不同剂量利妥昔单抗治疗特发性膜性肾病的有效性和安全性  

Efficacy and safety of two dose regimens of rituximab for idiopathic membranous nephropathy

作　　者：涂志辉 杨定平[1] Tu Zhi-hui;Yang Ding-ping(Department of Nephrology,Renmin Hospital of Wuhan University,Wuhan 430060,China)

机构地区：[1]武汉大学人民医院肾内科,武汉430060

出　　处：《临床肾脏病杂志》2024年第2期89-95,共7页Journal Of Clinical Nephrology

基　　金：国家自然科学基金面上项目(81670631);国家重点研发计划(2018YFC1311300)。

摘　　要：目的对比两种不同剂量利妥昔单抗方案治疗特发性膜性肾病患者的临床疗效。方法选取2019年12月1日至2021年12月31日经武汉大学人民医院诊断为特发性膜性肾病的患者,共79例。利妥昔单抗两剂方案组(49例):1 g/次,第1、15天各用1次,如随访6个月时仍有肾病范围的蛋白尿,重复该方案1次;利妥昔单抗四剂方案组(30例):375 mg/m^(2),每周1次,共4次;2组均联合小剂量糖皮质激素。对比两组患者在治疗前后不同时间的24 h尿蛋白定量、血清白蛋白、血肌酐、外周血CD19^(+)细胞计数、抗PLA2R抗体滴度、疾病缓解率、不良反应等方面的差异。结果2组患者治疗前在性别、年龄、体重指数、血压、24 h尿蛋白定量、血清白蛋白、血肌酐、估算肾小球滤过率、抗PLA2R抗体、外周血CD19^(+)细胞计数等方面,差异均无统计学意义(P>0.05)。12个月后,2组24 h尿蛋白定量较治疗前均有显著下降(P<0.01),血清白蛋白水平较治疗前均明显有所升高[两剂方案组:(25.34±4.64)g/L比(37.33±8.33)g/L,四剂方案组:(22.76±4.62)g/L比(35.47±5.90)g/L,P<0.01]。然而,治疗后降低尿蛋白和恢复血清白蛋白方面,2组比较差异无统计学意义(P>0.05)。在血肌酐方面,2组患者总体肾功能均能保持稳定,差异无统计学意义(P>0.05)。2组抗PLA2R-Ab水平治疗后较治疗前均能有效降低,且差异无统计学意义(P>0.05)。在疾病缓解方面,在12个月时总有效率达到75.95%,而两剂方案组的临床缓解率(85.71%)显然高于四剂方案组(60%),差异有统计学意义(P<0.01)。同时,两剂方案组的复发率(18.37%)不高于四剂方案组(23.33%)。在不良反应方面,两组比较差异无统计学意义(P>0.05)。结论较高剂量的利妥昔单抗方案的临床缓解率更高,同时不良反应发生率并没有增加,更适用于IMN的治疗,但药物可能引起严重低钾血症的不良反应仍然需要重视。Objective To compare the clinical efficacy and safety of two regimens of rituximab(RTX)for idiopathic membranous nephropathy(IMN).Methods A total of 79 IMN patients were recruited from December 01,2019 to December 31,2021.RTX two-dose regimen group(n=49):two infusions of 1g at 2-week intervals;if nephrotic albuminuria persisted during a 6-month follow-up,the regimen could be repeated once.RTX four-dose regimen group(n=30):four infusions of 375 mg/m^(2) at 1-week intervals.Both groups had a combination of low-dose glucocorticoid.The differences of 24-hour urinary protein,serum albumin,blood creatinine,peripheral blood CD19+cell count,anti-PLA2R antibody titer,disease remission rate and adverse reactions were compared between two groups before and at different timepoints post-treatment.Results No significant inter-group differences existed in gender,age,body mass index,blood pressure,24-hour urinary protein,serum albumin,blood creatinine,eGFR,anti-PLA2R antibody or peripheral blood CD19^(+) cell count pre-treatment(P>0.05).At Month 12,24-hour urinary protein declined markedly in 2 groups as compared with pre-treatment(P<0.01);serum level of albumin spiked markedly as compared with pre-treatment(P<0.01).However,no significant inter-group difference existed in reduction of urinary protein and recovery of serum albumin post-treatment(P>0.05).In terms of serum creatinine,total renal function of 2 groups remained stable without statistical significance(P>0.05).Anti-PLA2R-Ab level declined markedly in two groups post-treatment as compared with pre-treatment and the difference was not statistically significant(P>0.05).In terms of disease remission,total effective rate reached 75.95%at Month 12 and clinical remission rate of RTX two-dose regimen group was significantly higher than that of RTX four-dose regimen group(85.71%vs 60%).And the difference was statistically significant(P<0.01).Meanwhile,recurrence rate was lower in RTX two-dose group than that in RTX four-dose group(18.37%vs 23.33%).No significant inter-group diff

关 键 词：肾小球肾炎 膜性 抗CD20单抗 利妥昔单抗 不良反应 

分 类 号：R692[医药卫生—泌尿科学]