 比 45.3±32.8 mL/min/1.73 m2，P=0.02]，其中 2 例进展至终末期肾病。15 例缓解者中有 2 例在随访期间复发，出现抗 PLA2R 抗体再出现和 B 细胞重建。1 例患者再次接受利妥昔单抗联合他克莫司治疗后更快达到部分缓解。
利妥昔单抗治疗可诱导无反应性 iMN 患者蛋白尿缓解和肾功能稳定，甚至在肾功能受损的患者中也如此。抗 PLA2R 抗体可作为利妥昔单抗剂量个体化和治疗监测的标志物。
