雷帕霉素联合小剂量环孢素在肾移植受者转换治疗后的2年临床观察

目的探讨肾移植术后由经典环孢素(CsA)三联免疫抑制治疗转换为雷帕霉素(SRL)联合小剂量CsA和强的松(Pred)的临床有效性和安全性。方法对46例口服CsA+霉酚酸酯(MMF)+Pred的肾移植受者,进行SRL+小剂量CsA+Pred的转换治疗。其中主动转换组27例(转换前血肌酐Scr<140μmol/L,无或仅轻微蛋白尿),被动转换组19例(Scr>140μmol/L,蛋白尿<2+)。转换后目标谷浓度SRL 4～7 ng/ml,CsA 20～50 ng/ml。观察转换后2年的Scr、eGFR和尿蛋白变化,并动态监测PRA水平,急性排斥反应发生率以及雷帕霉素相关的不良反应。结果转换后所有受者CsA平均减药量超过60%。转换后3月时,主动转换组Scr由转换前平均(109±27)μmol/L下降至(97±19)μmol/L(P<0.01),eGFR由平均63±11上升至(71±12)ml/min/1.73 m2(P<0.01),并在平均随访2年期间保持平稳,尿蛋白仅1例出现明显加重。被动转换组中共10例在随访期间退组,其中8例退组原因为发展至肾功能不全或蛋白尿加重,其余组内受者Scr由转换前平均(195±43)μmol/L下降至(165±39)μmol/L(转换后3月,P<0.05),eGFR由平均33±8上升至(41±15)ml/min/1.73 m2(转换后3月,P<0.05),并一直维持平稳。两组病例中,基础PRA阴性的受者中95%保持阴性,基础PRA阳性的受者中60%在转换后的随访期间明显下降,其余40%的PRA无增加。2年随访期内无1例急性排斥反应发生。绝大多数病例未见明显的雷帕霉素副作用。结论 SRL联合小剂量CsA的转换治疗在平均2年的临床观察期内能总体改善移植肾功能、有效预防急性排斥反应,可能是一种既能显著减轻CsA肾毒性又经济实用的较理想免疫抑制方案。但需把握好转换的适应症,对已有明显蛋白尿或慢性肾功能不全受者需谨慎转换。     

雷帕霉素在儿童肾移植中的临床应用

目的:探讨雷帕霉素在儿童肾移植中的临床应用,以期提高肾移植效果.方法:对13例术后应用雷帕霉素的9～18岁的儿童肾移植资料进行回顾性分析.结果:13例患者术后随访5～26个月,平均16.7个月,人、肾存活率为100%.术后3例发生急性排斥反应,经甲基强的松龙冲击治疗后逆转;1例发生急性肾小管坏死;1例发生慢性排斥反应;高脂血症4例;肺部感染5例;肝功能损害2例;贫血1例.结论:儿童肾移植术后,应用雷帕霉素是安全有效的.     

雷帕霉素对肾移植患者术后肾功能的影响

目的探讨国产雷帕霉素(rapamycin,RPM)联合环孢菌素A(cyclosporineA,CsA)、激素(steroid,ST)对肾移植患者术后肾功能的影响。方法本实验为随机开放、与硫唑嘌呤(azathioprine,AZA)平行对照的多中心Ⅱ期临床研究,观察期24周;172例首次接受同种异体肾移植的患者术后72小时内随机平均分配进入两组:RPM组,应用RPM、CsA和ST;AZA组,应用AZA、CsA和ST。对术后24周内的肾功能指标[肌酐(SCr)、尿素氮(BUN)、尿酸(UA)以及肾功能首次恢复时间]和相关的不良事件进行客观评价。结果与AZA组术后肾功能首次恢复时间(23.63±39.24)天相比,RPM组术后肾功能首次恢复时间(17.05±36.31)天更早。术后24周,RPM组和AZA组的SCr分别为(93.75±26.40)μmol/Lvs(102.39±44.61)μmol/L,P=0.145;BUN分别为(6.16±1.68)mmol/Lvs(7.05±1.56)mmol/L,P=0.001;UA分别为(329.09±76.25)mmol/Lvs(360.06±74.82)mmol/L,P=0.013,各项肾功能试验室指标RPM组均低于AZA组。发生肾功能相关的不良事件,RPM组7例(8.14%),AZA组18例(20.93%),其中高尿酸血症AZA组多于RPM组(17例,19.77%vs3例,3.49%),P=0.001。结论RPM、CsA和Pred联合应用于同种肾移植,更有利于术后移植肾功能的恢复,且无肾毒性。     

免疫抑制剂在肾移植中的应用

目的:探讨免疫抑制剂在肾移植急性排斥反应中的作用和安全性.方法:应用计算机检索2000-01/2009-10维普数据库和清华同方数据库.以"肾移植、免疫抑制剂、霉酚酸酯、他克莫司、环孢素、雷帕霉素、抗CD25单克隆抗体、抗CD3单克隆抗体"为检索词.文章所述内容应与免疫抑制剂预防、治疗肾移植术后急性排斥反应的研究相关.结果:肾移植应用免疫抑制剂可以降低急性排斥发生率,使得移植肾短期存活明显改善,免疫抑制剂的肾毒性仍然是制约移植肾长期存活的重要因素.近年来出现新型免疫移植剂如雷帕霉素、FFY720等使得移植肾的长期存活成为可能.新型免疫抑制方案应着重减少毒副反应而不是单纯降低排斥反应发生率.结论:随着近年来对移植免疫认识的深入,在免疫抑制剂上取得了很大的进步,给临床医生提供了越来越多的选择,但是令人满意的免疫抑制剂和免疫抑制方案还需不断探索.     

雷帕霉素浓度检测在慢性移植肾功能损害中的应用

目的：分析探讨雷帕霉素浓度检测在移植肾慢性肾功能损害中的临床意义。方法收集2009年1月至2012年6月肾移植后出现慢性肾功能损害并加用雷帕霉素治疗的患者78例,其中男58例,女20例,年龄20～68岁,应用 Syva Emit-2000药物浓度检测分析仪,采用酶免疫放大技术检测雷帕霉素血药谷值浓度,并统计患者治疗前、后血肌酐变化情况。所有病例免疫抑制剂治疗方案均采用雷帕霉素（RPM）联合小剂量他克莫司和霉酚酸酯、强的松四联用药方案。结果78例患者共检测雷帕血药谷浓度488例次,单人检测最少3例次,最多20例次。血药谷浓度范围（2．9～13．2）ng/mL,平均（5．83±2．21）ng/mL。其中50例患者血肌酐水平由联合用药前的（206．2±76．65）μmol/L 降至（141．16±63．56）μmol/L,差异有统计学意义（P ＜0．01）。10例患者联合用药血肌酐值稳定没有继续升高。本组服用雷帕霉素患者出现不良反应蛋白尿和高脂血症发生率分别为34．6％和21．7％。结论雷帕霉素的浓度存在着较大的个体间差异,只有及时、定期的进行血药浓度动态监测,才能帮助临床医生更好地判断疗效,调整用药剂量,最低限度的降低药物不良反的发生,较好的控制并改善移植肾功能,提高人/肾存活率。     

肾移植术后雷帕霉素为基础的免疫抑制剂治疗中环孢素A保留和撤除的近期及远期有效性和安全性评价

目的评价雷帕霉素为基础免疫抑制剂治疗中CsA保留与撤除近期与远期有效性和安全性。方法采用Cochrane系统评价方法,计算机检索MEDLINE、EMBASE、Cochrane图书馆临床对照试验数据库(CENTRAL)、CNKI等数据库,检索时间从1995年1月至2005年12月。纳入以雷帕霉素为基础免疫抑制剂治疗中CsA保留与撤除近期与远期有效性和安全性的随机对照试验。由2名评价者共同评价纳入研究的质量,对同质研究采用Rev-Man4.2.7软件进行Meta分析。结果共纳入10个研究,肾移植术后患者1121例。纳入研究根据随机方法、分配隐藏和盲法描述评分,6个为A级,4个为B级。Meta分析结果显示,CsA撤除对患者生存率的OR(95%CI)值在6、12、24、36个月的分别为0.77(0.17,3.52)、1.24(0.48,3.16)、1.32(0.57,3.08)、1.21(0.60,2.41);移植肾存活率的OR(95%CI)值在6、12、24、36、48、54个月时分别为1.79(0.63,5.06)、1.15(0.56,2.36)、1.39(0.68,2.85)、1.80(0.99,3.29)、2.13(1.16,3.89)、2.01(1.15,3.51);急性排除反应在6、12、24、36、48个月的OR(95%CI)值分别为0.92(0.48,1.78)、1.90(1.25,2.89)、2.01(0.94,4.27)、1.93(0.93,4.00)、1.52(0.77,3.02)。结论现有研究结果显示,肾移植术后病情稳定患者,以雷帕霉素为基础的免疫抑制剂治疗中,CsA撤除在第1年易导致急性排斥反应发生,但是对于人长期生存率无影响,同时有助于移植肾长期存活、肾功能恢复。由于纳入研究存在选择性偏倚和测量性偏倚的高度可能性,势必影响结果的证据强度,期待高质量的随机双盲对照试验提供高质量的证据。     

雷帕霉素在血液病中的应用

大环内酯类抗真菌抗生素雷帕霉素(RAPA)有强效免疫抑制和抗细胞增殖活性,国内外已广泛用于肾、心、肝等实体器官移植后急性排斥反应的防治,因无肾毒性而优于环孢素A。RAPA主要抑制细胞增殖、生存信号Ras/PI3k/Akt途径下游哺乳类雷帕霉素靶蛋白(mTOR),使细胞增殖周期停滞在G1期而凋亡,主要副作用为高脂血症。临床上已用于治疗骨髓增生异常综合征和急性白血病等。本文简述RAPA的药物动力学、毒副作用和作用机制,并指出RAPA用于防治造血干细胞移植后移植物抗宿主病(GVHD)、恶性血液病和免疫性疾病可能有较好的临床应用前景。     

雷帕霉素在肾移植中的应用

我院2003-01～2003—06雷帕毒素在肾移植中应用30例，效果较好。总结如下。     

肾移植后急性排斥反应及免疫抑制剂的应用

背景：肾移植后急性排斥反应在临床较为常见,免疫抑制剂的出现促进和推动了肾移植质量的提高,免疫抑制剂的合理应用对肾移植患者至关重要,成为影响患者生存率的重要因素。目的：对肾移植后急性排斥反应和免疫抑制剂研究文献进行多层次分析。方法：以电子检索方式对Web of Science数据库2002至2011年收录肾移植后急性排斥反应和免疫抑制剂研究的文献进行分析,采用检索词为＂肾移植;急性排斥反应;免疫抑制剂＂。对肾移植后排斥反应进行分类,了解肾移植后免疫抑制剂的种类,分析各种免疫抑制剂的特点。结果与结论：Web of Science数据库2002至2011年收录肾移植后急性排斥反应和免疫抑制剂研究的文献共6105篇,文献数量总体呈现出逐步上升的发展状态,《移植学会会报》杂志是发表肾移植后急性排斥反应和免疫抑制剂研究文献较多的期刊。美国在此类研究中发表文献最多,其次为德国。收录文献按被引频次由高到低排序前10位中,有4篇来源于《新英格兰医学》杂志。中国在过去10年间被收录文章总量排在第9名,共发表238篇相关文献,中国的国家自然科学基金资助文献有17篇。     

免疫抑制剂在肾移植中的应用进展

免疫抑制剂的应用使得移植肾短期存活明显改善,免疫抑制剂的肾毒性(如钙调免疫抑制剂)仍然是制约移植肾长期存活的重要因素.近年来出现新型免疫移植剂如雷帕霉素、FTY720等,及新型免疫抑制方案如低剂量、无激素及无钙调免疫抑制方案等使得移植肾的长期存活成为可能.本文就免疫抑制剂在肾移植中的应用进展作一概述.     

Gastrointestinal carcinomas in renal transplant recipients

The development of malignancies in renal transplant recipients is well documented. Typically, these are cutaneous tumors or lymphomas. During the past 5 years, we have encountered six patients with documented carcinomas of the gastrointestinal tract, which developed after these patients received renal transplants. These carcinomas developed at an average of 10 years (range 2–16 years) after renal transplantation. There were three carcinomas of the colon, and one each of the esophagus, stomach, and anal canal. In many instances, the patients had examinations prior to transplantation which were normal. Several surveys of transplant recipients indicate there is an increased incidence of gastrointestinal tract malignancies after transplantation. These studies also recommend that screening of the gastrointestinal tract in long-term transplant recipients be performed. Since these patients are often imaged in the radiology department, radiologists must be aware of this possible complication.     

Virus infections in renal transplant recipients.

534 serum samples from 73 renal transplant recipients, 41 haemodialysis patients, and 99 blood and organ donors were examined serologically for antibodies against Cytomegalo, H. simplex (types 1 and 2), Varicella-zoster, Epstein-Barr, Adeno, Influenza, Parainfluenza, Respiratory syncytial, Measles, Picorna- and human Polyoma- Viruses. Serum specimens were stored in the lyophilized state until examined thus enabling a simultaneous testing of all samples belonging to one patient. All antigens, complement, and control antisera were prepared, lyophilized, and standardized in this laboratory. This has enabled the use of single batches of any preparation throughout the study. Serologic results with antigens of the Herpesvirus group (CMV, HSV and VZV) compared favourably with previous results showing that infections with these agents, especially with CMV, can frequently be encountered among transplant recipients. Our results have indicated a moderately increased incidence of infections with some Herpesviruses in haemodialysis patients as well. Infections with VZV, for instance, were as frequently demonstrated in these patients, as in transplant patients although the former received no immunosuppressive therapy. Serologic results with non-Herpesvirus antigens indicated an increased incidence of infections with Polyomavirus, Myxoviruses (Influenza, Parainfluenza and RS) and Picornaviruses among transplant recipients. The incidence of acute infections with RS virus among adults was unusually high and there is no evidence so far to indicate such a high frequency of RS infections in any other group of adults. We were unable to demonstrate acute infections with non-Herpesviruses among haemodialysis patients, even though most of the patients were followed over a period of more than 2 years. Virus isolation attempts were performed with samples of urines and biopsy or autopsy samples. 23 out of 28 cytopathic agents recovered from urines, throat-swabs and/or from organs of transplant recipients were identified as CMV. Two HSV type 1, 1 HSV type 2, and 2 Coxsackie B type 3 viruses were also isolated. No viruses were isolated from a series of 31 kidneys randomly selected among autopsy cases.     

Telmisartan pharmacokinetics in Japanese renal transplant recipients

BACKGROUND: Telmisartan is taken up into human hepatocytes by organic anion-transporting polypeptide (OATP/gene SLCO) and is glucuronized by uridine diphosphate-glucuronosyltransferases (UGTs) into the acylglucuronide, and it is then excreted by transporters such as multidrug resistance 1 (MDR1/gene ABCB1), multidrug resistance protein 2 (MRP2/gene ABCC2), or breast cancer resistance protein (BCRP/gene ABCG2). We elucidated the association of UGTs (1A1, 1A6, 1A7, 1A9 and 2B7), SLCOs (1B1, 1B3 and 2B1), ABCB1, ABCC2 and ABCG2 polymorphisms with steady-state telmisartan pharmacokinetics in 12 Japanese renal transplant recipients. METHODS: Recipients were given 40 mg of telmisartan for at least 6 months. Blood was sampled 1 y after transplantation. Plasma concentrations of telmisartan were measured by HPLC. RESULTS: In subjects with the ABCC2 -24C/T genotype, the maximum plasma concentration of telmisartan was significantly greater than that in C/C genotype (96.8 vs. 57.4 ng/ml, respectively, P=0.0094). In ABCC2 -24C/C, the second peak plasma concentration of telmisartan was observed 13 h after oral administration, but not ABCC2 -24C/T genotype group. There was no significant difference in the telmisartan pharmacokinetics between genotype groups of other transporters such as SLCO1B3, ABCB1 and ABCG2 or UGTs. CONCLUSIONS: ABCC2 genetic polymorphisms appear to strongly influence inter-individual variation of telmisartan pharmacokinetics. MRP2 may be predominantly involved in the telmisartan pharmacokinetics in humans.     

肾移植术后性功能调查情况分析

目的 探讨肾移植后病人的性功能状况。方法 对肾移植成功后存活3个月以上患者21例,进行性功能状况调查。结果 移植术后性功能明显改善。结论 成功的肾移植是使慢性肾衰患者重新获得性功能的最有效的治疗手段。     

Urinary tract infection in renal transplant recipients

Urinary tract infection (UTI) is common in renal transplant recipients. Frequency of UTIs depend on many factors such as age, female gender, kidney function, co-morbidity, type and amount of immunosuppression, urological instrumentation and/or the follow-up period (short term or long term) after kidney transplantation. UTI may worsen graft and patient survival. A significant proportion of renal transplant recipients with UTIs may develop acute pyelonephritis (APN), which is an independent risk factor for deterioration of graft function. Renal transplant recipients with UTIs are often clinically asymptomatic as a consequence of immunosuppression. UTI, however, may progress to APN (particularly in the early post-transplant period), bacteraemia and the full blown picture of urosepsis. Strategies for long term prophylaxis and antimicrobial treatment of UTI in renal transplant recipients are discussed.     

Diltiazem use in tacrolimus-treated renal transplant recipients

BACKGROUND: Calcium channel blockers are widely used in the treatment of post-transplant hypertension but have the potential for drug interaction with calcineurin inhibitors. Renal allograft outcomes when diltiazem is used with cyclosporine have been reported, but similar data with tacrolimus are not available. METHODS: We performed a retrospective analysis of all our renal transplant recipients from March 1997 to March 2002 who were given tacrolimus, mycophenolate mofetil and prednisone. Patients were divided into two groups based on whether diltiazem was started in the first postoperative week. Outcome measures included renal function up to 2 years post-transplant, blood pressure (BP) control, tacrolimus exposure, and costs related to tacrolimus monitoring. RESULTS: Sixty-four patients constituted the diltiazem group and 32 the control group. Their baseline characteristics were similar. The mean average daily dose of diltiazem used was 213.95 mg/day. There was no difference in renal function, graft survival, or patient survival over 2 years. BP control was similar although the diltiazem group required more medication. Diltiazem was discontinued in four patients due to side-effects. There was no difference in tacrolimus-related side-effects between the two groups. There was also no difference in tacrolimus exposure, cost related to tacrolimus monitoring, or combined costs when the expense of diltiazem was added. CONCLUSION: Diltiazem use is acceptably safe and efficacious in renal transplant recipients treated with tacrolimus-based immunosuppressive therapy. It can be considered as a first-line antihypertensive in these patients and is cost neutral for tacrolimus use.     

Stressors in renal transplant recipients at six weeks after transplant

The purpose of this study is to identify stressors that renal transplant recipients report experiencing 6 weeks posttransplantation and compare them with stressors reported by Hayward et al. (1989). The sample consists of 48 adult renal transplant recipients. Stressors are measured by the Kidney Transplant Recipient Stress Scale. The most stressful item identified is the possibility of repeated hospitalizations, different from the Hayward Study in which possibility of rejection was the most frequently reported stressor. Nurses can use this information to better understand the stressors related to the renal transplant experience and to then develop appropriate interventions that can enhance clients' self-care actions.