利妥昔单克隆抗体不宜作为继发性难治性肾病的挽救治疗措施  

Rituximab Salvage Therapy Is Inappropriate for Secondary Refractory Nephropathy

作　　者：张东亮[1] 罗莉 郑力仁 胡娜娜 万利 杨清华 张周沧[1] ZHANG Dongliang;LUO Li;ZHENG Liren;HU Nana;WAN Li;YANG Qinghua;ZHANG Zhoucang(Blood Purification Center of Nephrology Department,Peking University International Hospital,Beijing 102206,China)

机构地区：[1]北京大学国际医院肾内科部血液净化中心,北京市102206

出　　处：《中国全科医学》2020年第36期4645-4650,共6页Chinese General Practice

摘　　要：背景利妥昔单克隆抗体(RTX)用于肾小球疾病的治疗已近20年,近年来其在治疗原发性和继发性肾病方面积累了一些循证医学证据,但对于较为明显的肾功能不全患者是否适合应用RTX进行挽救性治疗,目前尚无相关研究。目的观察RTX挽救性治疗继发性难治性肾病患者的有效性和安全性。方法回顾性选取2018—2019年北京大学国际医院收治的所有住院使用RTX治疗的成年难治性肾病患者48例。根据原发病诊断结果将患者分为原发性肾病(PN)组和继发性肾病(SN)组,再将SN组依据RTX治疗前血肌酐(Scr)分为SN-NST亚组(Scr<300μmol/L)和SN-ST亚组(Scr≥300μmol/L)。收集所有患者的一般资料(包括性别、年龄、体质量、身高、体表面积、原发病),RTX治疗前、后实验室检查结果〔24 h尿蛋白(Upro)、白细胞计数(WBC)、红细胞计数(RBC)、血小板计数(PLT)、白蛋白(Alb)、Scr、CD4+细胞计数〕,计算CD4+细胞计数/WBC比例,记录RTX治疗期间严重不良事件〔包括严重感染全身(应用抗生素≥7 d或联合应用2种及以上抗感染药物)、肾脏替代治疗(RRT)、多脏器功能衰竭综合征(MODS)、死亡等〕,RTX末次治疗后3个月肾脏转归情况(即是否行维持性血液透析)。结果48例使用RTX治疗的难治性肾病患者均进行肾穿刺活检;PN组19例(39.6%),SN-NST亚组14例(29.2%),SN-ST亚组15例(31.2%)。SN-ST亚组患者年龄小于PN组和SN-NST亚组(P<0.05)。PN组患者RTX治疗前24 hUpro、RBC、PLT高于SN-NST亚组、SN-ST亚组,Alb低于SN-NST亚组、SN-ST亚组(P<0.05);SN-ST亚组患者RTX治疗前Scr高于PN组、SN-NST亚组,CD4+细胞计数低于PN组、SN-NST亚组(P<0.05)。SN-ST亚组患者RTX治疗后Scr高于PN组、SN-NST亚组(P<0.05)。PN组、SN-NST亚组患者RTX治疗后24 hUpro较同组治疗前降低(P<0.05)。SN-NST亚组、SN-ST亚组患者RTX治疗后WBC较同组治疗前降低(P<0.05)。SN-ST亚组患者RTX治疗后RBC较同组治疗前升高(P<0.05)。PN�Background Rituximab(RTX) has been used to treat glomerular diseases for nearly 20 years.Although there have been accumulated results from evidence-based studies of RTX for primary and secondary nephropathy,there is no research on RTX salvage therapy for severe renal insufficiency.Objective To study the efficacy and safety of RTX salvage therapy in patients with secondary refractory nephropathy.Methods Total 48 adult inpatients with refractory nephropathy,who received RTX treatment in Peking University International Hospital from 2018 to 2019,were enrolled in this retrospective study.They were divided into primary nephropathy(PN) group and secondary nephropathy(SN) group according to renal biopsy diagnosis of primary disease.Those in SN group were further divided into SN with non-salvage therapy group(SN-NST subgroup,Scr<300 μmol/L) and SN with salvage therapy group(SN-ST subgroup,Scr ≥ 300 μmol/L) according to the Scr level before RTX treatment.General information(including gender,age,weight,height,body surface area and primary diagnosis),and laboratory tests results before and after using RTX,such as 24-hour urine protein(Upro),white blood cell(WBC) count,red blood cell(RBC) count,platelet(PLT) count,serum albumin(Alb),Scr,and CD4+ cell count as well as calculated CD4+ cell count/WBC ratio were collected.The serious adverse events during RTX treatment 〔including serious infection(treated either by 7 or more days of systemic antibiotic therapy or by more than one antibiotic agents),renal replacement therapy,multiple organ dysfunction syndrome,and death〕,were recorded.3-month renal outcome after the final RTX therapy(namely,whether requiring maintenance hemdialysis) was also recorded.Results There were 19(39.6%) patients in PN group,14(29.2%)in SN-NST subgroup,and 15(31.2%)in SN-ST subgroup.The mean age of SN-ST subgroup was less than that of PN group and SN-NST subgroup(P<0.05).PN group showed higher mean baseline levels of 24 hUpro,RBC and PLT,and lower mean Alb than both subgroups SN-NST and SN-ST befo

关 键 词：肾病 利妥昔单克隆抗体 继发性肾小球肾炎 挽救治疗 预后 感染 药物毒性 

分 类 号：R692[医药卫生—泌尿科学]