公民逝世后器官捐献供肾评估方法及改善的研究进展

公民逝世后器官捐献正逐渐成为我国器官移植的主要器官来源。公民逝世后器官捐献供肾受多种不稳定因素影响,其质量不能得到有效的保障,导致公民逝世后器官捐献移植肾术后原发性无功能和移植物功能延迟恢复的发生率较高。因此,提高术前评估水平、改善供肾质量、降低术后早期并发症发生率是公民逝世后器官捐献肾移植重点要解决的问题。本文针对目前公民逝世后器官捐献供肾的两种常用评估方法——术前供肾活组织检查和机械灌注,及改善供肾质量的方法——体外膜肺氧合(ECMO)进行述评,介绍其研究进展。     

他克莫司对肾移植受者外周血NK和NKT细胞比例的影响及临床意义

他克莫司(Tacrolimus)是一种强效免疫抑制剂,现已广泛应用于肾脏、肝脏及心脏移植,有效减低了排异反应的发生,提高了移植受者的存活率.但是他克莫司个体药代动力学差异大,不同个体对其血药浓度的敏感性及耐受性有差异,故单纯依靠血药浓度监测不能有效反映移植受者的免疫状态.因此如何了解移植受者的免疫状态,指导免疫抑制剂的个体化应用,在免疫抑制不足及免疫过度之间寻找平衡,成为困扰移植医生的问题.NK细胞(natrural killer cell)是天然免疫系统的主要效应细胞.     

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.     

华东制药产他克莫司在临床肾移植中的应用

目的 评估中美华东制药有限公司生产的他克莫司胶囊(赛氏Tac胶囊)在临床肾移植中应用的有效性及安全性.方法 采取多中心、随机开放性、前瞻性临床研究,按照入选标准和排除标准,来自9个移植中心的共计65例肾移植受者入选.人选受者的年龄为(36.53±5.71)岁,8例为亲属活体供肾,供肾冷缺血时间为(4.08±5.43)h,热缺血时间为(3.90±2.15)min,供、受者HLA抗原错配数为(2.1±0.8)个.受者肾移植后采用赛氏Tac胶囊+吗替麦考酚酯+皮质激素预防排斥反应,移植后48 h内给药,Tac的起始剂量为0.1～0.15 mg·kg-1·d-1,术后60 d内维持血Tac浓度谷值在8～12μg/L,之后维持在5～10μg/L,直至观察终点(术后12周).监测12周的治疗结果,并进行有效性和安全性的评价.主要有效性终点为发生经病理证实的急性排斥反应,次要有效性终点为移植肾或受者的存活情况以及肾功能(以血清肌酐水平评价).安全性评价指标为研究期间发生的感染、肝功能损害、高血压、高血脂、糖尿病、多毛或痤疮等不良反应.结果术后第1、2、4、8和12周的Tac用量分别为(6.54±1.69)、(6.39±1.45)、(6.73±1.25)、(6.25±1.02)和(6.03±1.16)mg,对应的血药浓度谷值分别为(8.24±2.09)、(9.39±1.35)、(9.93±1.87)、(7.23±1.16)和(6.43±1.26)μg/L.观察期内经活检证实的急性排斥反应发生率为12.3%(8/65),6例经冲击治疗逆转,移植肾存活率为96.9%(63/65).研究期内受者的肺部感染发生率为7.6%,肝功能异常发生率为7.7%,高血压发生率为7.7%,高血脂发生率为4.6%,糖尿病发生率为4.6%.结论 赛氏Tac胶囊用于肾移植受者是安全、有效的.

Abstract：

Objective To demonstrate the efficacy and safety of Hangzhou tacrolimus capsule(Saishi Tac capsule, Hangzhou Zhongmei Huadong Pharmaceutical Co. Ltd, China) in Chinese kidney transplant recipients. Methods Multicenter, randomized open-labeled, prospective controlled clinical trial was performed in de novo Chinese kidney transplant recipients. According to including and excluding criterions, 65 kidney recipients from 9 transplant centers were enrolled. The mean age of recipients was (36.53 ± 5.71 ) years, and 8 received living donor transplantion. The time of cold ischemia and warm ischemia was (4.08 ± 5.43) h and (3.90 ± 2.15) min respectively. The number of mismatched HLA was (2.1 ± 0.8). The recipients accepted Saishi Tac capsule + mycophenolate steroid 60 days, followed by 5-10 μg/L until the terminal observation time point (12 weeks after transplantation). The efficacy and safety were estimated during the period. The primary efficacy endpoint of the study was the incidence of biopsy-confirmed acute rejection. Graft survival and renal function (evaluated by serum creatinine) were the secondary endpoints. Safety was assessed by monitoring laboratory parameters and adverse events reported over the course of the study, such as infection, hepatic damage, hypertension, hyperlipema, diabetes mellitus and other adverse affairs.Results The dose of Tac at 1 st, 2nd, 4th and 8th week postoperation was (6.54 ± 1.69), (6.39 ±1.45),(6.73± 1.25), (6.25 ± 1.02) and (6.03 ± 1.16) mg, corresponding values to the C0 were (8.24±2.09),(9.39± 1.35),(9.93± 1.87),(7.23± 1.16) and (6.43± 1.26) μg/L. During 12weeks of follow-up, the incidence of biopsy-confirmed acute rejection was 12.3% (8/65), among which 6 cases were reversed by implosive therapy. The survival rate of graft kidney was 96.9% (63/65). The incidence of hypertension and hepatic damage was both 7.7% and morbidity of lung infection was 7.6%. There were 3 patients (4.6%) complicated with hyperlipema and diabetes mellitus respectively. Conclusion During the first 3 months of treatment Saishi Tac capsule was safe and effective to Chinese kidney transplant recipients.     

98例肾移植受者术后肺部感染的临床分析

目的分析肾移植术后肺部感染发病及治疗特点。方法回顾性分析98例。肾移植术后肺部感染患者临床资料。结果肾移植术后肺部感染发生率为14．96％,术后3个月以巨细胞病毒为主,3个月以上以细菌为主。治愈率为79．59％,死亡率为20．41％,混合感染的治愈率较其他感染低（P〈0．05）,死亡率较其他感染高（P〈0．05）。结论肾移植后肺部感染发生率较高,早期诊断、抗感染及调整免疫方案是关键。     

冷冻保存后成人胰岛细胞与小肠黏膜下层的共培养

目的:探讨猪小肠黏膜下层(SIS)对冷冻保存后的胰岛细胞的支持和保护作用．方法:分离纯化后的成人胰岛细胞经冷冻保存1 mo后分为 SIS组和对照组,在RPMI-1640培养液培养1 wk后分别测定两组的胰岛细胞回收率,观察胰岛细胞形态并进行胰岛素刺激释放试验．结果:SIS组胰岛细胞回收率为90．5±1．8％,较游离组62．7± 3．6％显著提高(P<0．05),胰岛形态较对照组完整．在高糖刺激下,SIS组胰岛素分泌量较游离组增高(25．8±1．7 mU／L vs 14．6±1．3 mU／L,P<0．05)．在含有茶碱的高糖溶液中,微囊组的刺激指数为游离组的3倍．结论:SIS作为一种天然的细胞外基质材料,可显著提高胰岛细胞冷冻保存后的回收率,并改善胰岛细胞的功能．     

肾移植患者最适免疫抑制状态的初步探讨

近年来，随着组织配型及强力免疫抑制药物的临床应用，人／肾存活率逐年升高，肾移植已成为临床治疗肾功能衰竭的主要方法，但移植术后患者面临的主要问题也日益突出，免疫抑制不足所致排斥反应和免疫抑制过度所致的感染成为影响移植后长期存活率的主要原因。因此，探讨移植术后患者最适免疫抑制状态成为当务之急。CD15s是选择素配体的一种，可与3种选择素（Selectin P、E和L）结合，主要为选择素E和P识别，其作用是使白细胞黏附到内皮细胞及血小板上。静止的T、B淋巴细胞被抗原激活才表达CD15s，因此可通过检测外周血淋巴细胞表面的CD15s抗原表达来了解机体的免疫状态。     

肾移植术后并发结核感染18例临床分析

目的：探讨肾移植术后并发结核感染的临床特点、诊断及治疗经验。方法：回顾性分析18例肾移植术后并发结核感染患者的临床资料。结果：肾移植术后并发结核感染率为1.3%(18/1402)，临床上以肺结核多见，本组中肺结核15例，颈椎结核1例，颈淋巴结结核1例，移植肾结核1例，诊断主要依靠X线照片和B超检查。全组治愈14例（78％），死亡4例（22％）。治愈病例中5例曾合并肺部细菌、真菌和巨细胞病毒混合感染，4例发生移植肾排斥反应。不良反应主要是肝功能异常，经减少环孢素剂量，相应增加霉酚酸酯剂量，同时予护肝治疗后肝功能恢复正常。结论：肾移植术后结核感染的发生率高于正常人群，且常合并真菌和巨细胞病毒混合感染及移植肾排斥反应，治疗过程易发生肝功能损害，应予高度重视。     

肾移植术后三种白细胞介素的监测及其意义

１９９２年９月～１９９５年１２月监测了１３２例肾移植患者术后白细胞介素（ＩＬ）２、ｓＩＬ２Ｒ和ＩＬ６的变化，以探讨肾移植术后免疫功能的变化规律，及在诊治急性排斥和继发感染中的意义。一、资料和方法１临床资料。本组１３２例肾移植术后患者，男７８例...