硼替佐米联合糖皮质激素治疗难治性狼疮性肾炎的近期疗效观察  

Treatment of bortezomib combined with glucocorticoids for refractory lupus nephritis

作　　者：章海涛[1] 刘正钊[1] 侯金花[1] 宋捷[1] 黄力[1] 黄湘华[1] 胡伟新[1] 刘志红[1] 

机构地区：[1]南京军区南京总医院肾脏科国家肾脏疾病临床医学研究中心全军肾脏病研究所,南京210016

出　　处：《肾脏病与透析肾移植杂志》2015年第6期501-506,共6页Chinese Journal of Nephrology,Dialysis & Transplantation

基　　金：国家科技支撑计划课题(2013BAI09B04;2015BAI12B05);江苏省临床医学科技专项(BL2012007)

摘　　要：目的:前瞻性观察硼替佐米联合糖皮质激素治疗难治性狼疮性肾炎(LN),评估其临床疗效及安全性。方法:观察2011年10月至2014年12月间难治性LN患者共5例,男性1例,女性4例,年龄21~43岁,Ⅳ型4例,Ⅴ+Ⅳ型1例。硼替佐米(1.3 mg/m^2,21d为一个治疗周期,每个周期第1、4、8、11天静脉推注)治疗4个周期,同时接受糖皮质激素治疗[甲泼尼龙(0.5 g/d)静脉滴注3d后口服泼尼松片治疗0.6 mg/(kg·d),4周后逐渐减量至10 mg/d维持]。观察硼替佐米治疗期间尿液检查、血清白蛋白、血清肌酐(SCr)、免疫学指标变化、不良事件及随访情况。结果:5例患者经过硼替佐米治疗2~4个周期治疗,4例患者获得部分缓解,SLE-DAI由12~16分降至4~8分,尿蛋白较治疗前减少,血清白蛋白上升,3例SCr异常者治疗后SCr较前下降,自身抗体滴度下降或转阴、补体升高。不良事件均为自身抗体滴度下降或转阴、补体升高。不良事件均为1~2级,包括一过性血小板减少、胃肠道症状、肢端麻木等,停药间期症状消失或改善。随访观察6~24个月,3例患者获得完全缓解,1例部分缓解,1例接受肾脏替代治疗。结论:硼替佐米联合糖皮质激素治疗可减少LN患者蛋白尿、改善肾功能,降低自身抗体滴度,不良事件多为轻~中度,治疗耐受性好。Objective：Refractory lupus nephritis （LN） is still a nodus for clinicians. The aim of this paper is to investigate the efficacy and safety of bortezomib combined with glucocorticoids for refractory lupus patients. Methodology：Five refractory lupus patients aged from 21 to 43 years （ femal 4 and male 1） with biopsy-proven （ classⅣ4 and classⅤ＋Ⅳ1） were recruited. They received bortezomib therapy for four cycles （1.3 mg/m^2 BSA, as an intravenous bolus on days 1, 4, 8, and 11 in a 21-day cycle） and glucocorticoids （ methylprednisolone 0-5 g/d intravenously for 3 days, followed by oral prednisone 0.6 mg/kg/d for 4 weeks and gradually tapered to 10 mg/d ） . The proteinuria, albumin, serum creatinine, immunological parameters and adverse effects were observed. Results：After 2～4 cycles of bortezomib treatment,4 patients received partial remission with SLE-DAI decreased from 12～16 to 4～8. Patients had a decline of proteinuria and elevated albumin after treatment. The SCr were decreased in 3 patients with abnormal SCr before therapy. The auto-antibodies and complements were also improved. The adverse events were grade 1～2,included transient thrombocytopenia, gastrointestinal symptom and acroanesthesia. Follow up 6～24 months, 3 patients received complete remission and 1 patient received partial remission. Only 1 patient received renal replacement therapy because of massive proteinuria and progressive renal function. Conclusion：Bortezomib combined with glucocorticoids can effectively reduce proteinuria,improve renal function and depress auto-antibodies with well tolerance and mild adverse events. It is may be an alternative therapy for LN treatment which needed deeply investigation.

关 键 词：狼疮性肾炎 硼替佐米 临床疗效 不良事件 

分 类 号：R593.242[医药卫生—内科学]