不同剂量咪唑立宾在临床肾移植中的应用研究

Application of various doses of mizoribine in clinical kidney transplantation

目的探讨不同剂量咪唑立宾（MzR）在临床肾移植中的应用效果及其安全性。方法将206例首次接受肾移植的受者按手术时间排序，以奇偶数将受者列入吗替麦考酚酯（MMF）组，MZRI组和MZRII组。MMF组受者术后采用MMF＋环孢素A（CsA）＋泼尼松（Pred）的免疫抑制方案，MZRI组和MZRⅡ组采用MZR＋CsA＋Pred的免疫抑制方案；MMF组MMF的用量为1．0g／d，MZRI组和MZRII组MZR的用量分别为100和200mg／d，3组间CsA和Pred的用法相同。排除失随访受者，MMF组、MZRI组和MZRⅡ组分别有100、60和30例受者获得完整随访，研究终点为肾移植术后5年。比较各组受者人、肾存活率和排斥反应发生率，以及与药物相关不良反应的发生情况等。结果MZRI组、MZRⅡ组和MMF组受者术后总体存活率分别为88．3％（53／60）、90％（27／30）和88％（88／100），移植肾总体存活率分别为85％（51／60）、86．7％（26／30）和86％（86／1OO），急性排斥反应发生率分别为10％（6／60）、6．7％（2／30）和9％（9／100），3组间人、肾存活率以及急性排斥反应发生率的差异均无统计学意义（P〉0．05）；严重肺部感染发生率分别为3．3％（2／60）、10％（3／30）和15％（15／100），MZRI组显著低于MMF组（Pd0．05），而MZRⅡ组与其他两组的差异均无统计学意义（P〉O．05）。MZRI组和MZRⅡ组发生严重感染者均经治疗后痊愈，而MMF组死亡11例，死亡率为73．3％（11／15）。MZRI组和MZRⅡ组腹泻发生率均显著低于MMF组（P〈0．05），而高尿酸血症发生率均显著高于MMF组（P〈0．05）。结论咪唑立宾对预防肾移植后排斥反应是安全、有效的，受者耐受性好，对于免疫功能低下易发生感染的高危人群，以及使用MMF致顽固性腹泻者，可将含咪唑立宾的免疫抑制方案作为首选。

Objective To observe the efficacy and safety of different doses of mizoribine to prevent rejection after renal transplantation. Methods Sorted by time of operation and odevity, 206 primary kidney transplant recipients were divided into 3 groups, including MMF group, MZR I group and MZR Ⅱ group. All recipients in 3 groups were administrated CsA and Pred, combined with mycophenolate mofitile （MMF） in MMF group and mizoribine （MMF） in MZR Ⅰ and Ⅱ groups. The dosage of MMF was 1.0 g/day, while dosage of MZR in MZR I and Ⅱ groups was 100 and 200 mg/day, respectively. There was no difference in usage of cyclosporine （CsA） and prednisone （Pred） among 3 groups. 100, 60 and 30 recipients were followed up in MMF, MZR I and MZR II groups respectively in 5 years. During the follow-up period of 5 years, the incidence of acute rejection, patient/graft survival and adverse effects associated with drugs in three groups were observed. Resdts The patient/graft survival was 88. 3 % （53/60）, 85 % （51/60） in MZR I group, 90 % （27/30）, 86.7% （26/30） in MZR II group, and 88% （88/100）, 86% （86/100） in MMF group, respectively （P〉0. 05）. There was no significant difference in incidence of acute rejection among MZR I （10 %, 6/60）, MZR Ⅱ （6. 7 %, 2/30） and MMF groups （9 %, 9/100）. The incidence of severe pulmonary infection in MZR I group was 3.3 % （2/60）, and 10 % （3/30） in MZR Ⅱ , and the former was lower than MMF group （15%, 15/100） significantly. There was significant difference in mortality of severe pulmonary infection between MZR I group （0, 0/2） and MMT group （73.3%, 11/15）. The rate of ACR in MZR Ⅱ group （10%, 3/30） was lower significantly than MMF group （30%, 30/100） and MZR I group （31.7 %, 19/60）. There was significant difference in the incidence of hyperuricaeidemia between two MZR groups （30%, 56.7%） and MMF group （10%） （P〈0. 05）, while the incidence of diarrhea and myelosuppression was lower significantly in MZR I group than in MMF group. Conclusion MZR can prevent acute rejection after kidney transplantation effectively and safely. Immunosuppressive therapy including mizoribine is the best choice especially for high risk group because of susceptibility to infection and those who suffer from tenacious diarrhea owing to the side effect.