奥妥珠单抗治疗难治及高危磷脂酶A2受体相关膜性肾病的疗效观察  

Obinutuzumab in treatment of high risk or refractory phospholipase A2 receptor associated membranous nephropathy

作　　者：陈独群 涂远茂 李辉 邱丹丹 王晶晶 左科 程震 刘志红 CHEN Duqun;TU Yuanmao;LI Hui;QIU Dandan;WANG Jingjing;ZUO Ke;CHENG Zhen;LIU Zhihong(National Clinical Research Center for Kidney Diseases,Jinling Hospital,Nanjing 210016,China)

机构地区：[1]东部战区总医院国家肾脏疾病临床医学研究中心,南京210016

出　　处：《肾脏病与透析肾移植杂志》2025年第1期1-7,共7页Chinese Journal of Nephrology,Dialysis & Transplantation

基　　金：江苏省卫健委医学科研面上项目(H2023017);临床诊疗新技术(22LCZLXJS7)。

摘　　要：目的:回顾性观察奥妥珠单抗(OBZ)治疗难治及高危磷脂酶A2受体(PLA2R)相关膜性肾病(MN)的疗效和安全性。方法:分析2022年9月至2023年12月于国家肾脏疾病临床医学研究中心接受OBZ治疗的PLA2R相关MN患者的临床病理、随访资料。高危的定义依据全球改善肾脏预后组织(KDIGO)指南及专家共识。难治性MN定义为患者接受激素联合免疫抑制剂如钙调神经蛋白抑制剂、环磷酰胺或利妥昔单抗治疗半年以上未获得蛋白尿缓解(尿蛋白下降<50%且>3.5 g/24h)。结果:本研究纳入72例PLA2R相关MN患者,其中56例为难治,16例为未接受免疫抑制治疗的高危患者。基线尿蛋白定量为10.2 g/24h。第12月时70例(97%)患者达到缓解,达到缓解的中位时间为3(3~6)月。其中24例(33%)获得完全缓解(CR)。高危、难治患者第12个月缓解率分别为100%、96%,CR率分别为56%、27%。高危患者CR率显著高于难治患者(HR=2.497,95%CI 1.041~5.989)。6周起尿蛋白显著下降,血清白蛋白、估算的肾小球滤过率(eGFR)显著升高。所有患者前3个月均维持B细胞耗竭,B细胞重建(CD20≥5个/μL)的中位时间为9(8~12)月。67例患者基线抗PLA2R抗体(aPLA2Rab)≥14 RU/mL,6月、12月免疫学完全缓解率(aPLA2Rab<2 RU/mL)分别为87%、99%。轻中度输液反应发生率28%,2例(2.8%)患者出现肺部感染,无患者死亡或进展为终末期肾病。结论:OBZ治疗高危及难治PLA2R相关MN均安全、有效。B细胞耗竭时间长,免疫学缓解率高,临床缓解快,值得进一步开展大规模、前瞻性研究。Objective:To investigate to the efficacy and safety of obinutuzumab in the treatment of high risk or refractory phospholipase A2 receptor associated membranous nephropathy.Methodology:Patients with biopsy-proven MN or serum anti-phospholipase A2 receptor antibody(aPLA2Rab)titers≥14 RU/ml treated with obinutuzumab(1 g×2)in the National Clinical Medical Research Center for Renal Diseases at Jinling Hospital from September 2022 to December 2023 were retrospectively analyzed.High risk was classified according to kidney disease:Improving Global Outcomes guideline and expert recommendation.Refractory disease was termed as patients received immunosuppressive agents such as cyclophosphamide,calcineurin inhibitors or Rituximab with or without steroids for more than 6 months but have not yet achieved remission(proteinuria decline<50%and>3.5 g/24h).Results:Our analysis included 72 patients(56 refractory,16 high risk MN),baseline proteinuria was 10.2 g/24h.70(97%)patients achieved remission at month 12,including 24(33%)achieved complete remission(CR).The median time to remission was 3(3~6)months.Remission rate,CR rate of high risk and refractory MN was 100%and 96%,56%and 27%respectively.CR rate was significantly high in high-risk group than refractory group(HR=2.497,95%CI 1.041~5.989).Obinutuzumab significantly reduced 24-hour proteinuria and increased serum albumin,estimated glomerular filtration rate since week 6.Complete depletion of circulating B cell was maintained in all patients within 3 months and the median time to B cell reconstitution(CD20+cells≥5/μL)was 9(8~12)months.67 patients presented with serum aPLA2Rab≥14 RU/mL at baseline and complete immunological remission(aPLA2Rab<2 RU/mL)was achieved in 87%and 99%at month 6 and 12 respectively.Infusion-related adverse event was revealed in 28%patients and mostly mild.Pulmonary infections occurred in 2(2.8%)patients.No patients died or progression into end stage kidney disease.Conclusion:Obinutuzumab is a promising treatment option for both high risk and refract

关 键 词：膜性肾病 奥妥珠单抗 磷脂酶A2受体 高危 难治 

分 类 号：R692[医药卫生—泌尿科学]