咪唑立宾与吗替麦考酚酯在肾移植受者中的疗效及安全性比较：一项单中心回顾性研究

Comparison of efficacy and safety of mizoribine and mycophenolate mofetil in kidney transplant recipients: a single-center retrospective study

摘要

目的 比较肾移植受者采用咪唑立宾（MZR）或吗替麦考酚酯（MMF）联合他克莫司（Tac）及糖皮质激素的三联免疫抑制方案在术后1年的临床疗效与安全性差异。方法 采用单中心回顾性队列研究设计，纳入北京大学第三医院在2022年1月至2024年12月首次接受同种异体肾移植的156例患者的临床资料。根据术后初始免疫抑制方案分为MZR组（78例）与MMF组（78例）。比较两组受者的基线资料、术后1年用药情况、血常规等指标、不良事件与临床结局。对于重复测量的纵向数据，采用重复测量方差分析，评估指标的组间主效应、时间主效应及其交互效应。结果 在主要疗效终点上，两组受者术后1年生存率、移植物存活率及急性排斥反应发生率差异均无统计学意义（均为 P>0.05）。在用药模式及实验室检查指标上，Tac剂量存在时间主效应和“时间×组别”交互效应（均为 P<0.05），术后2~3个月MZR组Tac剂量低于MMF组，术后7~12个月、术后1年后MZR组Tac剂量均高于MMF组，MZR组术后1个月后的白细胞计数均高于MMF组，且术后1年后血小板计数更高（均为 P<0.05）。感染方面，MZR组新型冠状病毒及耶氏肺孢子菌肺炎感染发生率均更低（均为 P<0.05）。在代谢指标上，MZR组术后尿酸水平优于MMF组，但其术后1年后总胆固醇水平较高（均为 P<0.05）。肝功能方面，MZR组术后早期转氨酶有短暂轻度升高。结论 术后为期1年的随访中，MZR与MMF方案在中国肾移植受者中展现出相当的免疫抑制疗效与总体安全性。MZR方案在减少特定感染风险、减轻骨髓抑制以及改善尿酸代谢方面显示出明确优势，但其对血脂的潜在影响需予以关注。因此，MZR可作为肾移植受者，尤其是高感染风险、血液系统耐受性差或合并高尿酸血症受者的有效且安全的替代免疫抑制选择。

Abstract

Objective To compare the clinical efficacy and safety differences between the triple immunosuppressive regimen of mizoribine (MZR) or mycophenolate mofetil (MMF) combined with tacrolimus (Tac) and glucocorticoids of kidney transplant recipients in one year after transplantation. Methods A single-center retrospective cohort study design was adopted. The clinical data of 156 patients who underwent the first allogeneic kidney transplantation at the Third Hospital of Peking University from January 2022 to December 2024 were included. The patients were divided into the MZR group (78 cases) and the MMF group (78 cases) based on the initial immunosuppressive regimen after transplantation. The baseline data, medication use in one year after transplantation, blood routine indicators, adverse events and clinical outcomes were compared between the two groups. For the repeated-measurement longitudinal data, repeated-measurement analysis of variance was used to evaluate the main effects of the groups, time and their interaction effects. Results At the primary efficacy endpoint, there were no statistically significant differences in the one-year survival rate, graft survival rate and incidence of acute rejection between the two groups (all P > 0.05). In terms of medication patterns and laboratory test indicators, there were significant time main effects and "time × group" interaction effects for Tac dosage (all P < 0.05). The Tac dosage in the MZR group was lower than that in the MMF group from 2 to 3 months after transplantation, and it was higher in the MZR group than in the MMF group from 7 to 12 months and one year after transplantation. White blood cell count in the MZR group was higher at one month after transplantation, and the platelet count was higher one year after transplantation (all P < 0.05). In terms of infection, the incidence of novel coronavirus and Pneumocystis jirovecii pneumonia infections in the MZR group was lower (all P < 0.05). In terms of metabolic indicators, the post-transplantation uric acid level was better in the MZR group than in the MMF group, but the total cholesterol level was higher one year after transplantation (all P < 0.05). In terms of liver function, there was a brief and mild increase in transaminase in the early stage after transplantation in the MZR group. Conclusions During the one-year follow-up after transplantation, both the MZR and MMF regimens demonstrate comparable immunosuppressive efficacy and overall safety in Chinese kidney transplant recipients. The MZR regimen shows clear advantages in reducing specific infection risks, alleviating bone marrow suppression and improving uric acid metabolism, but its potential impact on blood lipids needs to be monitored. Therefore, the MZR regimen may be an effective and safe alternative immunosuppressive option for kidney transplant recipients, especially those with high infection risk, poor hematological tolerance, or comorbid hyperuricemia.

关键词

肾移植 / 咪唑立宾 / 吗替麦考酚酯 / 他克莫司 / 用药剂量 / 疗效 / 安全性 / 估算肾小球滤过率

Key words

Kidney transplantation / Mizoribine / Mycophenolate mofetil / Tacrolimus / Dosage / Efficacy / Safety / Estimated glomerular filtration rate

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基金资助

国家自然科学基金(72304007)

吴阶平医学基金会临床科研专项资助基金(320.6750.2022-03-45)