肾移植后不同免疫抑制方案的效果及不良反应的临床分析

Objective To summarize the incidence and treatment experience of the effectiveness and adverse reactions of the different immunosuppressive protocols and to increase the long-term survival rate in kidney recipients. Methods Single-center retrospective analysis was performed on 3102 cases of kidney transplant recipients in effectiveness and adverse reactions of different immunosuppressive protocols. The immunosuppressive protocols were as follows: CsA + Aza + Pred,low dose CsA + MMF + Pred, low dose Tac + MMF + Pred, low dose CsA + SRL + Pred, and low dose Tac+ SRL+ Pred. Results The 1-, 5-, 10-year survival rate of patients/kidney in low dose CsA + MMF + Pred protocol was higher than that in CsA + Aza + Pred protocol. The incidence of adverse reactions, such as hypertension, hyperuricemia, kidney and liver toxicity, and leukopenia was significantly lower, but the incidence of diarrhea was significantly higher in CsA + MMF + Pred protocol than in CsA + Aza + Pred protocol (all P＜0. 01). The incidence of hyperglycemia was significantly higher (P＜0. 05), and that of hairy and gingival hyperplsia was significantly lower (P＜0. 05) in low dose Tac+ MMF+ Pred than in low dose CsA+ MMF+ Pred protocol. The incidence of hyperlipidemia in low dose CsA (or Tac)+ SRL + Pred was significantly higher than in CsA (or Tac)+ MMF+ Pred protocol (P＜0. 05). The incidence of hirsutism in low dose Tac + SRL + Pred was significantly lower than that in CsA + SRL + Pred protocol (P ＜ 0. 05). The incidence of hyperglycemia in low dose Tac + SRL + Pred was significantly higher than that in low dose CsA + SRL + Pred protocol. Conclusion The triple drug protocol with a low dose of CsA (or Tac)+ MMF+ Pred significantly improved the survival of renal transplant recipients and graft, and reduced the incidence of adverse reactions, especially Tae + MMF + Pred protocol. Adjustment of the immunosuppressant dosage and protocol, improvement of eating habits, exercise, reduction of blood pressure, reduction of blood lipid, and control of blood glucose were particularly important in preventing and controlling adverse reactions during kidney transplantation.     

肾移植后不同免疫抑制方案的效果及不良反应的临床分析

Objective To summarize the incidence and treatment experience of the effectiveness and adverse reactions of the different immunosuppressive protocols and to increase the long-term survival rate in kidney recipients. Methods Single-center retrospective analysis was performed on 3102 cases of kidney transplant recipients in effectiveness and adverse reactions of different immunosuppressive protocols. The immunosuppressive protocols were as follows: CsA + Aza + Pred,low dose CsA + MMF + Pred, low dose Tac + MMF + Pred, low dose CsA + SRL + Pred, and low dose Tac+ SRL+ Pred. Results The 1-, 5-, 10-year survival rate of patients/kidney in low dose CsA + MMF + Pred protocol was higher than that in CsA + Aza + Pred protocol. The incidence of adverse reactions, such as hypertension, hyperuricemia, kidney and liver toxicity, and leukopenia was significantly lower, but the incidence of diarrhea was significantly higher in CsA + MMF + Pred protocol than in CsA + Aza + Pred protocol (all P＜0. 01). The incidence of hyperglycemia was significantly higher (P＜0. 05), and that of hairy and gingival hyperplsia was significantly lower (P＜0. 05) in low dose Tac+ MMF+ Pred than in low dose CsA+ MMF+ Pred protocol. The incidence of hyperlipidemia in low dose CsA (or Tac)+ SRL + Pred was significantly higher than in CsA (or Tac)+ MMF+ Pred protocol (P＜0. 05). The incidence of hirsutism in low dose Tac + SRL + Pred was significantly lower than that in CsA + SRL + Pred protocol (P ＜ 0. 05). The incidence of hyperglycemia in low dose Tac + SRL + Pred was significantly higher than that in low dose CsA + SRL + Pred protocol. Conclusion The triple drug protocol with a low dose of CsA (or Tac)+ MMF+ Pred significantly improved the survival of renal transplant recipients and graft, and reduced the incidence of adverse reactions, especially Tae + MMF + Pred protocol. Adjustment of the immunosuppressant dosage and protocol, improvement of eating habits, exercise, reduction of blood pressure, reduction of blood lipid, and control of blood glucose were particularly important in preventing and controlling adverse reactions during kidney transplantation.     

肾移植后不同免疫抑制方案的效果及不良反应的临床分析

Objective To summarize the incidence and treatment experience of the effectiveness and adverse reactions of the different immunosuppressive protocols and to increase the long-term survival rate in kidney recipients. Methods Single-center retrospective analysis was performed on 3102 cases of kidney transplant recipients in effectiveness and adverse reactions of different immunosuppressive protocols. The immunosuppressive protocols were as follows: CsA + Aza + Pred,low dose CsA + MMF + Pred, low dose Tac + MMF + Pred, low dose CsA + SRL + Pred, and low dose Tac+ SRL+ Pred. Results The 1-, 5-, 10-year survival rate of patients/kidney in low dose CsA + MMF + Pred protocol was higher than that in CsA + Aza + Pred protocol. The incidence of adverse reactions, such as hypertension, hyperuricemia, kidney and liver toxicity, and leukopenia was significantly lower, but the incidence of diarrhea was significantly higher in CsA + MMF + Pred protocol than in CsA + Aza + Pred protocol (all P＜0. 01). The incidence of hyperglycemia was significantly higher (P＜0. 05), and that of hairy and gingival hyperplsia was significantly lower (P＜0. 05) in low dose Tac+ MMF+ Pred than in low dose CsA+ MMF+ Pred protocol. The incidence of hyperlipidemia in low dose CsA (or Tac)+ SRL + Pred was significantly higher than in CsA (or Tac)+ MMF+ Pred protocol (P＜0. 05). The incidence of hirsutism in low dose Tac + SRL + Pred was significantly lower than that in CsA + SRL + Pred protocol (P ＜ 0. 05). The incidence of hyperglycemia in low dose Tac + SRL + Pred was significantly higher than that in low dose CsA + SRL + Pred protocol. Conclusion The triple drug protocol with a low dose of CsA (or Tac)+ MMF+ Pred significantly improved the survival of renal transplant recipients and graft, and reduced the incidence of adverse reactions, especially Tae + MMF + Pred protocol. Adjustment of the immunosuppressant dosage and protocol, improvement of eating habits, exercise, reduction of blood pressure, reduction of blood lipid, and control of blood glucose were particularly important in preventing and controlling adverse reactions during kidney transplantation.     

环孢素A转换为他克莫司对慢性移植肾肾病患者的治疗效果

目的 探讨由环孢素A(CsA)转换为他克莫司(Tac)为主的免疫抑制方案对慢性移植肾肾病(CAN)患者的治疗效果.方法 选择接受同种肾移植后发生CAN的患者153例,患者肾移植后均采用CsA、吗替麦考酚酯(MMF)及泼尼松(Pred)的免疫抑制方案.根据是否以Tac替换CsA将患者分为两组.(1)CsA组:45例,进入研究后患者维持原免疫抑制方案.(2)Tac组:108例,进入研究后将CsA转换为Tac,停用CsA后立即开始服用Tac,MMF和Pred的用法同CsA组.对所有患者随访12个月,观察人/移植肾存活率、急性排斥反应发生率、移植肾功能、24 h尿蛋白定量、移植肾穿刺病理学活检及免疫抑制剂的不良反应等指标.结果 随访12个月时,CsA组和Tac组患者存活率均为100%,移植肾存活率分别为86.6%和93.5%(P＜0.05);急性排斥反应发生率分别为4.4%(2/45)和3.7%(4/108)(P＞0.05),6例发生急性排斥反应的患者均经甲泼尼龙冲击治疗3 d后逆转.Tac组患者移植肾功能明显改善,并且出现重度蛋白尿、重度肾间质纤维化和肾小管萎缩的患者比例较CsA组显著减少(P＜0.05).Tac组有13.8%(15例)的患者出现轻度血糖增高,发生率显著高于CsA组的4.4%(2例)(P＜0.05);Tac组有22.2%(24例)的患者发生高血压,发生率显著低于CsA组的55.6%(25例)(P＜0.05);17例因使用CsA而出现牙龈增生和多毛症者,经转换治疗后,症状均明显好转.结论 由CsA转换为Tac为主的免疫抑制方案能够显著改善CAN患者的移植肾功能,延缓CAN的发展,转换过程中未发生严重Tac不良反应并且改善了使用CsA时出现的不良反应.

Abstract：

Objective To investigate the effect of conversion from cyclosporine A (CsA) to tacrolimus (Tac) on chronic allograft nephropathy (CAN). Methods 153 CAN patients undergoing kidney transplantation received CsA, mycophenolate mofetil (MMF) and prednisone (CsA-MMF-Pred) regimen after kidney transplantation, and divided into 2 groups according to whether CsA were maintained in the immunosuppressive regimen: CsA + MMF + Pred group (CsA group, n = 45); Tac + MMF + Pred group (Tac group, n = 108). The patients were followed up with patient/kidney survival rate, acute rejection incidence, renal function, 24-h proteinuria and adverse events of immunosuppressive drugs for 12 months. Results Compared with CsA group, the transplanted kidney survival rate was significantly higher in Tac group (93. 5 % vs 86.6 %, P＜0. 05). Acute rejection (AR) was diagnosed in 4. 4 % (2/45) of recipients in CsA group and 3. 7 % (4/108) in Tac group (P＞0. 05) respectively. Acute rejection (2 cases in CsA group and 4 in Tac group) was reversed by 500 mg of methylprednisolone for consecutive 3 days, and the patients in Tac group showed a significantly lower degree of interstitial fibrosis and tubular atrophy (IF/TA) (P＜0. 05).Renal allograft functions and 24-h proteinuria during a follow-up period of 12 months were significantly improved in Tac group (P ＜ 0. 05). Incidence of mild hyperglycemia in Tac Group (13.8 %, 15/108) was significantly higher than in CsA group (4.4 %, 2/45), and that of hypertension in Tac group (22. 2 %, 24/108) was significantly lower than in CsA group (55.6 %,25/45). CsA-related side effects (such as hirsutism and gingival hypertrophy) in 17 patients were greatly improved after conversion from CsA to Tac treatment. Conclusion The conversion from CsA to Tac on the patients with CAN can improve renal allograft function, retard the progression of renal allograft dysfunction, reduce the incidence of CsA-related side effects and not generate serious adverse effects of Tac.     

不同剂量咪唑立宾在临床肾移植中的应用研究

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 MZR Ⅰ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%(86/100),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(P<0.05),而MZRⅡ组与其他两组的差异均无统计学意义(P>0.05).MZR Ⅰ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致顽同性腹泻者,可将含咪唑立宾的免疫抑制方案作为首选.

Abstract：

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. Results 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 hyperuricacidemia 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.     

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

目的 探讨肾移植术后因不良反应而将吗替麦考酚酯(MMF)或硫唑嘌呤(Aza)转换为咪唑立宾(MZR)的有效性和安全性.方法 56例肾移植受者术后发生肺部感染23例,骨髓抑制14例,肝功能损害6例,腹泻13例.所有患者均采用以钙调磷酸酶抑制剂(CNI)+MMF(或Aza)+泼尼松(Pred)的免疫抑制方案,出现不良反应时,转换应用了CNI+MZR+Pred.转换治疗后随访(33.2±17.4)个月(11～53个月),观察转换治疗后的效果和不良反应.结果 转换治疗后,23例肺部感染的患者,1例再次出现肺部感染,死于心、肺功能衰竭,其余均未再出现肺部感染;骨髓抑制的14例患者中,13例血常规恢复正常,1例未恢复;肝功能损害的6例患者经转换治疗后,肝功能均恢复正常;13例腹泻患者的症状均缓解.转换前,患者血清肌酐为(123±21.3)μmol/L,转换后,血清肌酐为(119±18.2)μmol/L,二者比较,差异无统计学意义(P＞0.05).转换治疗后,有1例(1.7%)患者发生排斥反应,9例(16.1%)出现不同程度的血尿酸升高,1例出现指(趾)关节疼痛等症状,均经对症治疗后好转.结论 在肾移植术后发生免疫抑制剂不良反应时,转换应用咪唑立宾效果良好,安全性高,为肾移植后患者的个体化免疫抑制方案的应用提供一种新的选择.

Abstract：

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.     

两种免疫抑制方案在肾移植中应用的不良反应对比分析

目的 评价免疫抑制剂的不同组合在肾移植中应用的安全性。方法 回顾分析肾移植患者的临床资料，术后采用环孢素A(CsA)、硫唑嘌呤(Aza)及泼尼松(Pred)三联用药预防排斥反应者37例(Aza组)，采用CsA、霉酚酸酯(MMF)及Pred三联用药者35例(MMF组)。比较分析两个组用药后的药物不良反应。结果 在消化道反应、白细胞减少、全血细胞减少以及继发感染发生率等方面，MMF组与Aza组的差异无显著性(P＞0．05)，而肝功能损伤的发生率，Aza组明显高于MMF组(P＜0．05)。结论 在药物性肝损伤方面，以MMF、CsA及Pred组成的免疫抑制方案较CsA、Aza及Pred方案相对安全。     

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.     

肾移植长期受者贫血的特征及相关因素分析

目的 分析肾移植长期受者贫血的特征及其影响因素。 方法 以肾移植长期受者258例为研究对象,总结贫血的性质和发生率,分析贫血与红细胞生成素（EPO）、肾小管功能、肾功能、排斥反应、免疫抑制药物及心脑血管并发症的关系。 结果 258例均为首次肾移植受者,贫血的总发生率为41.1％。受者大部分为正细胞正色素性贫血,少部分为小细胞低色素性贫血,极少部分为溶血性贫血。贫血受者中,大部分为EPO缺乏,少部分为EPO抵抗。受者的血红蛋白（Hb）与估算肾小球滤过率（eGFR）、肌酐清除率（Ccr）呈正相关（r = 0.348, P ＜ 0.01;r = 0.351,P ＜ 0.01）;与N-乙酰氨基葡萄糖苷酶（NAG）呈负相关（r = -0.327,P ＜ 0.01）。在Scr正常的情况下,贫血组肾小管病变比非贫血组严重。贫血受者急、慢性排斥反应的发生率显著高于非贫血受者（P ＜ 0.01)。环孢素+硫唑嘌呤+泼尼松方案（CsA+Aza+Pred ）贫血的发生率为69.0％;环孢素+霉酚酸酯+泼尼松方案（CsA+MMF+Pred）贫血的发生率为35.8％;他可莫司+霉酚酸酯+泼尼松方案（FK506+MMF+Pred)贫血的发生率为34.8％;西罗莫司（雷帕霉素）+霉酚酸酯+泼尼松方案 （SRL+MMF+Pred）贫血的发生率为41.7％。骨髓抑制是硫唑嘌呤最常见的不良反应。Hb与硫唑嘌呤的使用时间呈负相关（r = -0.354,P ＜ 0.01);Hb与霉酚酸酯的剂量（2~3 g/d）及使用时间呈负相关（r = -0.285,P ＜ 0.05;r = -0.372,P ＜ 0.01）;Hb与雷帕霉素的剂量（2~5 mg/d）及使用时间呈负相关（r = -0.278,P ＜ 0.05; r = -0.359,P ＜ 0.01）。贫血受者心脑血管病变发生率显著高于非贫血受者（P ＜ 0.01）。 结论 肾移植长期受者贫血的发生率相当高。贫血不仅与肾功能、肾小管间质病变相关,而且也与EPO、排斥反应、免疫抑制药物相关。贫血是肾移植受者出现心脑血管并发症的高危因素。     

西罗莫司在肝移植术后肾功能异常患者中的应用

目的 探讨西罗莫司替换钙调磷酸酶抑制剂治疗肝移植术后肾功能不全的安全性和有效性.方法 北将肝移植术后发生肾功能不全的62例患者随机分为对照组和转换组.对照组29例,继续采用Tac(或CsA)、MMF及Pred的方案,血Tac(或CsA)浓度调整在治疗窗范围的下限;转换组33例,用SRL替换原方案中的Tac(或CsA),SRL的起始用量为2 mg/d,以后根据血SRL浓度及不良反应作相应调整,Tac(或CsA)减少至原用量的1/3～1/2,3 d后停用,MMF和Pred的用法不变.转换治疗后,对患者的肝肾功能、急性排斥反应及存活率进行随访监测,并观察患者在转换治疗期间发生的不良反应.结果 共有49例患者痊愈或者好转,13例死亡,对照组死亡8例,转换组死亡5例.随访9～51个月,转换组存活患者肝功能稳定,均未发生急性排斥反应.两组存活患者肾功能恢复后均未再出现反复,且转换组患者肾功能恢复时间明显缩短,治疗效果较好.转换组存活患者未发生严重不良反应,与对照组肺部感染发生率的比较,差异无统计学意义(P>0.05).结论 肝移植术后并发肾功能不全时,采用西罗莫司替换原免疫抑制方案中的CNI治疗是安全有效的.     

儿童肾移植的临床研究

目的 总结儿童肾移植的临床经验.方法 回顾性分析1980年6月至2008年12月41例儿童肾移植的临床资料,其中1980-1993年(G1)有8例患儿,均未进行免疫诱导,术后采用以环孢素A+硫唑嘌呤+泼尼松为基础的免疫抑制方案;1994-2001年(G2)有18例患儿,均应用抗淋巴细胞球蛋白免疫诱导,术后采用他克莫司(或环孢素A)+吗替麦考酚酯(或硫唑嘌呤)+泼尼松的方案;2002年后(G3)有15例患儿,均应用抗白细胞介素-2受体单克隆抗体(IL-2RA)免疫诱导,术后采用他克莫司(或环孢素A)+吗替麦考酚酯+小剂量泼尼松(或无泼尼松)的方案.分别对三个阶段患儿术后急性排斥反应(AR)和移植肾功能恢复延迟(DGF)等并发症发生率、存活率及生长发育情况等进行比较.结果 41例患儿术后1、3、5年人/肾存活率分别为97.6%/90.2%、95.1%/82.9%和90.2%/75.6%,其中G1为87.5%/75.0%、75.0%/50.0 %和75.0%/50.0%、G2为100.0%/94.4 %、100.0%/83.3%和94.4%/72.2%以及G3为100.0%/100.0%、100.0%/100.0%和100.0%/93.3%,G3明显高于G1(P<0.05),但与G2无明显差异.41例中共有13例发生AR,发生率为31.7%,其中G3的AR发生率分别为13.3%,明显低于G1和G2的50.0%和38.9%(P<0.01).G1、G2和G3患儿的身高分别增长了(2.9±0.6)、(3.2±0.6)和(3.8±0.9)cm,G3患儿身高的增长幅度最为明显(P<0.05).G1、G2和G3患儿间DGF发生率无明显差异,高血压和感染是最为多见的并发症.结论 良好的组织配型、适宜的手术方法、恰当的免疫抑制剂血药浓度及AR早期诊断是保证儿童肾移植成功的关键.IL-2RA免疫诱导能够有效地降低AR发生率,而小剂量激素或无激素方案最大程度的改善了影响患儿骨骼发育的限制因素,促进患儿生长.     

The influence of HLA mismatches and immunosuppression on kidney graft survival: an analysis of more than 1300 patients

New immunosuppressive drugs used in kidney transplantation decreased the incidence of acute rejection. It was hypothesized that, with their power, the importance of HLA matching was decreased. To evaluate the influence of HLA matching, immunosuppression, and other possible risk factors, we analyzed data of 1314 consecutive deceased donor kidney transplantation. We divided the patient population into 4 cohorts, according to the era of transplantation: era 1, before 1990, azathioprine (Aza) and cyclosporine (Csa) no microemulsion; era 2, between 1990 and 1995, Csa microemulsion; era 3, between 1996 and 2000, wide use of mycophenolate mofetil (MMF) and anti-thymocyte globulin (ATG); and era 4, after 2000, marked by sirolimus and tacrolimus (TAC) use. Multivariate analysis compared death-censored graft survival. Using as reference the results obtained with 0 HLA mismatches, we verified, during era 1 and era 2, an increased risk of graft loss for all of the subgroups with HLA mismatch >0. However, during era 3 and era 4, the number of HLA mismatches did not influence graft survival. Although acute rejection and delayed graft function, which decreased in the later periods, remained as prognostic factors for graft loss. Considering the immunosuppressive protocol with Csa+Aza+Pred as reference, protocols used after 1995 with Pred+Csa+ATG, with Pred+Csa+MMF, and with Pred+Tac+MMF presented better survival results. Results showed that the significance of HLA matching decreased while the results improved with the new immunosuppressant drugs. These observations support the hypothesis that the weakened importance of HLA matching may be a consequence of the increasing efficacy of the immunosuppression.     

Long-term renal allograft function on a tacrolimus-based, pred-free maintenance immunosuppression comparing sirolimus vs. MMF.

It is not known how different steroid-free immunosuppressive combinations affect renal graft survival and long-term kidney transplant function. Here we sought to compare the impact on graft survival and long-term graft function of two tacrolimus (Tac)-based, prednisone-free maintenance immunosuppressive protocols: Tac/Mycophenolate Mofetil (MMF) vs. Tac/Sirolimus (SRL). Renal transplant patients given induction therapy with IL2-RA and methylprednisolone on days 0, 1 and 2 post-transplant were prospectively randomized to two maintenance immunosuppressive regimens with Tac/MMF (n = 45) or Tac/SRL (n = 37). During the 3-year follow-up the following data were collected: patient survival, renal allograft survival, incidence of acute rejection and glomerular filtration rate (GFR) at different time-points post-transplant. Cumulative graft survival was significantly different in the two groups: one kidney loss in the Tac/MMF vs. six kidney losses in the Tac/SRL (log-rank test p = 0.04). GFR at different time-points post-transplant was consistently and statistically better in the Tac/MMF than in the Tac/SRL group. The slope of GFR decline per month was flatter in the Tac/MMF than in the Tac/SRL group. This study showed that renal graft survival and graft function were significantly lower in the combination of Tac/SRL than Tac/MMF.     

西罗莫司在肾移植后近期应用中的疗效分析

目的探讨西罗莫司在肾移植后近期治疗中的应用效果。方法收集使用不同免疫抑制剂方案治疗的50例肾移植患者资料,应用环孢素A(CsA)+西罗莫司(SRL)+泼尼松(Pred)的18例患者为实验组,应用CsA+吗替麦考酚酯(MMF)+Pred的32例患者为对照组。对移植后6个月内的急性排斥反应、移植肾功能及血脂情况进行观察。结果实验组发生排斥反应2例,排斥反应发生率为11.1%;对照组为7例,发生率为21.8%,差异有统计学意义(P<0.05)。术后1个月实验组和对照组肾功能比较差异有统计学意义(P<0.05),术后1周及术后3、6个月2组间比较差异无统计学意义(P>0.05)。术后1、3、6个月实验组患者总胆固醇、甘油三酯及低密度脂蛋白水平均高于对照组,差异有统计学意义(P<0.05),术后1周2组间比较差异无统计学意义(P>0.05)。结论肾移植后近期采用CsA、SRL和Pred联合的免疫抑制治疗方案,可取得较好的免疫抑制效果。显著减少移植肾的急性排斥反应发生率,但高脂血症是SRL临床常见的不良反应。     

雷公藤多苷对移植肾长期存活率的影响

目的:探讨雷公藤多苷(TW)作为免疫抑制剂对肾移植患者长期存活率的疗效及副作用.方法:104例患者在肾移植术后采用TW 泼尼松(Pred) 环孢霉素(GsA) 硫唑嘌呤(AZa)免疫抑制剂治疗,48例患者在肾移植术后采用Pred GsA 骁悉(MMF)免疫抑制剂治疗,就以下方面对两组患者进行观察比较:(1)术后5年内发生排斥反应及临界改变情况;(2)外周血白细胞下降、肝功能异常的发生率;(3)严重感染情况;(4)出现尿蛋白情况;(5)术后5年内肾功能变化情况及移植肾5年存活率.结果:5年内AZa TW组急性排斥反应及临界改变的发生率较MMF组低,分别为11.5%、16.7%和4.8%、6.3%(P＞0.05);GPT高于正常的发生率分别为7.7%、16.6%(P＞0.05);外周血白细胞低于正常的发生率分别为0.96%、18.8%(P＜0.01);严重感染的发生率分别为1.9%、18.8%(P＜0.05),5年内出现蛋白尿的患者例数分别为17.3%、29.2%(P＞0.05),两组移植肾5年存活率相似,分别为89.6%、85.4%(P＞0.05).结论:在肾移植术后应用CsA Pred AZa TW免疫抑制方案是可行的,既可以使肾移植术后急性排斥反应减少,同时还能减少蛋白尿及慢性排斥反应的发生率下降,为国内提高移植肾长期存活率提供了一条新的途径.     

Increased Risk of Thrombotic Microangiopathy in Patients Receiving a Cyclosporin–Sirolimus Combination

A single-center cohort study of kidney and kidney-pancreas recipients was conducted to evaluate the association between new immunosuppressive regimens and risk of thrombotic microangiopathy (TMA). From January 1st,1996 to December 31, 2002, 368 patients received a kidney or kidney-pancreas transplant at our center. Four immunosuppressive regimens were evaluated as potential risk factors of TMA: cyclosporin + mycophenolate mofetil (CsA + MMF), cyclosporin + sirolimus (CsA + SRL), tacrolimus + myophenolate mofetil (FK + MMF), and tacrolimus + sirolimus (FK + SRL). Thirteen patients developed biopsy-proven TMA in the absence of vascular rejection. The incidence of TMA was significantly different in the four immunosuppressive regimens studied (p < 0.001). The incidence of TMA was highest in the CsA + SRL group (20.7%). The relative risk of TMA was 16.1 [95% confidence interval (CI): 4.3-60.8] for patients in the CsA + SRL group as compared with those in the FK + MMF group. We also investigated in vitro the pathophysiological basis of this association. The CsA-SRL combination was found to be the only regimen that concomitantly displayed pro-necrotic and anti-angiogenic activities on arterial endothelial cells. We propose that this combination concurs to development of TMA through dual activities on endothelial cell death and repair.     

Optimization of the immunosuppressive protocol after lung transplantation.

BACKGROUND: The successful use of tacrolimus (Tac)-based immunosuppressive therapy in organ transplantation and our own positive experience in heart transplantation led us to investigate regimens including this agent at our center for lung transplantation. METHODS: From 1991 to 1998, 86 patients underwent lung transplants at our center and 78 of them were included in this analysis. The first 34 patients were treated with cyclosporin (CsA), azathioprine (Aza), and rabbit antilymphocyte globulin; the subsequent 30 patients received Tac with Aza, and the most recent 12 patients Tac with mycophenolate mofetil (MMF). In addition, all patients received prednisone. RESULTS: The number of acute rejection episodes per 100 patient days was 1.5, 0.6, and 0.3 for three treatment groups, respectively. Similarly, the incidence of refractory acute rejection per 100 patient days was lower in both Tac groups (0.20, 0.03, and 0, respectively). Freedom from acute rejection was highest in the Tac-MMF group (P=0.0037 vs. Tac/Aza, P=0.0007 vs. CsA/Aza). Freedom from recurrent acute rejection was significantly higher in both Tac groups (P=0.027 Tac/ Aza vs. CsA/Aza and P=0.025 Tac/MMF vs. CsA/Aza). The incidence of infections per 100 patient days was similar (0.8, 0.5, and 0.8) in all three treatment groups, with a similar distribution of fungal, bacterial, and viral infections. Freedom from infection also showed no difference. The survival rate was significantly higher for the Tac population, with actuarial 1- and 3-year survival rates of 93% and 71%, compared with the CsA group (71% and 51%, respectively, P=0.04). Prevalence of renal dysfunction (creatinine >2.0 mg/ dL) was 18%, 13%, and 0% in the 3 treatment groups, respectively. The development of glucose metabolism disorders was lower in the CsA group than in the Tac-Aza group (15% vs. 27%, P<0.05). CONCLUSIONS: Tac-based immunosuppressive therapy results in a lower rate of acute rejection after pulmonary transplantation, with similar infection rates and a slightly higher incidence of new onset diabetes mellitus compared with CsA-based therapy.