利妥昔单抗治疗成人原发性局灶性节段性肾小球硬化症的临床分析

Rituximab therapy for adult patients with idiopathic focal segmental glomerulosclerosis

目的评价利妥昔单抗治疗成人原发性局灶性节段性肾小球硬化症(focal segmental glomerulosclerosis,FSGS)的疗效和安全性。方法回顾性分析浙江大学医学院附属第一医院收治的原发性FSGS且接受过利妥昔单抗治疗患者的临床资料。入选者接受利妥昔单抗治疗1次或2次,单次剂量为375 mg/m2,2次用药间隔时间为2周。治疗达标指标为达到B细胞清除状态(外周血B细胞计数<5个/μl)。随访主要观察指标为肾病的缓解与复发情况,次要观察指标为不良事件和肾脏结局。结果共纳入14例FSGS患者,男性9例,其中7例为激素依赖型或频繁复发型肾病综合征,6例为激素耐药型肾病综合征,1例初发肾病综合征患者存在激素应用禁忌。利妥昔单抗治疗后,7例激素依赖型/频繁复发型肾病综合征患者获完全缓解,随访6个月时激素用量较基线值显著减少[(33.3±5.2)mg/d比(6.7±6.6)mg/d,P<0.01];除1例患者联合应用他克莫司(1.0 mg/d),其余患者均停用免疫抑制剂;总复发次数/总随访月由治疗前0.257次/月降至治疗后0.058次/月。其他6例激素耐药型肾病综合征和1例有激素应用禁忌的患者中,4例于治疗后34.50(20.25,95.25)d缓解,其中3例激素耐药型肾病综合征患者获部分缓解,1例初发患者获完全缓解;3例未缓解,其中1例患者在随访23个月时进展至终末期肾病。结论利妥昔单抗治疗成人激素依赖型/频繁复发型FSGS可降低复发风险,并有助于减少激素和免疫抑制剂的用量或停用,但对激素耐药型FSGS的临床疗效不佳.

Objective To evaluate the efficacy and safety of rituximab in the treatment of adult primary focal segmental glomerulosclerosis(FSGS).Methods Adult FSGS patients treated with rituximab in the First Affiliated Hospital of Zhejiang University College of Medicine were retrospectively enrolled.One or two doses of rituximab(375 mg/m2)were used aiming to achieve B cell depletion(defined as<5 B cells per microliter in peripheral blood)and the interval between the two doses was 2 weeks.The evaluated major outcomes were remission and relapse of nephropathy,and the secondary outcome measures were adverse events and renal outcomes.Results A total of 14 patients(9 males)were enrolled,among whom 7 cases were steroid-dependent nephrotic syndrome(SDNS)or frequently relapsing nephrotic syndrome(FRNS),6 cases were steroid-resistant nephrotic syndrome(SRNS)and one patient was new onset FSGS with contraindication to steroid.After treatment with rituximab,7 patients with SDNS/FRNS achieved complete remission.At 6 months,the daily oral steroid dose reduced significantly compared with the baseline[(33.3±5.2)mg/d vs(6.7±6.6)mg/d,P<0.01];while one patient still received tacrolimus 1.0 mg/d,the other 6 patients stopped using immunosuppressants;and the total number of relapse/total follow-up months decreased from 0.257 times/month to 0.058 times/month after the use of rituximab.For the other 6 SRNS patients and one patient with contraindication to steroid,three SRNS patients achieved partial remission and one patient with contraindication to steroid achieved complete remission at 34.50(20.25,95.25)days after use of rituximab,and the other 3 SRNS patients failed to achieve remission,of whom one patient developed end stage renal disease at 23 months.Conclusions Rituximab may reduce the risk of relapse and help steroid or immunosuppressant-tapering in adult steroid-dependent/frequently relapsing idiopathic FSGS.However,it is not effective in SRNS patients.