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

目的 总结肾移植后使用不同免疫抑制方案的效果和不良反应,以提高人/肾的长期存活率.方法 对单中心3102例肾移植受者的临床资料进行回顾性分析,所采用的免疫抑制方案有环孢素A(CsA)+硫唑嘌呤(Aza)+泼尼松(Pred)、低剂量CsA+吗替麦考酚酯(MMF)+Pred、低剂量他克莫司(Tac)+MMF+Pred、低剂量CsA(或Tac)+西罗莫司(SRL)+Pred等方案,分析各方案的效果和不良反应.结果 低剂量CsA+MMF+Pred方案的人/肾1、5、10年存活率均高于CsA+Aza+Pred方案,而高血压、震颤、高尿酸、肝肾毒性、白细胞下降等的发生率显著低于CsA+Aza+Pred方案(P＜0.05),腹泻发生率显著高于CsA+Aza+Pred方案(P＜0.05).低剂量Tac+MMF+Pred方案的高血糖发生率显著高于低剂量CsA+MMF+Pred方案(P＜0.05),多毛症发生率显著低于低剂量CsA+MMF+Pred方案(P＜0.05);低剂量CsA(或Tac)+SRL+Pred方案的腹泻、高尿酸血症、肝肾毒性和多毛症等的发生率显著低于低剂量CsA(或Tac)+MMF+Pred方案(P＜0.05),但高血脂发生率显著高于后者(P＜0.05).以低剂量Tac为基础的方案者高血糖发生率显著应用低剂量CsA者.结论 低剂量CsA(或Tac)+MMF+Pred方案改善了肾移植受者和移植肾的存活,降低了不良反应发生率,尤以低剂量Tac+MMF+Pred方案为优;调整免疫抑制方案或剂量,改善饮食习惯,加强锻炼,优化降血压、降血脂、控制血糖的治疗措施对预防和控制不良反应尤为重要.

Abstract：

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.     

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.     

咪唑立宾在临床肾移植中的应用

目的 观察咪唑立宾(MZR)预防肾移植后排斥反应的效果及不良反应.方法 100例肾移植患者后采用由MZR与环孢素A(CsA)、泼尼松(Pred)组成的三联方案预防排斥反应(MZR组),以100例采用CsA.霉酚酸酯(MMF)与Pred组合者为对照(MMF组),随访12个月,观察急性排斥反应发生率,人、肾存活率以及与药物有关的不良反应.结果 术后12个月内,MZR组及MMF组急性排斥反应发生率分别为11%和9%,差异无统计学意义.MZR组人、肾存活率均为100%,MMF组均为99%.MZR组腹泻、严重肺部感染的发生率分别为4%和1%,明显低于MMF组的12%和6%,而血尿酸升高者(25%)明显多于MMF组(6%),差异均有统计学意义(P<0.05).结论 含咪唑立宾的免疫抑制方案用于预防肾移植后的排斥反应安全、有效,不良反应较少.     

三种小体积肝移植大鼠模型的比较

目的 通过对三种供肝选取方法的比较来探索更简便、稳定的小体积肝移植大鼠模型的建立方法.方法 以Kamada"二袖套"法非动脉化原位大鼠肝移植模型为基础,采取供肝冷灌洗后原位剪除肝叶的方法获取供肝,建立小体积肝移植模型,Ⅰ组以肝中叶作为供肝,Ⅱ组以肝右中叶+右叶作为供肝,Ⅲ组以肝中叶+右叶作为供肝,其中Ⅰ组及Ⅱ组供、受者体重相似,Ⅲ组供者体重比受者轻100～120 g.比较3个组的手术成功率、手术各阶段耗时、术后肝功能以及移植肝组织损伤、排斥反应发生、手术并发症和受者存活情况.结果 Ⅲ组肝叶剪除时间为(8.8±0.7)min,明显短于Ⅱ组的(11.5±1.1)min和Ⅰ组的(10.1±1.0)min(P＜0.01).3个组供肝冷缺血时间、无肝期及受者手术耗时等方面的差异无统计学意义.Ⅲ组肝断面出血和胆漏并发症显著少于Ⅰ组和Ⅱ组;Ⅰ组肝后下腔静脉狭窄及血栓形成明显多于Ⅱ组和Ⅲ组(P＜0.05).3组间术后第1、7天血清丙氨酸转氨酶、胆红素总量和血氨水平的差异无统计学意义.术后第7天,3组间肝损伤及排斥反应分级(Banff分级均为轻度)的差异均无统计学意义.Ⅰ组、Ⅱ组和Ⅲ组的手术成功率分别为80%、85%和85%,3组间的差异无统计学意义.Ⅲ组的7 d存活率为62.5%,高于Ⅰ组的42.9%和Ⅱ组的47.5%,但3组间的差异无统计学意义.Ⅲ组的存活时间为(12.0±2.3)d,长于Ⅰ组的(6.0±0.9)d和Ⅱ组的(7.0±1.3)d,但差异均无统计学意义.结论 采用肝中叶+右叶供肝和供者体重低于受者100～120 g的方案能够简便、快捷的建立稳定的30%小体积肝移植大鼠模型,而且能显著减少肝切除相关并发症.

Abstract：

Objective To explore a simple and effective way of establishing a 30 % small-forsize liver transplantation in rats. Methods SD rats were selected as the donors and recipients. Smallfor-size orthotopic live transplantation was performed using Kamada's two-cuff method. Donor's liver was flushed via abdominal aorta and hepatectomy in situ was done. Animals were divided into 3 groups (40 pairs of rats in each): group Ⅰ , median lobe was used as graft; group Ⅱ, right of median lobe and right lobe were used as graft; group Ⅲ, median and right lobes were used as graft. The body weight of the donor was the same as the recipient in groups Ⅰ and Ⅱ , but 100～ 120 g less than in group Ⅲ. The operating time, 7-day survival and technical complications were compared among these 3 groups. Results The operating time of hepatectomy was shorter in group Ⅲ than in groups Ⅰ and Ⅱ (8. 8±0.7 vs 11.5± 1.1 vs 10.1 ±1.0 min, P＜0.01). The cold ischemia time of graft, the anhepatic time, the operating time of recipient and the transplanting successful rate showed no significant difference among the 3 groups. Compared with groups Ⅰ and Ⅱ , the incidence of bleeding,bile leakage and IVC stricture was significantly decreased in group Ⅲ (P＜0. 05). Other complications after operation showed no significant difference among the 3 groups (P＞0. 05). Group Ⅲ had more 7-days survivors and longer median survival time, but there was no significant difference among the 3groups. Conclusion Small for donor body weight with median and right lobes as graft was a more effective and simple way of establishing a 30 % small-for-size liver transplantation in rats with shorter hepatectomy time and less complications after operation.     

右美托咪啶对七氟醚麻醉患儿麻醉恢复期躁动的影响

Objective To investigate the effect of dexmedetomidine on agitation during recovery from sevoflurane anesthesia in children. Methods Three hundred ASA Ⅰ or Ⅱ children, aged 4-7 yr, weighing 16-30kg, scheduled for elective ear-nose-throat operation under general anesthesia, were randomly divided into 2 groups ( n = 150 each) : control group (group C) and dexmedetomidine group (group D) . Dexmedetomidine 0.5 μg/kg in 20 ml was infused intravenously over 10 min before anesthesia induction in group D, while equal volume of normal Saline was infused in group C. Anesthesia was induced with inhalation of 8 % sevoflurane 5 min after the end of administration . The children were tracheal incubated and mechanically ventilated. Anesthesia was maintained with inhalation of 2 % -3 % sevoflurane. BIS was maintained at 40-60 during operation. The recovery time and agitation within 2 h after operation were recorded. Results There was no significant difference in the recovery time between the two groups ( P > 0.05) . The incidence of agitation was significantly lower in group D than in group C ( P <0.05 ) . Conclusion Dexmedetomidine can reduce the occurrence of agitation during recovery from sevoflurane anesthesia in children.     

曲尼司特对环孢素A诱导的人肾小管上皮细胞向间充质转变的抑制作用

Objective To study the effect of tranilast on cyclosporine A (CsA)-induced epithelial-to-mesenchymal transition in human renal tubular epithelial cells, and investigate the mechanism of its antifibrotic effect. Methods Cultured HK-2 cells were divided into four groups: (1)In the control group, cells were treated without any medicine; (2) The cell were treated with CsA (4. 2μmol/L) for 72 h; (3) The cells were treated with a combination of CsA (4. 2 μmol/L) and tranilast (100μmol/L); (4) The cells were treated with tranilast (100 μmol/L) alone for 72 h.Morphological changes of the cells were assessed by phase-contrast microscopy. The immunofluorescence and Western blotting were adopted to detect the expression of E-cadherin, α-SMA and OPN mRNA and proteins respectively. Results Tranilast could markedly ameliorate the morphological changes of HK-2 cells stimulated by CsA. The irmmunofluorescence staining revealed the expression of E-cadherin was markedly decreased in HK-2 cells stimulated with CsA for 72 as compared with the control group, while the expression of α-SMA and OPN was significantly higher in CsA group than the control group. The expression of E-cadherin in the CsA + Tranilast group was higher than the CsA group, while the expression of α-SMA and OPN in the CsA + Tranilast group was lower than the CsA group. Western blotting showed that protein expression level of E-cadherin in CsA group was dramatically lower than that in the control group (P＜0. 05), while that of α-SMA and OPN in CsA group was significantly higher than in the control group (P＜0.05). The protein expression level of E-cadherin in HK-2 cells in the CsA + Tranilast group was markedly higher than in the CsA group (P＜0.05), and that of α-SMA and OPN in CsA + Tranilast group was significantly lower than in the CsA group (P＜0. 05). Conclusion Tranilast can block the CsA-induced epithelialto-mesenchymal transition in HK-2 cells probably by suppressing the expression of OPN.     

低蛋白饮食对环孢素A肾病大鼠肾间质纤维化的作用

Objective To investigate whether low-protein diet has protective effect on the progression of renal interstitial fibrosis in rats with cyclosporine A (CsA)-induced nephropathy. Methods Eighteen male Sprague-Dawley rats were randomly divided into three groups (6 rats in each group). The rats in control group (C group) received common diet; in model group (M group) low-salt diet; in intervention group (Ⅰ group) low-salt and low-protein diet. After diet adaptation period of one week, the rats in C group received subcutaneous injection of olive oil 1 mg/kg daily for 5 weeks, while M group and Ⅰ group subcutaneous injection of CsA (diluted into 25 g/L with olive oil) 1 ml/kg for 5 weeks. All the rats were sacrificed at the end of the 5th week. The food-intake and body weight were measured daily. The creatinine clearance (Ccr) was examined before rats were sacrificed. The semi-quantitative pathological analysis on kidney sections was performed. The mRNA and protein expression of transforming growth factor-β1 (TGF-βI) and type Ⅰ collagen (Col Ⅰ) in kidney tissue was determined with real time PCR and immunohistochemical staining, respectively. Results The food-intake and body weight of rats in M and I groups were significantly lower than those in C group (P<0.05). Compared with C group, the Ccr levels in M and Ⅰ groups were significantly reduced [(0.65±0.15) ml/min, (0.40+0.13) ml/min vs (1.55±0.29) ml/min, P<0.05], the relative fibrosis areas of kidney interstitium in M and I groups were significantly increased (3.60%±0.46%, 3.26%±0.75% vs 0.44%±0.24%, P<0.05), the mRNA and protein expression of TGF-β1 in M and I group was significantly up-regulated (by 2.6 and 3.1 times in mRNA and by 1.5 and 1.6 times in protein, respectively, P<0.05), and the mRNA and protein expression of Col Ⅰ in M and I groups was also significantly up-regulated (by 3.0 and 3.5 times in mRNA and by 2.3 and 2.1 times in protein, respectively, P<0.05). There were no significant differences between M and I groups in every parameters above-mentioned except the rat body weight and Ccr. Both the body weight and Ccr in Ⅰ group were significantly lower than those in M group (P<0.05). Compared with C group, the urine osmotic pressure in M group and in I group were deceased (for M group, P>0.05; for I group, P<0.05). Compared with C group, the serum cholesterol levels in M and I groups were significantly increased (P<0.05), and the serum phosphorus level in I group was significantly decreased (P<0.05). The levels of serum albumin and serum calcium of all three groups had no statistical differences (P>0.05). Conclusion Low-protein diet has no renoprutective effects on the rat model of cyclosporin A nephropathy, on the contrary, may induce body weight loss.     

肾移植患者术后早期应用霉酚酸酯的临床观察

目的 观察肾移植术后早期不同剂量霉酚酸酯（ＭＭＦ）与环孢素Ａ（ＣｓＡ）和泼尼松（Ｐｒｅｄ）联用预防急性排斥反应的效果及安全性。方法 将６４例肾移植患者分为３组,分别给予ＭＭＦ２．０ｇ／ｄ（Ａ组）、１．５ｇ／ｄ（Ｂ组）及Ａｚａ ５０～１００ｍｇ／ｄ（Ｃ组）,每组均联用ＣｓＡ及Ｐｒｅｄ（剂量相同）。观察肾移植术后６个月内急性排斥反应的发生率、移植肾功能及药物的副作用。结果 Ａ、Ｂ、Ｃ组急性排斥反应的发     

普乐可复预防同种肾移植排斥反应的研究

目的 评价并比较新型免疫抑制普乐可复（ＦＫ５０６）对预防同种肾移植受者排斥反应的疗效及安全性。方法 随机将９８例肾移植受者分成２组。（１）ＦＫ５０６组（ｎ＝４０）;主要用药为ＦＫ５０６＋霉酚酸酯（ＭＭＦ）＋泼尼松（Ｐｒｅｄ）;（２）环孢素９Ａ（ＣｓＡ组）（ｎ＝５８）;主要用药为;ＣｓＡ＋ＭＭＦ＋Ｐｒｅｄ。结果 ２组受者平均随访时间为１２．５个月。     

The efficacy and safety of high-dose mizoribine in ABO-incompatible kidney transplantation using anti-CD20 and anti-CD25 antibody without splenectomy treatment

Background

Mizoribine (MZR) has been developed as an immunosuppressive agent in Japan, but it shows less potent immunosuppressive effects at doses up to 3 mg/kg/d. In this study, we investigated whether high-dose MZR (6 mg/kg/d) was effective for ABO-incompatible (ABO-i) living donor kidney transplantation (LKT) using treatment with anti-CD25 and anti-CD20 monoclonal antibodies without splenectomy.

Methods

Since 2007, we encountered 24 cases of ABO-i LKT using anti-CD20 and anti-CD25 monoclonal antibody without splenectomy. The pretransplant immunosuppressive regimen consisted of two doses of anti-CD20 antibody, mycophenolate mofetil (MMF), prednisolone, a calcineurin inhibitor (cyclosporine [7 mg/kg] or tacrolimus [0.2 mg/kg] and two doses of anti-CD25 antibody. Antibody removal by plasmapheresis was performed before LKT up to several times according to the antibody titer. The posttransplant regimen consisted of high-dose mizoribine (6 mg/kg/d) instead of MMF (MZR group, n = 12).

Results

The 1-year graft survival rates for the MZR and MMF groups were both 100%. The rejection rate in the MZR group (eight %) was not significantly higher than that in the MMF group (seventeen %) Serum creatinine level was not significantly different between the two groups. In the MZR group 6 (50%) patients developed CMV antigenemia-positivity versus 11 (92%) in the MMF group (P < .05). The number of patients who developed CMV disease was 0 in the MZR group and 1 (8%) in the MMF group. The number of patients treated with ganciclovir was 0% and 8%, respectively (not significant).

Conclusions

We obtain good clinical results with high-dose MZR in ABO-i LKT using anti-CD20 and anti-CD25 antibody treatment without splenectomy.     

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.     

Comparison of Mizoribine and Mycophenolate Mofetil With a Tacrolimus-Based Immunosuppressive Regimen in Living-Donor Kidney Transplantation Recipients: A Retrospective Study in China

Background

A retrospective study was conducted to investigate the prevalence of gastrointestinal (GI) symptoms as well as the efficacy and safety of mizoribine (MZR) and mycophenolate mofetil (MMF) in Chinese living-donor kidney transplantation (LDKT).

Randomized comparative trial of mizoribine versus mycophenolate mofetil in combination with tacrolimus for living donor renal transplantation

Background

Mizoribine (MZR) was approved in 1984 in Japan for the suppression of rejection in renal transplantation with an approved administration dosage of 1–3 mg/kg/day. The action of MZR resembles that of mycophenolate mofetil (MMF), but MZR dosing is markedly lower than that of MMF. To examine whether higher dosing of MZR could obtain efficacy similar to MMF in renal transplantation, we conducted a comparative study of MZR and MMF using a high daily dose of MZR.

Methods

A prospective, randomized comparative study of MZR versus MMF using tacrolimus (FK) and steroids as the base was conducted in 35 patients who had undergone living-donor renal transplantation (ABO-incompatible patients were not included) at 8 institutions in Japan between July 2005 and June 2007. Starting doses were 12 mg/kg/day for MZR and 2 g/day for MMF. Dosages of FK and steroids were set according to the protocol of each institution.

Results

Patient and graft survival rate at 1 year after transplantation was 100 % in each group, with no significant difference in rejection rate apparent between groups. Adverse events found in both groups were characteristic, frequently involving infection and digestive organ disorder in the MMF group and elevated uric acid levels in the MZR group.

Conclusions

Based on these results, MZR and MMF are considered almost equivalent in terms of efficacy and safety.     

Infectious complications in geriatric renal transplant patients: comparison of two immunosuppressive protocols

BACKGROUND: It has been well documented that a regimen of mycophenolate mofetil (MMF), cyclosporine (CsA), and prednisone (Pred) reduces the incidence of acute rejection in renal transplant recipients, as compared with previous regimens based on azathioprine (AZA), CsA, and Pred. In the general renal transplant patient population, immunosuppressive regimens that include MMF are usually well tolerated. It is not clear whether this holds true for older transplant recipients, who may be more susceptible to complications from the greater immunosuppression conferred by MMF. METHODS: We retrospectively analyzed our geriatric renal transplant population (age >60 years, 1990-1998) and compared a cohort of 46 patients treated with AZA, Pred, and CsA to a cohort of 45 patients treated with MMF, Pred, and CsA. RESULTS: There were no significant differences between the groups with regard to pretransplantation demographics. Patient and graft survival during the first year was not significantly different between the groups. During the first year of follow-up, we observed 27 infections requiring hospitalization in 15 patients in the MMF-treated group as compared with 10 infections in 7 patients in the AZA-treated group. A Cox proportional hazard model accounting for the above mentioned covariates isolated MMF versus AZA as a significant risk factor for the occurrence of serious infectious events (all: P<0.01; cytomegalovirus, fungal: P<0.01). CONCLUSION: We conclude that an immunosuppressive regimen of MMF, CsA, and Pred seems to be correlated with an increased incidence of infectious adverse events as compared with AZA, CsA, and Pred in elderly patients.     

Studies on the multiple-drug induction immunosuppressive therapies with cyclosporine after renal transplantation

Our induction immunosuppressive therapies were carried out on patients split into three groups. The first group of 25 recipients were treated with regimen I [cyclosporin (CsA); 12 mg/kg/day and prednisolone (Pred)]. The second group of 16 recipients were treated with regimen II [CsA; 6 mg/kg/day, Pred and mizoribine (MIZ) or azathioprine (AZA)]. The third group of 14 recipients were treated with regimen III [CsA; 10 mg/kg/day, Pred and MIZ or AZA]. There was no significant difference among the three groups in renal function three months after renal transplantation. The frequency and grade of rejection were significantly higher in Group II than in the other groups. One of group I had CsA nephrotoxicity and none of group III had liver dysfunction three months after renal transplantation. Group I had a higher incidence of posttransplant hypertension. Hypertension of group I was very severe. We concluded that the triple-drug therapy on group III was the best induction immunosuppressive therapy after renal transplantation of the above three.     

骁悉、环孢素A和泼尼松在肾移植受者联合应用中最适剂量探讨

目的探讨国人肾移植后骁悉(MMF)、环孢素A(CsA)和泼尼松(Pred)联合应用的最适剂量。方法比较常规剂量组(104例)和低剂量组(96例)患者肾移植术后免疫抑制剂用量和急性排斥反应、肺部感染发生率和人/移植肾生存率。结果MMF和CsA用量在术后3个月、Pred用量在术后6个月内常规剂量组明显高于低剂量组。常规剂量组在6个月内包括活检证实、临床推断和亚临床排斥,其总的急性排斥发生率为17.3%,而低剂量组为19.8%,两组间差异无显著性意义(P=0.55)。两组患者在6个月内肺部感染发生率分别为40.4%和11.5%(P<0.0001),尤其是重症肺部感染发生率常规剂量组明显要高(26.9%比5.2%,P<0.0001)。两组患者人/肾1年生存率分别为87.4%/85.5%和97.9%/96.9%(P均<0.01)。排除感染所致的带功死亡后两组患者人/肾1年生存率差异无显著性意义。结论低剂量MMF、CsA和Pred联合应用并不增加急性排斥率、亚临床排斥发生率、排斥治疗逆转率和排斥反应的严重程度,但明显降低肺部感染发生率和病死率。     

用于肾移植的几种免疫抑制方案的对比研究

目的 比较肾移植后几种常用免疫抑制治疗方案的疗效与副作用。方法 根据所使用的免疫抑制治疗方案将８７例肾移植患者分为４组,Ａ组的免疫抑制治疗方案为他克莫司（ＦＫ５０６）、霉酚酸酯（ＭＭＦ）和泼尼松（Ｐｒｅｄ）;Ｂ线为环孢素Ａ（ＣｓＡ）、ＭＭＦ和Ｐｒｅｄ;Ｃ组为ＣｓＡ、硫唑嘌呤（Ａｚａ）和Ｐｒｅｄ;Ｄ组为ＣｓＡ和Ｐｒｅｄ。观察术后移植肾功能的恢复情况、排斥反应发生率、并发症及免疫抑制剂用量的变化。结果