肾移植术后应用来氟米特的长期效果分析

目的 研究肾移植患者术后长期应用来氟米特（leflunomide,LEF）进行免疫抑制治疗的疗效和不良反应.方法 回顾性研究对象为2001年10月至2012年5月在第二军医大学附属长征医院长期随访（5年以上）的64例首次肾移植术后患者.应用钙神经蛋白抑制剂（CNI）＋LEF＋泼尼松三联免疫抑制方案的患者32例（LEF组）,应用CNI＋吗替麦考酚酯（MMF）＋泼尼松三联免疫抑制方案的患者32例（MMF组）.比较两组患者肾移植后1、3、5年人、肾存活率,肾功能变化、排斥反应、感染及不良反应的发生率.结果 LEF组与MMF组患者术后1、3、5年的人存活率分别为100%、97%、81%和100%、94%、88%;两组术后1、3、5年的肾存活率分别为97%、91%、75%和97%、91%、81%;两组之间比较差异无统计学意义（均为P〉0.05）.LEF组患者术后1、3、5年的血清肌酐水平和24 h尿蛋白定量分别为（101±14）、（112±21）、（132±26）μmol/L和（896±98）、（1 232±126）、（1 458±110）mg;MMF组分别为（98±16）、（108±23）、（127±21）μmol/L和（912±101）、（1 275±117）mg、（1 483±133）mg（均为P〉0.05）.LEF组患者中,41%（13/32）出现不同程度的排斥反应,给予抗排斥反应治疗后,逆转5例（38%,5/13）,移植肾失功8例;MMF组患者中,34%（11/32）出现不同程度的排斥反应,给予抗排斥反应治疗后,逆转5例（45%,5/11）,移植肾失功6例.LEF组和MMF组患者术后感染发生率分别为13%（4/32）和19%（6/32）（P〉0.05）.两组药物不良反应发生率亦无统计学意义（均为P〉0.05）.结论 肾移植患者术后长期应用LEF进行免疫抑制治疗是安全、有效的.     

肾移植术后早期严重肺部感染患者外周血CD4+T淋巴细胞计数的临床意义

Objective To explore the clinical implication of peripheral blood CD4+ T-cell counts in renal allograft recipients with severe pulmonary infection in the early stage after kidney transplantation. Methods From February 2007 to June 2008, we investigated the variation of peripheral blood CD4+ T-cell counts using flow cytometry in 28 cases of severe pulmonary infection 1 ～6 months after kidney transplantation (infection group), and 30 cases (control group) randomly selected that had stable situation and normal kidney function in the same period. Results CD4+ T-cell counts on the day of admission in infection group were significantly lower than in control group (184.1 ±117.5/μl vs. 518.6±232.7/μl, P<0.01 ). In infection group, 5 patients died and 4 of them had obviously declining trends of CD4+ T-cell counts during hospitalization course. Comparing to the day of admission, CD4+ T-cell counts of those survivors in infection group were significantly increased (184.1±117.5/μl vs. 406.5±163.9/μl, P<0.01) when infections were controlled. ROC analysis showed that CD4+ T-cell counts on the day of admission were accurate enough to identify who were susceptible to infection. In detail, the area under the curve (AUC) was 94.9% (P<0.01). CD4+ T-cell counts of 220/μl displayed the minimal misdiagnosis rate. Conclusions The variations of CD4+ T-cell counts are correlated to onset and progression of severe pulmonary infection in the early stage after kidney transplantation. Those who had CD4+ T-cell counts lower than 220/μl were at high risk of pulmonary infection. Direct measure and dynamic analysis of CD4+ T-cell subset have an important role in optimizing treatment and predicting prognosis of severe pulmonary infection in the early stage after kidney transplantation.     

西罗莫司在肾移植术后远期各类并发症患者中的转换应用

目的 探讨以钙调磷酸酶抑制剂(CNI)为主要免疫抑制方案的肾移植受者术后远期发生各类并发症时,应用两罗莫司(SRL)转换治疗方案的有效性及安全性.方法 肾移植术后远期38例采用CNI的患者因发生各类并发症而转换为SRL治疗,其中慢性移植肾肾病(CAN)17例、肿瘤10例、糖尿病3例、移植肾动脉狭窄(TRAS)球囊扩张术后2例、CNI毒性肝损害2例、丙型肝炎病毒(HCV)感染2例、面容改变1例及马兜铃酸肾病1例.SRL首剂负荷剂量为4～6 mg,维持剂量为1～2 mg/d,血SRL浓度维持在4～8 μg/L.使用SRL当天,CNI的用量减少一半,并在达到血SRL目标浓度的2～4周内逐渐撤除.转换后对患者随访了3～46个月,动态观察血常规、血肌酐、血糖、血脂及尿蛋白等指标,观察不良反应及监测急性排斥反应、移植肾功能丧失和肺部感染等并发症的发生.结果 转换治疗后.17例CAN患者中12例肾功能明显好转,血肌酐水平由转换前的(195.8±40.0)μmol/L降至(159.1±37.5)μmol/L(P<0.05);10例肿瘤患者中7例存活良好,2例发生肿瘤远处转移,1例死亡,血肌酐水平由转换前的(102.8±28.0)μmol/L降至转换后3个月的(77.8±25.6)μmol/L(P<0.05);2例TRAS球囊扩张术后患者肾功能恢复正常,TRAS未再发生;3例糖尿病患者血糖水平有所改善;2例CNI肝毒性者转换后肝功能恢复正常;2例HCV感染者肝功能稳定,病毒RNA拷贝水平下降;1例面容改变者症状明显好转;1例马兜铃酸肾病者未发生肿瘤.转换治疗后,所有患者均未发生急性排斥反应,不良反应主要为高脂血症3例、蛋白尿3例及白细胞减少1例.结论 肾移植术后采用CNI者发生CAN等远期并发症时,将CNI转换为西罗莫司治疗是安全,有效的.     

肾移植术后早期严重肺部感染患者外周血CD4+T淋巴细胞计数的临床意义

目的 探讨肾移植术后早期严重肺部感染患者外周血CD4+T淋巴细胞计数的临床意义.方法 采用流式细胞术检测2007年2月至2008年6月期间,肾移植术后早期发生严重肺部感染的28例患者(感染组)外周血CD4+T淋巴细胞计数的变化,并随机选取同期肾移植术后病情稳定的30例患者(对照组)作为对照.结果 肾移植术后早期,感染组患者入院第1天CD4+T淋巴细胞计数显著低于对照组,分别为(184.1±117.5)个/μl和(518.6±232.7)个/μl(P<0.01).感染组患者中有5例治疗无效死亡,其中4例CD4+T淋巴细胞计数呈持续降低趋势;感染组中存活的患者在治疗恢复后,CD4+T淋巴细胞计数明显上升至(406.5±163.9)个/μl,与治疗前比较,P<0.01.受试者工作特征(ROC)曲线分析表明,CD4+T淋巴细胞计数减少能作为判断发生肺部感染的有效指标,其曲线下面积(AUC)为94.9%(P<0.01),CD4+T淋巴细胞计数为220个/μL时,其特异度为100%.结论 外周血CD4+T淋巴细胞的变化与肾移植术后早期严重肺部感染的转归密切相关.CD4+T淋巴细胞计数低于220个/μl的患者发生感染的可能性极大;测定外周血CD4+T淋巴细胞计数并动态分析对于优化治疗和判断预后有重要的参考价值.     

肾移植后因免疫抑制剂的不良反应转换应用咪唑立宾的效果

Objective To investigate the efficacy and safety of conversion therapy to mizoribine (MZR) for renal transplant patients who suffered MMF or Aza adverse reaction. Methods In 56 patients with adverse reactions at different time points after renal transplantation, there were 23 cases of pulmonary infection, 14 cases of bone marrow depression, 6 cases of hepatic functional lesion and 13 cases of diarrhea. The immunosuppressive protocols of these patients were changed to CNI + MZR + Pre when the adverse reaction occurred. During the follow-up period (11 to 53 months), the effect and adverse events of conversion treatment were observed. Results After conversion treatment, 1 of 23 patients with pulmonary infection was re-infected after 26 months and finally died of heart and lung function failure. In 14 patients with bone marrow depression, blood test returned to normal in 13cases. Six patients with hepatic functional lesion were administered hepatoprotection treatment and their liver function was restored without recurrence of impaired liver function. All 13 patients with diarrhea were relieved without recurrence. The serum creatinine was 123 ± 21.3 μmol/L and 119±18. 2 μmol/L before and after the conversion therapy respectively (P＞0. 05). During the follow-up period, all patients' graft function was good. The incidence of rejection was 1.7 % (1 case). Nine patients (16. 1 %) had a higher level of uric acid after conversion. One patient had finger and toe joint pain. The symptoms were relieved after symptomatic treatment. Conclusion There were high security and good effect of conversion therapy to MZR due to MMF or Aza adverse reaction. Besides, MZR conversion therapy for renal transplantation patients provided a new option for individual immunosuppression.     

肾移植后应用辛伐他汀致横纹肌溶解症一例

本院有1例肾移植受者术后应用辛伐他汀致横纹肌溶解症的病例,现报告如下. 患者为男性,47岁.既往无肝炎病史,有高脂血症病史2年,长期口服血脂康胶囊.     

五酯胶囊对肾移植受者他克莫司血药浓度的影响

目的：探讨应用五酯胶囊提高肾移植受者他克莫司血药浓度的可能性。方法：将50例肾移植术后长期服用他克莫司的受者（〉6个月）作为研究对象,他克莫司和五酯胶囊同时服用的受者为五酯胶囊组（26例）,单纯口服他克莫司的受者为对照组（24例）,检测两组他克莫司血药浓度谷值及肝、肾功能和空腹血糖,作为临床评价指标。结果：五酯胶囊组服药1周后他克莫司血药浓度谷值比服药前增加了（3.051±0.774）ng/mL,增幅达56.91%,服药前后比较差异有显著性（P〈0.01）;与对照组服药后比较亦有显著性差异（P〈0.01）。停用五酯胶囊1周后,他克莫司血药浓度谷值明显降低,降幅达35.36%,停药前后差异有显著性（P〈0.01）。他克莫司和五酯胶囊联用对肝、肾功能指标无明显不良影响,对4例肝功能异常的受者有降低丙氨酸氨基转移酶、天冬氨酸氨基转移酶的作用,未发现与药物相关不良反应导致停止治疗的记录。结论：五酯胶囊能明显提高他克莫司血药浓度谷值,同时可能对肝功能有保护作用。     

肾移植术后早期严重肺部感染患者外周血CD4+T淋巴细胞计数的临床意义

Objective To explore the clinical implication of peripheral blood CD4+ T-cell counts in renal allograft recipients with severe pulmonary infection in the early stage after kidney transplantation. Methods From February 2007 to June 2008, we investigated the variation of peripheral blood CD4+ T-cell counts using flow cytometry in 28 cases of severe pulmonary infection 1 ～6 months after kidney transplantation (infection group), and 30 cases (control group) randomly selected that had stable situation and normal kidney function in the same period. Results CD4+ T-cell counts on the day of admission in infection group were significantly lower than in control group (184.1 ±117.5/μl vs. 518.6±232.7/μl, P<0.01 ). In infection group, 5 patients died and 4 of them had obviously declining trends of CD4+ T-cell counts during hospitalization course. Comparing to the day of admission, CD4+ T-cell counts of those survivors in infection group were significantly increased (184.1±117.5/μl vs. 406.5±163.9/μl, P<0.01) when infections were controlled. ROC analysis showed that CD4+ T-cell counts on the day of admission were accurate enough to identify who were susceptible to infection. In detail, the area under the curve (AUC) was 94.9% (P<0.01). CD4+ T-cell counts of 220/μl displayed the minimal misdiagnosis rate. Conclusions The variations of CD4+ T-cell counts are correlated to onset and progression of severe pulmonary infection in the early stage after kidney transplantation. Those who had CD4+ T-cell counts lower than 220/μl were at high risk of pulmonary infection. Direct measure and dynamic analysis of CD4+ T-cell subset have an important role in optimizing treatment and predicting prognosis of severe pulmonary infection in the early stage after kidney transplantation.     

肾移植供肾MDR1基因多态性对FK506肾毒性和血药浓度的影响

目的：观察肾移植术后供肾多药耐药基因（MDR1）外显子26及外显子21的基因型对他克莫司（FK506）急慢性肾毒性和血药浓度的影响。方法回顾51例肾移植术后常规使用FK506＋MMF＋Pred三联免疫抑制用药方案的患者资料。通过基因组测序检测肾移植供者MDR1 exon26和exon21的基因型,比较不同供肾基因型的患者FK506的用量、血药浓度及和肾毒性的差异。结果在术后1年时比较内生肌酐清除率时,在exon26中,TT型的内生肌酐清楚率明显低于CC型和CT型（P＜0.05）,在exon21中,低表达型（TT型）明显低于高表达型（GG/GT/GA/AT型）（P＜0.05）;在比较术后1个月内的移植肾急性肾中毒发生率时,exon21中低表达型明显高于高表达型（P＜0.05）。结论在保护移植肾功能,减少FK506的急慢性肾毒性上,exon26的CC/CT型和exon21的高表达型明显优于exon26的的TT型和低表达型。     

尿液中IP-10、Mig和OPG含量与移植肾排斥反应相关性的临床研究

目的 探讨肾移植受者的尿液中人干扰素诱导蛋白10(IP-10)、γ干扰素诱导单核细胞因子(Mig)和破骨细胞抑制因子(OPG)含量与移植肾排斥反应的相关性.方法 采用回顾性巢式病例对照研究,以活检证实发生急性排斥反应的受者20例为排斥组,另选肾移植后肾功能恢复良好的受者20例为对照组,于术后第1天起,连续30d留取晨尿,利用Luminex 2000检验操作平台,通过PlexMark三联肾损伤标志物试剂盒检测两组受者移植后30d内每天的尿液中IP-10、Mig和OPG的水平.结果 排斥组的尿IP-10为(394.7±67.3) ng/L,明显高于对照组的(10.9±3.8) ng/L(P＜0.05).排斥组的尿Mig水平为(443.0±88.9) ng/L,对照组仅为(15.7±6.99) ng/L,排斥组明显高于对照组(P＜0.05).而尿OPG的峰值水平,两组间的差异无统计学意义.排斥组在排斥时间段尿IP-10和Mig的水平显著高于非排斥时间段,差异有统计学意义(P＜0.01),其水平在不同时刻均与血肌酐浓度呈现明显的相关性,IP-10与血肌酐的相关系数(R2)=0.8673,P＜0.01,Mig与血肌酐的R2=0.7951,P＜0.01,IP-10和Mig的变化时间早于血肌酐,而排斥前后OPG的差异无统计学意义.结论 尿液中IP-10和Mig含量的升高与移植肾急性排斥反应相关,可早期反映亚临床肾小管损伤,且其变化早于血肌酐的升高,有望成为独立指标来预测急性排斥反应的发生.