个体化利妥昔单抗挽救治疗伴急性肾损伤的活动性狼疮肾炎的疗效分析

Efficacy of individualized rituximab as the rescue therapy for active lupus nephritis with acute kidney injury

目的探讨个体化的利妥昔单抗(rituximab,RTX)挽救治疗对于伴急性肾损伤(acute kidney injury,AKI)的活动性狼疮肾炎(lupus nephritis,LN)的疗效和安全性。方法回顾性收集2017年4月至2020年6月于浙江大学医学院附属第一医院肾脏病中心住院的合并AKI并使用RTX治疗的LN患者资料,分析RTX治疗后的肾脏缓解率与不良反应。使用Kaplan-Meier法计算患者缓解情况的累积发生率。结果共纳入13例患者,其中女性8例;年龄(35.23±15.92)岁。RTX治疗前尿蛋白/肌酐比值为(5.22±1.57)g/g,4例患者入院时为透析治疗,9例未透析患者血清肌酐为(223.22±85.73)μmol/L。8例患者经肾活检病理证实为增殖性LN,其中7例有新月体形成,1例合并血栓性微血管病(thrombotic microangiopathy,TMA);另5例未行肾活检,临床诊断为TMA。患者使用RTX的剂量为(815±516)mg(200~2100 mg),均达到外周血B细胞清除状态(外周血CD19+B细胞计数<5个/μl),首次RTX治疗后达到B细胞清除的中位时间为21(15,35)d,其中8例患者达到B细胞耗竭(外周血CD19+B细胞计数为0)。患者的缓解率为12/13(2例完全缓解,10例部分缓解),其中3例脱离透析;1例(肾小球硬化比例52.94%)进入维持透析。7例难治性LN患者在使用RTX治疗后的维持缓解期复发次数从(1.57±0.53)次[随访时间60(20,109)个月]下降至(0.43±0.79)次[随访时间18(10,23)个月](P=0.015)。使用RTX后,患者的感染发生率为7/13,出现感染的中位时间为26(4,44)d,肺部感染(5/13)最常见,经抗感染治疗后均痊愈。结论RTX可用于治疗伴AKI的活动性LN患者,尤其是新月体形成和TMA表现者,但需预防和关注患者的感染情况。

Objective To investigate the efficacy and safety of individualized rituximab rescue therapy for active lupus nephritis with acute kidney injury(AKI).Methods The clinical data of lupus nephritis patients with AKI treated with rituximab at the Kidney Disease Center of the First Affiliated Hospital of Zhejiang University School of Medicine from April 2017 to June 2020 were collected,and the renal remission rate and adverse events after rituximab treatment were analyzed retrospectively.The Kaplan-Meier method was used to calculate the cumulative incidence of patients'remission.Results There were 13 patients enrolled,including 8 females,and aged(35.23±15.92)years old.The urinary protein/creatinine ratio was(5.22±1.57)g/g before rituximab treatment.Four patients were on dialysis at admission,and 9 patients without dialysis had serum creatinine of(223.22±85.73)μmol/L.Eight patients were confirmed as proliferative lupus nephritis by renal biopsies,including 7 cases with crescent formation and 1 case with thrombotic microangiopathy(TMA),and the other 5 cases without renal biopsies were clinically diagnosed as TMA.The dose of rituximab was(815±516)mg(200-2100 mg),and all the patients reached the state of peripheral blood B cells clearance(CD19+B cell count was<5/μl).After the first treatment of rituximab,the median time to B-cell clearance was 21(15,35)days,and 8 patients reached B-cell depletion(CD19+B cell count was 0).The remission rate was 12/13(two cases reached complete remission,and 10 cases reached partial remission).Three cases stopped dialysis,and 1 case(with glomerulosclerosis of 52.94%)entered maintaining dialysis.The relapse times in the maintenance remission period of 7 patients with refractory lupus nephritis declined significantly from(1.57±0.53)times in a median history of 60(20,109)months to(0.43±0.79)times in a median history of 18(10,23)months after the use of rituximab(P=0.015).After using rituximab,the incidence of infection was 7/13.The median time from the use of rituximab to infection was 26(4,44)days.Pulmonary infection(5/13)was the most common type and all infected patients recovered after anti-infection treatment.Conclusions Rituximab can be used in the treatment of active lupus nephritis with AKI,especially in patients with crescent formation and TMA,but the infection should be paid close attention to and prevented.