摘要
目的:探讨极低剂量利妥昔单抗治疗难治性膜性肾病的临床疗效和安全性。方法:收集2020至2022年期间26例诊断为难治性膜性肾病患者为观察对象,在原有治疗方案的基础上接受极低剂量利妥昔单抗(0.1 g/周静脉注射)治疗。于治疗1周后、2周后、3月和6个月后复查随访,比较极低剂量利妥昔单抗治疗前后的肾功能、肝功能、24 h尿蛋白定量、血浆白蛋白、免疫球蛋白水平、血清磷脂酶A2(PLA2R)受体抗体、外周血CD19+B细胞和CD20+B细胞的水平,分析极低剂量利妥昔单抗治疗难治性膜性肾病的有效性和安全性。结果:26例难治性膜性肾病患者,男性17例(65.4%),女性9例(34.6%),平均年龄(43.3±18.1)岁,平均膜性肾病病史(63.6±81.6)月。26例随访超过6个月,17例(65.4%)获得完全缓解、7例(26.9%)部分缓解和2例(7.7%)治疗无效。采用极低剂量利妥昔单抗治疗后患者血清白蛋白水平从24.1 g/L逐渐升高至35.4 g/L(均P<0.05),24 h尿蛋白水平从6.862 g逐渐降低至1.509 g,血清PLA2R从0.625(0.000,0.781)mg/L逐渐降低至0.000(0.000,0.019)mg/L(均P<0.05),血清肌酐水平和肾小球滤过率无明显变化。随访中CD19+B细胞计数[基线:257.3(157.0,395.1)/mm^(3);6月:2.78(1.06,3.96)/mm^(3);P<0.05]和CD20+阳性B细胞计数[基线:252.6(150.6,388.9)/mm^(3);6月:1.80(0.58,4.83)/mm^(3);P<0.001]较治疗前显著下降。在治疗过程中仅1例出现肺部感染和1例出现恶心呕吐的不良事件。结论:本研究证实在原有治疗的基础上加用极低剂量利妥昔单抗治疗难治性膜性肾病相对安全、有效、经济,但仍然需要大样本量的多中心随机临床试验探讨极低剂量利妥昔单抗和常规剂量利妥昔单抗治疗难治性膜性肾病的疗效差异。
Objective:The effectiveness and safety of ultra-low dose rituximab in treating refractory membranous nephropathy were investigated.Methods:Patients diagnosed with refractory membranous nephropathy received ultra-low dose rituximab(0.1 g/week intravenous injection)in addition to their original treatment plan.Patients were scheduled for follow-up visits after 1 week,2 weeks,3 months,and 6 months of treatment.We compared renal function,24-hour urine protein,serum albumin,liver function,immunoglobulin,peripheral blood CD19+B cell,and CD20+B cell levels before and after treatment with ultra-low dose rituximab.The efficacy and safety of ultra-low dose rituximab in treating refractory membranous nephropathy were analyzed.Results:A total of 26 patients with refractory membranous nephropathy were treated with ultra-low dose rituximab,with 17 male patients(65.4%)and 9 female patients(34.6%),with a mean age of(43.3±18.1)years and a mean history of membranous nephropathy of(63.6±81.6)months.During follow-up,17 patients(65.4%)achieved complete remission,7 patients(26.9%)achieved partial response,and 2 patients(7.7%)were ineffective.After treatment with ultra-low dose rituximab,serum albumin levels gradually increased from 24.1 to 35.4 g/L,24-hour urine protein levels gradually decreased from 6.862 g to 1.509 g,and serum PLA2R levels gradually decreased from 0.625(0.000,0.781)mg/L to 0.000(0.000,0.019)mg/L(P<0.05),while serum creatinine levels and glomerular filtration rates did not significantly change.During the follow-up,the levels of CD19+B cell counts[baseline:257.3(157.0,395.1)/mm^(3);6 months:2.78(1.06,3.96)/mm^(3);P<0.05]and CD20+B cell counts[baseline:252.6(150.6,388.9)/mm^(3);6 months:1.80(0.58,4.83)/mm^(3) P<0.001]were significantly lower than those before treatment.During treatment,only one patient had a pulmonary infection and one patient experienced adverse events of nausea and vomiting.Conclusion:Adding ultra-low dose rituximab to the original treatment plan is relatively safe,effective,and economical in treating refractory membranous nephropathy.However,multicenter randomized clinical trials with larger sample sizes are needed to investigate the difference in efficacy between ultra-low dose rituximab and conventional-dose rituximab in treating refractory membranous nephropathy.
作者
李国萍
季大玺
秦影
刘丽
谢红燕
唐政
LI Guoping;JI Daxi;QIN Ying;LIU Li;XIE Hongyan;TANG Zheng(Department of Nephrology,Nanjing Yimin Hospital,Nanjing 211100,Jiangsu,China;National Clinical Research Center of Kidney Diseases,Jingling Hospital,Nanjing University School of Medicine,Nanjing 210016,Jiangsu,China)
出处
《暨南大学学报（自然科学与医学版）》
CAS
北大核心
2023年第1期37-45,共9页
Journal of Jinan University(Natural Science & Medicine Edition)
