无血缘夫妻活体供肾7例肾移植

背景：通过诱导移植受体产生供-受体嵌合体或免疫耐受以利于受体长期存活,一直是器官移植的研究热点,并且在实验动物模型中获得了大量成功的经验和知识。在临床实践中也观察到结婚多年的夫妻,丈夫-妻子器官移植后排斥反应小,具有比其他的亲属器官移植有更多的优点。 目的：回顾性分析无血缘关系的活体供肾移植—丈夫对妻子供肾移植的临床效果。 方法：选择7例夫供妻活体肾移植,供者年龄 32~58岁,受者年龄 31~56岁,双方婚龄在5~36年。供、受者 ABO血型完全相同者 4例,O-B 1例,O-A 1例,A-AB型 1例。淋巴细胞毒交叉配合试验阴性。HLA配型情况：1个抗原错配 1例,2个抗原错配 2例,3个抗原错配3例,4抗原错配 1例。开放手术取肾,6例左肾,1例右肾。术后采用三联免疫抑制方案：环孢素A/他克莫司+麦考酚酸吗乙酯+泼尼松预防排斥反应,7对供受者随访3~70个月。 结果与结论：手术成功率100%,供受者均未发生手术相关并发症,所有供者血压、尿常规及肾功正常,受者及移植肾全部存活。验证了虽然移植前组织配型结果较差,但由于夫妻间长期生活在一起产生的免疫耐受,使夫供妻肾移植后排斥反应小、移植效果理想,具有比其他的亲属肾移植有更多的优点。     

亲属活体供肾移植后低剂量钙调蛋白酶抑制剂的应用

背景：亲属活体肾移植供、受者移植前准备充分,供肾热、冷缺血时间较短,HLA配型的组织相容性好,移植后排斥反应发生率低,为亲属活体供肾肾移植后采用低剂量免疫抑制剂方案提供了可能性。 目的：探讨亲属活体供肾移植后低剂量钙调蛋白酶抑制剂的安全性和有效性。 方法：选取2006-01/2008-06在南京医科大学第一附属医院肾移植中心行亲属活体供肾移植的受者38例,移植后常规使用环孢素A/他克莫司+吗替麦考酚酯+泼尼松的三联免疫抑制方案。将38例患者随机分为两组：CNI常规剂量组(n=18),移植后初始药物剂量为环孢素A 6 mg/(kg•d)或他克莫司0.12 mg/(kg•d);CNI低剂量组(n=20),术后初始药物剂量为环孢素A 4 mg/(kg•d)或他克莫司0.08 mg/(kg•d);两组吗替麦考酚酯和泼尼松使用剂量相同。移植后密切随访,比较两组患者移植后不同时期的肾功能以及急性排斥反应、肺部感染、肝功能损害、肾毒性等并发症的发生情况。 结果与结论：随访12个月,CNI常规剂量组重度肺部感染死亡1例,CNI低剂量组无死亡病例。两组移植肾功能及急性排斥反应发生率比较差异均无显著性意义(P > 0.05);CNI低剂量组肝功能损害、钙调蛋白酶抑制剂肾毒性发生率显著低于CNI常规剂量组 (P < 0.05)。此外,采用低剂量钙调蛋白酶抑制剂免疫抑制方案明显减轻了亲属肾移植患者的经济负担。说明亲属活体供肾移植后采用低剂量钙调蛋白酶抑制剂的免疫抑制剂方案安全、有效。     

CRTER关注“肾移植免疫用药”内容

<正>经环孢素A在器官移植中的免疫抑制作用环孢素A和他克莫司对移植肾P-糖蛋白表达的影响:3年随访移植肾活检环孢素A在肾移植后的应用及血药浓度监测分析稳定期肾移植受者微乳化环孢素峰浓度监测     

夫妻活体供肾移植与血缘亲属供肾移植

背景：夫妻间活体肾移植尽管在组织配型方面差于血缘关系供肾移植,但在临床实践观察中夫妻肾移植与血缘关系肾移植间近期疗效并无明显差异。 目的：对比同期实施的夫妻活体供肾移植和血缘亲属供肾移植的临床疗效,总结夫妻活体供肾移植的临床经验。 方法：回顾性分析郑州人民医院实施的夫妻活体供肾移植18例及血缘亲属供肾移植100例的临床资料,通过对两组移植前组织配型情况和移植后(1,3,6个月)肾功能恢复情况,移植肾功能延迟恢及半年内急性排斥反应发生率、感染发生率等指标的分析,对夫妻活体供肾移植和血缘亲属供肾移植的临床疗效进行比较。 结果与结论：同期进行的18例夫妻活体供肾移植组织配型情况较血缘关属供肾移植患者情况差。在移植方案及免疫抑制治疗方案相同的情况下,夫妻活体供肾移植后6个月内血肌酐恢复情况、术后移植肾功能延迟恢、急性排斥反应发生率、感染发生率,均与同期进行的血缘亲属活体供肾移植差异无显著性意义(P > 0.05)。结果表明,无血缘关系的夫妻间供肾移植与血缘亲属供肾移植治疗效果相近。     

撤除糖皮质激素对肾移植受者发生尿微量蛋白的影响

背景：肾移植后长期使用糖皮质激素(以下简称激素)可导致明显的不良反应,少用和不用激素的免疫抑制方案已成为国内外众多肾移植工作者研究的热点。但是,激素减量或撤除存在一定的风险,目前尚未有统一的方案。由于尿微量蛋白在肾小管损伤后可以立刻被检测出来,对肾移植受者而言,监测尿微量蛋白能及早发现移植后肾功能异常,为临床治疗争取时间。 目的：探讨撤除激素(以泼尼松为代表)对肾移植受者发生尿微量蛋白的影响。 方法：35例撤除泼尼松肾移植受者均采用环孢素A或他克莫司+吗替麦考酚酯二联免疫抑制方案,泼尼松开始剂量为30 mg/d,以后逐渐减量(每周减量5 mg),肾移植后1个月停用。其中环孢素A组16例,他克莫司组19例。分别对两组患者肾移植后3,6,12,24个月和加服泼尼松后3,6,12个月进行尿微量蛋白测定与尿蛋白定性测定,同时记录肾移植后2年血肌酐、空腹血糖、体质量增加、急性排斥率、感染、人/肾存活率与加服激素前后24 h尿蛋白定量情况。 结果与结论：两组撤除泼尼松后6个月,尿α1-微球蛋白开始升高;12个月,尿微量白蛋白、尿α1-微球蛋白、尿转铁蛋白明显升高,其中尿蛋白阳性：环孢素A组5例,他克莫司组3例;24个月时,尿微量白蛋白、尿α1-微球蛋白、尿转铁蛋白、尿免疫球蛋白(Ig)G均明显升高,其中尿蛋白阳性：环孢素A组11例,他克莫司组10例,其24 h尿蛋白定量均大于1 g。在此基础上两组加服激素后6个月,尿α1-微球蛋白、尿微量白蛋白开始下降,各1例尿蛋白转阴;12个月,尿微量白蛋白、尿α1-微球蛋白、尿转铁蛋白均下降,尿蛋白转阴：环孢素A组2例,他克莫司组3例,24 h尿蛋白定量在0.7 g左右。肾移植后2年时,环孢素A组血肌酐、急性排斥率高于他克莫司组(P < 0.05),空腹血糖、体质量增加、感染、人/肾存活率两组均无明显差异。结果表明撤除泼尼松对肾移植受者尿微量蛋白的出现影响较大,尤其在肾移植后2年,尿微量白蛋白、尿α1-微球蛋白、尿转铁蛋白、尿免疫球蛋白(Ig)G均明显升高,其安全性有待进一步探讨。 中国组织工程研究杂志出版内容重点：肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程全文链接：     

移植肾血管变异的临床处理

背景：血管吻合技术的好坏直接关系到肾移植的成败。 目的：提高肾移植变异血管吻合的技术方法。 方法：1999年9月至2010年12月广东省第二人民医院器官移植科共完成878例肾移植,对其中供肾存在的动静脉血管变异进行修整、合并、延长等重建处理后进行移植,副肾动脉采用改良支架支撑法同腹壁下动脉吻合。 结果与结论：878例肾移植中,55例供肾动脉变异,肾静脉变异22例,经血管修整重建后均成功与受者髂内或髂外血管吻合。23例直径大于1 mm副肾动脉与腹壁下动脉吻合均取得成功。移植后彩超显示肾动静脉吻合口血流及副肾动脉血流正常。提示移植肾血管变异及副肾动脉只要正确处理,吻合得当,可以安全有效地移植给受者并获良好效果。     

配偶供肾移植后微嵌合体发生与急性排斥反应

背景：微嵌合作为移植物与受者之间的双相细胞移动的标志,在移植免疫耐受中的作用日益受到重视。 目的：探讨夫妻生活与嵌合体的发生,与肾移植后急性排斥反应及其他相关性的研究。 方法：将接受肾脏移植的女性受者(有过生育史的女性除外)分为丈夫活体供肾组、无关男性尸体供肾组,并设立接受妻子活体供肾的对照组。STR方法检测女性受者体内男性供者来源的Y染色体反映微嵌合体的存在,与急性排斥反应发生的关系,并比较配偶间供肾效果的差异。 结果与结论：尽管配偶间供肾移植存在供者年龄偏大以及人类白细胞抗原错配率较高的因素,但与接受无关男性尸肾移植的女性受者相比,接受丈夫活体供肾移植的女性更易检测出微嵌合体,而且肾移植后恢复情况好,急性排斥反应发生率低。而与接受妻子供肾的丈夫相比,接受丈夫供肾的妻子肾移植效果好。说明夫妻间长期相处导致女性接受丈夫体液的机会多,由此产生免疫耐受对于肾移植后人/肾的相容性好,急性排斥反应小。     

活体供肾与尸体供肾:1个器官移植中心2年65:169例肾移植效果比较

背景:活体供肾移植的数量在部分医院已经超过尸体供肾移植,但其安全性、优越性、手术技巧、其所面临的伦理学问题还有待进一步探讨。目的:回顾总结同期完成的活体供肾移植及尸体供肾移植的临床经验,分析不同肾脏来源的肾脏移植术后疗效。方法:收集2006-01/2008-03在解放军第309医院全军器官移植中心接受活体供肾移植的65例受者、接受尸体供肾移植169例受者的临床资料,对不同肾脏来源受者的性别、年龄、HLA位点配型、手术情况、术中和术后近、远期并发症、免疫抑制方案、肾功能恢复情况及长期随访资料进行对照研究,进一步明确活体亲属供肾移植的临床意义。结果与结论:65例活体供肾移植手术均获成功,人/肾1年存活率为100%;尸体供肾移植手术成功,2例因术后3个月出现脑出血等非感染并发症死亡,6例在术后1年内因重症肺部感染呼吸衰竭死亡,人/肾1年存活率95.26%。两种不同来源的肾脏移植在并发症以及人/肾1年存活率等指标上活体供肾移植优于尸体供肾移植。活体供肾移植等待时间短,组织配型好,供肾缺血时间短,排斥反应发生少,移植肾存活率高,是一种安全可行的治疗手段。     

他克莫司和环孢素A对肾移植后患者炎性细胞因子和血脂的影响

背景：环孢素A与他克莫司是肾移植后临床广泛应用的免疫抑制剂。 目的：观察他克莫司和环孢素A对肾移植后炎性细胞因子和血脂的影响。 方法：选择首次接受同种异体肾移植后患者112例,随机分为环孢素A组和他克莫司组,移植后分别给予环孢素A+吗替麦考酚酯+糖皮质激素三联疗法与他克莫司+吗替麦考酚酯+糖皮质激素三联疗法。 结果与结论：他克莫司组的1年人/肾存活率、治疗逆转率高于环孢素A组(P < 0.05),急性排斥反应发生率低于环孢素A组(P < 0.05);移植后1个月及1年的血清白细胞介素2,6,8和血糖水平高于移植前(P < 0.05),低于环孢素A组(P < 0.05),血清白细胞介素4,10低于移植前(P < 0.05),高于环孢素A组(P< 0.05);移植后1个月的血清总胆固醇、三酰甘油和低密度脂蛋白胆固醇高于移植前(P < 0.05),但低于环孢素A组(P < 0.05);移植后1年的血清总胆固醇和低密度脂蛋白胆固醇低于环孢素A组(P < 0.05)。说明他克莫司可通过抑制肾移植后炎性细胞因子释放,改善糖脂代谢等途径降低患者的排斥反应,提高肾移植的存活率。     

亲属活体肾移植供肾多支动脉的重建

背景:近年来亲属活体肾移植在国内开展增多,供肾动脉血管变异较为常见,因此需重视动脉重建的方法,以保证手术的合理性和安全性。在临床实践中发现供肾多支动脉的情况较为常见,而亲属活体肾移植国内刚刚起步,相关经验尚少。目的:总结亲属活体供肾多支动脉的血管重建方式在肾移植中的应用经验。方法:2006-01/2008-12完成38例亲属活体肾移植,其中供肾单支动脉30例,多支动脉8例。术中证实多支动脉供肾中5例供者2支动脉变异,2例供者3支动脉变异,1例供者4支动脉变异。多支动脉供肾分别采用侧侧共干吻合或端侧吻合后分别与髂内动脉或髂外动脉吻合。观察肾移植手术结果及近期随访结果。结果与结论:8例多支动脉供肾者肾移植后7～10d出院,均未输血,未出现并发症。受者肾移植后随访6～36个月,平均13个月,未见急性肾小管坏死、肾血管栓塞、肾动脉狭窄、假性动脉瘤等并发症,彩色多普勒超声检查示移植肾血供均良好。多支动脉供肾组受者吻合血管开放后泌尿时间、血肌酐水平与单支动脉供肾组差异均无显著性意义(P0.05)。提示选择合适方法进行血管重建,不会影响肾移植效果,采用受者的髂内动脉及其分支进行血管重建安全可行。     

活体肝移植和尸体肝移植过程中患者肾功能的比较

背景：原位肝移植中诸多因素可导致移植后急性肾功能衰竭,但不同移植方式对移植过程中患者肾功能的影响并不清楚。 目的：比较活体部分供肝移植和尸体全肝移植对移植过程中患者肾功能的影响。 方法：纳入拟行活体部分供肝原位肝移植的晚期肝病患者15例设为活体组,采用背驮式原位肝移植;另与同期进行的尸体全肝移植20例患者设为尸体组,采用非转流经典原位肝移植。分别于切皮前即刻、切皮后1 h、无肝期30 min、新肝期1 h及新肝期4 h测定血流动力学和肾功能指标。 结果与结论：两组患者各时间点平均动脉压、心率比较差异无显著性意义(P > 0.05),活体组无肝期30 min时心输出量、心指数高于尸体组,而体循环血管阻力、体循环血管阻力指数低于尸体组(P < 0.05)。两组移植过程中各时点血清胱抑素C、β2-微球蛋白、肌酐及肌酐清除率均在正常范围内,总尿量及呋噻米用量比较差异无显著性意义(P > 0.05),但活体组无肝期分钟尿量明显多于尸体组(P  < 0.05)。提示活体部分供肝移植和尸体全肝移植对移植过程中患者肾功能均未产生不利影响。     

A pilot study of calcineurin inhibitors (CNIs) and steroid avoidance immunosuppressive protocol among living donor kidney transplant recipients

Calcineurin Inhibitors (CNIs) and Corticosteroids have been the main immunosuppressive agents in solid organ transplantation. Many studies have confirmed the positive impacts of withdrawal/avoidance of these agents, separately, on their side effect profiles. A pilot study was performed avoiding both agents among low-immunological-risk living donor kidney transplant recipients at a single center. Seventeen recipients were maintained on the double avoidance protocol during the study period beginning July 2002 through December 2003. Three rejection episodes occurred (out of ten) among related donor kidney recipients and six episodes (out of seven) among unrelated donor kidney recipients. Although most of the rejections were reversed with a short course of corticosteroids, the protocol was revised to exclude the unrelated donor kidney recipients. There were higher incidences of wound complications among recipients who received the initial loading dose of Sirolimus. Double avoidance of CNIs and corticosteroids is possible in living donor kidney transplant recipients with an acceptable incidence of rejection. Proper management of the side effects of Sirolimus could further minimize the incidence of rejection. A multi-center randomized study is recommended in order to recognize the benefits of avoiding CNIs and corticosteroids in renal transplant recipients.     

Improved graft survival after renal transplantation in the United States, 1988 to 1996

BACKGROUND: The introduction of cyclosporine has resulted in improvement in the short-term outcome of renal transplantation, but its effect on the long-term survival of kidney transplants is not known. METHODS: We analyzed the influence of demographic characteristics (age, sex, and race), transplant-related variables (living or cadaveric donor, panel-reactive antibody titer, extent of HLA matching, and cold-ischemia time), and post-transplantation variables (presence or absence of acute rejection, delayed graft function, and therapy with mycophenolate mofetil and tacrolimus) on graft survival for all 93,934 renal transplantations performed in the United States between 1988 and 1996. A regression analysis adjusted for these variables was used to estimate the risk of graft failure within the first year and more than one year after transplantation. RESULTS: From 1988 to 1996, the one-year survival rate for grafts from living donors increased from 88.8 to 93.9 percent, and the rate for cadaveric grafts increased from 75.7 to 87.7 percent. The half-life for grafts from living donors increased steadily from 12.7 to 21.6 years, and that for cadaveric grafts increased from 7.9 to 13.8 years. After censoring of data for patients who died with functioning grafts, the half-life for grafts from living donors increased from 16.9 years to 35.9 years, and that for cadaveric grafts increased from 11.0 years to 19.5 years. The average yearly reduction in the relative hazard of graft failure after one year was 4.2 percent for all recipients (P<0.001), 0.4 percent for those who had acute rejection (P=0.57), and 6.3 percent for those who did not have acute rejection (P<0.001). CONCLUSIONS: Since 1988, there has been a substantial increase in short-term and long-term survival of kidney grafts from both living and cadaveric donors.     

DNA damage in kidney transplant patients. Role of organ origin

Chronic kidney disease (CKD) patients are characterized by elevated levels of genomic damage. This damage increases when kidney function decreases being maximum in hemodialysis patients. As kidney transplantation improves renal function, and it is related with better survival, the aim of our study was to evaluate potential changes in DNA damage levels after kidney transplantation, and comparing living donor recipients with cadaveric donor recipients. The alkaline comet assay was used to determine DNA breaks and oxidative damaged DNA; and the micronucleus assay was used to determine chromosomal breakage and/or aneuploidy. Fifty CKD patients were followed up after 6 and 12 months of their kidney transplantation. All patients increased their genomic damage levels after 6 and 12 months of renal transplantation, compared with those observed before transplantation, despite of the improvement of their metabolic functions. Donor advanced age correlated positively with higher DNA damage. Genomic damage was lower in living donor transplants with respect to cadaveric donor transplants. Our conclusion is that DNA damage increased in kidney transplantation patients, whereas their renal function improved. Higher levels of DNA damage were found in cadaveric donor transplants when compared to living donor transplants. Environ. Mol. Mutagen. 58:712–718, 2017. © 2017 Wiley Periodicals, Inc.     

Establishment of simultaneous pancreas and kidney transplantation (SPK) model with cuff technique and portal venous drainage in rats

Objective: To establish a simultaneous pancreas and kidney transplantation (SPK) model in the rat. Methods: SD rats served as donors and recipients. The donor portal vein and the recipient superior mesenteric vein were anastomosed and the donor renal veins and recipient renal veins were anastomosed by cuff method. Arterial reconstruction was carried out by end to side anastomosis of the donor abdominal aorta to the recipient abdominal aorta. Enteric drainage was performed by side to side anastomosis between donors' duodenum and recipients' jejunum. The donor ureter -bladder valve was anastomosed to the bladder of recipients.Results: Out of 30 cases of SPK transplantation, 24 had normal serum glucose and serum creatinine after operation. The successful rate was 80 %. Conclusion: This model of SPK in rats is stable and reliable, which could be applied for further scientific research.     

The influence of mycophenolate mofetil and azathioprine on the same cadaveric donor renal transplantation

In order to evaluate whether immunosuppressive agents such as mycophenolate mofetil (MMF) and azathioprine would differently influence the outcome of the renal transplants, we prospectively analyzed the incidence of acute rejection episodes, cytomegalovirus infection within the first 6 months following renal transplantation and 5 yr graft survival rate after minimizing influences of donor factors by grafting the same cadaveric donor kidney. There was no significant difference in sex, HLA mismatch, cold ischemic time, and patients' weight between the two groups. Contrary to the previous studies which demonstrated that MMF could lower the incidence of acute rejection episodes and improved graft survival rate, the two groups showed no significant difference in the incidence of acute rejection episodes and 5-yr graft survival rate as well. This discrepancy in these results might explain that donor factors could be important to cadaveric renal transplantation. Thus, we suggest that the influences of donor factors should be considered in further clinical studies of cadaveric renal transplantation.