利妥昔单抗治疗成人微小病变型肾病的疗效及安全性研究

Study on the Efficacy and Safety of Rituximab in the Treatment of Adult Minimal Change Disease

摘要: 目的：探讨利妥昔单抗(Rituximab, RTX)治疗成人微小病变型肾病(Minimal Change Disease, MCD)的疗效及安全性。方法：回顾性分析于2020年01月至2024年02月就诊于青岛大学附属泰安市中心医院肾病科的成人MCD患者86例，根据治疗方案分为：初治组(n = 28)、难治组(n = 28)、对照组(n = 30)，初治组应用RTX治疗，难治组在频繁复发/激素依赖后应用RTX治疗，对照组应用激素泼尼松单药治疗。分析三组患者生化指标、缓解率、复发率及不良事件发生率。结果：治疗后三组患者的24小时尿蛋白定量(24h-UTP)显著下降，血清白蛋白显著上升，血肌酐下降并逐渐趋于平稳，且初治组、难治组的生化指标均优于对照组。初治组及难治组患者应用RTX治疗4周后CD19⁺ B淋巴细胞呈现耗竭状态，耗竭状态可持续12~24周，24周后逐渐出现恢复，48周时CD19⁺ B淋巴细胞数接近基线水平，在末次随访时初治组较难治组CD19⁺ B淋巴细胞数量少(P < 0.05)。初治组及难治组应用RTX治疗可有效减少激素、免疫抑制剂的用时、用量。初治组及难治组的缓解率均显著高于对照组(P < 0.05)，在48周时对照组仅有53.3%的患者达到缓解，复发率高达36.7%；初治组较难治组的缓解率高、复发率低，有统计学差异(P < 0.05)。对照组不良事件发生率高达40%，显著高于初治组及难治组(P < 0.05)。结论：RTX治疗成人MCD较激素单药治疗缓解率高、复发率低、不良反应少，且有效减少了激素/免疫抑制剂的用时、用量。

Abstract: Objective: To investigate the efficacy and safety of rituximab in treating adult minimal change disease. Methods: A retrospective analysis was conducted on 86 adult MCD patients who visited the Nephrology Department of Tai’an Central Hospital affiliated to Qingdao University from January 2020 to February 2024. According to the treatment plan, they were divided into three groups: initial treatment group (n = 28), refractory group (n = 28), and control group (n = 30). The initial treatment group received RTX treatment, the refractory group received RTX treatment after frequent recurrence/hormone dependence, and the control group received prednisone monotherapy. We analyze the biochemical indicators, remission rate, recurrence rate, and incidence of adverse events in three groups of patients. Result: After treatment, the 24-hour urinary protein quantification (24h-UTP) of the three groups of patients significantly decreased, serum albumin significantly increased, blood creatinine decreased and gradually stabilized, and the biochemical indicators of the initial treatment group and refractory group were better than those of the control group. After 4 weeks of RTX treatment, the CD19⁺ B lymphocyte count in both the initial treatment group and the refractory group showed a depletion state, which lasted for 12~24 weeks. After 24 weeks, there was a gradual recovery, and at 48 weeks, the CD19⁺ B lymphocyte count was close to baseline. At the last follow-up, the CD19⁺ B lymphocyte count in the initial treatment group was lower than that in the refractory group (P < 0.05). The use of RTX therapy in the initial treatment group and refractory group can effectively reduce the time and dosage of hormones and immunosuppressants. The remission rates of the initial treatment group and the refractory group were significantly higher than the control group (P < 0.05). At 48 weeks, only 53.3% of patients in the control group achieved remission, and the recurrence rate was as high as 36.7%. The remission rate and recurrence rate of the initial treatment group were higher and lower than those of the refractory group, with statistical differences (P < 0.05). The incidence of adverse events in the control group was as high as 40%, significantly higher than that in the initial treatment group and the refractory group (P < 0.05). Conclusion: RTX treatment of adult MCD has a high remission rate, low recurrence rate and fewer adverse reactions than that of hormone single drug therapy, and treatment can effectively reduce the duration and dosage of hormones/immunosuppressants.