再次肾移植受者和移植肾长期预后影响因素分析

目的探究再次肾移植受者和移植肾存活情况及长期预后影响因素。 方法回顾性分析1991年1月1日至2017年12月31日于浙江大学医学院附属第一医院肾脏病中心接受肾移植受者临床资料。共纳入再次肾移植受者37例,首次肾移植受者5 374例。根据再次肾移植受者移植肾存活时间长短,将其分为长期存活组(19例,>5年)和短期存活组(18例,≤5年)。采用成组t检验比较长期和短期存活组供受者年龄、首次与再次肾移植间隔时间、HLA错配数和再次移植供肾冷/热缺血时间。采用卡方检验比较长期和短期存活组受者性别、再次移植供肾类型、再次移植前后群体反应性抗体阳性比例、首次移植失功移植肾切除比例、再次移植前免疫诱导比例及再次移植后移植肾功能延迟恢复(DGF)和急性排斥反应发生比例。采用Kaplan-Meier法分析再次和首次肾移植受者/移植肾1、5和10年存活率。采用Cox比例风险模型分析影响再次肾移植术后移植肾长期存活影响因素。P<0.05为差异有统计学意义。 结果截至2018年3月1日,37例再次肾移植受者中位随访时间为152个月(11～323个月),2例死亡,18例发生移植肾失功,17例移植肾功能稳定。5 374例首次肾移植受者中位随访时间为108.9个月(0.1～350.0个月),459例死亡,1 343例发生移植肾失功。再次移植组受者/移植肾1、5和10年存活率分别为86%/81%、86%/62%和82%/36%,首次移植组受者/移植肾1、5和10年存活率分别为99%/98%、93%/89%和88%/80%。再次移植组移植肾1、5和10年存活率均低于首次移植组(χ²＝60.816、25.110和43.900,P均<0.05);再次移植组受者1年存活率低于首次移植组,差异有统计学意义(χ²＝40.409,P<0.05)。长期和短期存活组受者再次移植后移植肾DGF和急性排斥反应发生比例差异均有统计学意义(χ²＝4.039和4.748,P均<0.05)。Cox回归分析结果示DGF和急性排斥反应是影响再次肾移植受者移植肾长期存活的独立危险因素,差异有统计学意义(RR＝4.317和4.571,P均<0.05)。 结论再次肾移植受者移植肾存活率低于首次肾移植受者,DGF和急性排斥反应是影响再次移植受者移植肾存活的独立危险因素。     

心脏死亡器官捐献供肾移植单中心60例经验总结

目的 探讨单中心DCD供肾移植的临床效果,总结DCD供肾移植的经验.方法 回顾性分析2011年12月至2013年4月间60例DCD和112例DCD供肾移植的临床资料.结果 依据《中国心脏死亡器官捐献指南》,实施DCD 60例,共捐献肾脏118个,实施肾移植112例.14例受者术后发生移植肾功能延迟恢复(DGF),发生率12.5％,其中未使用LifePort机械灌注冷保存DGF发生率23.1％ (6/26),使用LifePort移植肾DGF发生率9.3％(8/86).14例DGF受者4例切除移植肾,10例肾功能术后16～52 d恢复正常.急性排斥反应发生率6.3％(7/112),其中1例术后第12天移植肾破裂切除肾脏,其余经治疗后逆转.1例受者术后第15天因急性心肌梗死亡,1例术后第7天发生急性心功能衰竭死亡.移植肾存活的105例受者,随访1～15个月,移植肾功能正常.结论 在我国实施DCD切实可行,是符合伦理和我国国情的器官来源根本途径.DCD供肾移植临床效果良好,Lifeport具有清除肾脏残余微血栓、疏通肾脏微血管、评估肾脏功能及预防DGF的良好作用.     

致敏患者经双滤过法血浆分离方案预处理后行肾移植的临床效果分析

目的 分析致敏患者经双滤过法血浆分离(DFPP)方案预处理,并联合使用抗CD25单抗诱导治疗后行肾移植的临床效果和安全性.方法 回顾性分析2000年11至2012年1月45例致敏受者在肾移植前经DFPP方案预处理,并联合使用抗CD25单抗诱导治疗后接受肾移植的临床资料.所有受者预处理前的群体反应性抗体(PRA)水平均大于20％,为(56.5±19.9)％,预处理后PRA水平降至(18.9±19.1)％.受者与供者的HLA抗原错配数为(2.1±0.7)个,术前2次供、受者淋巴细胞毒交叉配型试验均为阴性.所有受者术后至少随访1年,观察术后1年受者和移植肾存活率,以及排斥反应和肺部感染的发生情况.结果 随访期间,无受者死亡,有2例受者发生移植肾功能丧失,术后1年受者存活率为100％(45/45),移植肾存活率为95.6％ (43/45).术中肾血管开放后1例发生超急性排斥反应,发生率为2.2％,受者在切除移植肾后恢复血液透析;术后发生急性排斥反应12例,发生率为26.7％(12/45),经甲泼尼龙和(或)ATG冲击治疗后,11例完全逆转,1例出现移植肾功能丧失而恢复血液透析.术后肺部感染发生率为8.9％(4/45),经抗感染治疗后均好转,未发生重症肺部感染.结论 肾移植前采用DFPP 预处理,并联合使用抗CD25单抗诱导治疗安全有效,能使致敏受者获得良好的肾移植效果.     

乙型肝炎免疫球蛋白预防肾移植后新发乙型肝炎

目的 探讨肾移植受者应用小剂量乙型肝炎免疫球蛋白(HBIG)预防术后新发乙型肝炎的安全性和有效性.方法 回顾性分析单中心2007年1月至2010年6月间肾移植受者的资料,将术前无乙型肝炎的138例受者作为试验组,术前肌肉注射小剂量HBIG,术后定期监测乙型肝炎表面抗体(HBsAb)滴度,根据其滴度调整术后应用HBIG的剂量,持续应用1年或1年以上.将2004年1月至2006年12月间术前无乙型肝炎的196例肾移植受者作为对照组,不采用乙型肝炎预防措施.观察两组移植后新发乙型肝炎的发病率,并记录急性排斥反应发生情况、受者和移植肾1年存活率.结果 随访12个月,试验组仅1例(0.7％)于术后6个月出现新发乙型肝炎,对照组11例(5.6％)出现新发乙型肝炎,其中2例因爆发性肝功能衰竭而死亡.两组新发乙型肝炎发病率的差异有统计学意义(P＜0.05).术后6个月内,试验组有19例(13.8％)发生急性排斥反应,对照组有34例(17.3％)发生急性排斥反应,两组急性排斥反应发生率的差异无统计学意义(P＞0.05).试验组受者1年存活率为97.8％(135/138),移植肾1年存活率为(96.4％,133/138);对照组受者1年存活率为(91.8％,180/196),移植肾1年存活率为(90.3％,177/196).两组受者和移植肾1年存活率的差异有统计学意义(P＜0.05.P＜0.05).结论 小剂量HBIG用于肾移植后预防新发乙型肝炎是安全、有效的.     

心脏死亡器官捐献供肾移植与司法途径标准供者供肾移植术后早期效果分析比较

目的比较心脏死亡器官捐献(DCD)和司法途径标准供者(SCD)供肾移植的早期效果。方法回顾性分析2011年1月至2014年12月在武汉大学人民医院施行的DCD供肾移植74例(DCD组)以及同期施行的SCD供肾移植143例(SCD组)。所有患者均采用抗体诱导和三联免疫抑制方案(吗替麦考酚酯+他克莫司+泼尼松)。随访评价两组受者短期移植肾功能、移植肾和受者短期存活情况,并追踪移植物功能延迟恢复(DGF)、急性排斥反应、肺部感染发生率。采用成组t检验比较两组受者年龄、热缺血时间、冷缺血时间等指标。两组移植肾受者存活情况、DGF发生率、急性排斥反应发生率、肺部感染发生率使用卡方检验进行比较。P0.05为差异有统计学意义。结果截至2015年8月,DCD组随访时间平均(23±13)个月,SCD组随访时间平均(25±17)个月。肾移植术后6个月,DCD组和SCD组受者存活比例分别为93.2%(69/74)和94.4%(135/143),移植肾存活比例分别为90.5%(67/74)和93.0%(133/143),差异均无统计学意义(χ2=0.12和0.41,P均0.05)。DCD组和SCD组DGF发生率分别为28.4%(21/74)和7.0%(10/143),差异有统计学意义(χ2=18.21,P0.05)。术后6个月内DCD组和SCD组急性排斥反应发生率分别13.5%(10/74)和7.0%(10/143),肺部感染发生率分别为14.9%(11/74)和21.0%(30/143),差异均无统计学意义(χ2=2.48和1.19,P均0.05)。术后1、3个月DCD组血清肌酐分别为(149±65)、(132±78)μmol/L,均高于SCD组(t=4.74和2.95,P均0.05),术后6个月两组血清肌酐差异无统计学意义(t=1.22,P0.05)。结论与SCD供肾移植相比,DCD供肾移植术后DGF发生率较高,急性排斥反应增加,短期内移植肾功能较差,其远期存活效果仍需要继续随访观察。     

急性体液性排斥反应对移植肾预后的影响

目的 探讨急性体液性排斥反应对移植肾预后的影响.方法 共有1098例接受首次尸体肾移植的受者纳入研究.所有受者术后均采用以他克莫司或环孢素A为基础的三联免疫抑制方案,当发生排斥反应时,采用甲泼尼龙冲击治疗,疗效较差者则联合应用莫罗单抗-CD3或丙种球蛋白或行血浆置换进行治疗.术后1年内经病理检查证实,有53例受者发生急性体液性排斥反应(急性体液性排斥反应组),109例发生急性细胞性排斥反应(急性细胞性排斥反应组),其余936例受者术后1年内肾功能稳定(对照组).分析和比较3组受者性别、年龄、术前淋巴毒、HLA抗原错配数、群体反应性抗体(PRA)水平及供肾冷/热缺血时间等冈素间的差异,比较3组受者术后移植肾功能丧失情况及移植肾存活率,分析完全逆转的急性体液性排斥反应与细胞性排斥反应对移植肾预后的影响.结果 3组受者在性别、年龄、术前淋巴细胞毒性试验、供肾冷缺血时间及术后随访时间等方面比较,差异均无统计学意义(P＜0.05).急性体液性排斥反应组和急性细胞性排斥反应组受者在术前HLA抗原错配数、PRA水平及供肾热缺血时间等方面均明显高于对照组,与对照组比较,差异均有统计学意义(P＜0.05).随访期间,急性体液性排斥反应组受者移植肾功能丧失的发生率为27.4%(14/53),明显高于急性细胞性排斥反应组的7.3%(8/109)和对照组的2.2%(21/936),3组间差异均有统计学意义(P＜0.01).通过kaplan-meier生存分析发现,急性体液性排斥反应组受者的移植肾存活率明显低于急性细胞性排斥反应组和对照组(P＜0.01).剔除发生排斥反应后未逆转者,3组间移植肾存活率的比较,差异均无统计学意义(P＞0.05).结论 急性体液性排斥反应明显影响移植肾存活,但完全逆转的急性体液排斥反应并不影响移植肾的预后.     

活体肾移植前对致敏患者的处理经验及疗效分析

目的 总结活体肾移植前对致敏患者的处理经验,并对移植效果进行分析.方法 回顾性分析609例活体肾移植受者的临床资料.根据移植前群体反应性抗体(PRA)水平将受者分为高致敏组(41例,PRA≥30％),低致敏组(102例,PRA为0～30％)和非致敏组(466例,PRA为0).所有受者经HLA抗体检测和淋巴细胞毒交叉配合试验(CDC)确认没有针对供者的HLA抗体后进行肾移植.高致敏组给予抗胸腺细胞球蛋白诱导治疗,低致敏组给予抗白细胞介素2受体单抗诱导治疗.随访1年以上,观察各组术后移植肾功能、急性排斥反应发生率、受者和移植肾存活率及并发症发生率.结果 高致敏组、低致敏组和非致敏组受者术后移植肾恢复正常的时间和1年时肾小球滤过率均无明显差异;3组均未发生超急性排斥反应,急性排斥反应发生率分别为9.76％(4/41)、8.82％(9/102)和8.15％(38/466),术后1年移植肾存活率分别为97.6％(40/41)、97.1％(99/102)和98.1％(457/466),受者存活率分别为97.6％(40/41)、98.0％(100/102)和98.9％(461/466),3组间上述指标的差异均无统计学意义(P＞0.05).高致敏组的感染发生率为31.7％(13/41),明显高于低致敏组的26.5％(27/102)和非致敏组的21.6％ (101/466) (P＜0.05).结论 致敏受者肾移植前经HLA抗体检测和CDC配型,避开受者体内供者特异性抗体针对的供肾,并给予免疫诱导治疗,可以获得与非致敏受者相似的良好效果.     

公民逝世后器官捐献供肾移植临床分析

目的探讨公民逝世后器官捐献供肾移植的近期临床效果。方法公民逝世后器官捐献供肾移植73例,供者43例,其中本院器官获取组织42例,外院器官获取组织分享1例。分析肾移植术后人/肾存活率和并发症的发生情况。结果 73例受者随访9~38个月,术后6个月、1年的人/肾存活率分别为97.3%/94.5%、94.5%/91.8%。10例(13.7%)受者发生移植肾功能恢复延迟,15例(20.5%)受者术后发生急性排斥反应,21例(28.8%)受者发生肺部感染。2例受者移植肾丢失,4例受者移植肾带功死亡。结论公民逝世后器官捐献供肾移植近期疗效较好,是解决供肾来源的有效途径。     

儿童肾移植术后排斥反应的临床分析

目的探讨儿童肾移植受者排斥反应的发病特点与治疗预后。方法回顾性分析中山大学附属第一医院器官移植中心2013年1月至2022年6月间实施的360例次儿童肾移植受者的临床资料, 分析儿童受者排斥反应发病特点及治疗预后。采用非参数秩和检验比较不同分组间血肌酐值, Kaplan-Meier法和Log-rank法分析排斥反应发生率和不同排斥次数的死亡删失移植肾存活率。结果共有58例受者发生82次排斥反应, 术后3个月、6个月和1年的累积排斥反应发生率分别为6.3%、9.2%和11.3%。病理活检证实的排斥反应有50次, 其中细胞性排斥反应(T cell mediated rejection, TCMR)占42.0%(21/50), 抗体介导的排斥反应(antibody mediated rejection, ABMR)占20.0%(10/50), 混合性排斥反应占38.0%(19/50)。58例受者首次排斥反应治疗后, 69.0%(40/58)的移植肾功能稳定, 31.0%(18/58)的移植肾功能受损;发生临床排斥、ABMR和交界性排斥受者中分别有80.8%(21/26)、85.7%(6/7)...     

器官移植术后的嵌合现象

为研究器官移植术后的嵌合现象，术后利用聚合酶链反应（ＰＣＲ）技术检测３例接受男性供体器官的女性受者外周血及皮肤组织中的Ｙ染色体特异性ＤＮＡ片段。结果在１例小肠移植受者的外周血及皮肤组织中出现Ｙ染色体特异性ＤＮＡ片段；２例肾移植受者的外周血中也出现Ｙ染色体特异性ＤＮＡ片段。表明在器官移植术后存在着供体细胞向受体组织的移行嵌合。认为促进嵌合的出现及保持嵌合的平衡，将有利于防治排斥反应和移植物抗宿主病。     

Prospective study of microchimerism in renal allograft recipients: association between HLA-DR matching, microchimerism and acute rejection

The presence of donor-derived hematopoietic cells in blood and various tissues of the organ recipients, termed allogeneic microchimerism, has been considered to play an essential role in establishment of organ acceptance. In this study, we prospectively determined the presence of peripheral blood microchimerism (PBM) in 20 male-to-female renal allograft recipients up to 30 months post-transplantation. Recipients were categorized according to the pattern of microchimerism into microchimeric and nonmicrochimeric groups, and then state of human leukocyte antigens (HLA) Class II (DR/DQ) matching, episodes of acute rejection, age at transplantation, renal function, and history of blood transfusion were compared. DNA was extracted from donor, pre-transplant, and post-transplant (1 wk; 1, 3, 6, 12, 18, 24, and 30 months) peripheral blood samples. We analyzed PBM using nested polymerase chain reaction (PCR) amplification specific for the SRY region of the Y chromosome with a sensitivity up to 1:1 000 000. Microchimerism was detected in 13 (65%) of 20 recipients at various intervals. The highest frequency of microchimerism was at 1 wk (55%). Among microchimeric recipients, none were positive on all post-transplant analyses. Interestingly, nonmicrochimeric cases were negative throughout the study. The three recipients with an episode of acute rejection during the first week after transplantation were all in the nonmicrochimeric group with completely mismatched HLA-DR antigens. HLA-DR incompatibility was significantly lower (t-test, p<0.05) in microchimeric cases (1.0+/-0.58) than in nonmicrochimeric ones (1.9+/-0.38). But regarding HLA-DQ and other clinical parameters mentioned above, significant difference was not observed. We propose that there is an association between HLA-DR matching, microchimerism and acute graft rejection in our recipients. Our study demonstrates that, with routine immunosuppressive protocols, higher compatibility of HLA-DR antigens facilitates microchimerism induction. Then, development of new stronger immunosuppressive protocols (including conditioning) or augmentation of chimeric state (by donor-specific bone marrow infusion), especially in completely mismatched HLA-DR renal allograft recipients, may be useful for graft acceptance.     

Microchimerism and renal transplantation: doubt still persists

OBJECTIVE: We sought to study microchimerism in a group of kidney transplant recipients. MATERIALS AND METHODS: In this study, the peripheral blood microchimerism (PBM) after renal transplantation was retrospectively evaluated in 32 male-to-female recipients of living unrelated or cadaveric donor renal transplants. Using a nested polymerase chain reaction (PCR) amplification specific for SRY region of the Y chromosome, microchimerism was detected with a sensitivity of 1:1,000,000. Recipients were compared according to the presence of PBM, acute and chronic rejection episodes, type of allotransplant, recipient and donor age at transplantation, previous male labor or blood transfusion, allograft function (serum creatinine level), and body mass index. RESULTS: Among 32 recipients, 7 (21.9%) were positive for PBM upon multiple testing at various posttransplant times. All microchimeric recipients had received kidneys from living unrelated donors. No significant difference was observed with regard to other parameters. In addition the acute rejection rate in the microchimeric group was 3 (42%) versus 4 (16%) in the nonmicrochimeric recipients (not significant). CONCLUSION: Our results suggested better establishment of microchimerism after living donor kidney transplantation. However, doubt persists concerning the true effect of microchimerism after renal transplantation. It seems that microchimerism alone has no major protective role upon renal allograft survival.     

Early Microchimerism in Peripheral Blood Following Kidney Transplantation

Background

The role of microchimerism found in the peripheral blood of renal transplant recipients remains a matter of debate. We assessed the frequency of microchimerism after kidney transplantation and examined its influence on clinical courses over a 12-month follow-up period.

Patients and Methods

Ten single-kidney recipients underwent microchimerism detection at 2 days, 2 weeks, and 1, 3, 6, and 12 months after transplantation, with mismatch human leukocyte antigen (HLA)-A, -B, and -C used as markers.

Results

Microchimerism was detected in 8 (80%) patients at 2 days after kidney transplantation. In 3 of those, microchimerism became negative within 3 months after transplantation, whereas it remained present for up to 12 months in 3 patients (33 %). There was 1 acute rejection episode in a patient in whom microchimerism became negative within 3 months. Protocol renal graft biopsy specimens obtained 3 months after transplantation revealed no acute cellular-mediated rejection (ACMR) or acute antibody-mediated rejection (AAMR) in the 5 patients positive for microchimerism at 3 months.

Conclusions

Microchimerism was frequently detected after kidney transplantation. Microchimerism that remained for more than 3 months post-transplantation might be correlated with a lower incidence of rejection, thus its monitoring may help identify recipients with a low rejection risk.     

Indefinite survival of rat islet allografts following infusion of donor bone marrow without cytoablation

We have tested the effect of donor bone marrow cell (DBMC) infusion on the survival of pancreatic islet allografts in the rat, without the use of cytoablative recipient conditioning. Lewis and diabetic Brown Norway rats were used as donors and recipients, respectively. Donor islets were placed beneath the left renal capsule. Infusion of DBMC and temporary immunosuppression followed by delayed islet transplantation resulted in indefinite survival of all islet grafts (MST >180 days). Control animals demonstrated recurrent hyperglycemia (islet allografts rejection). Donor bone marrow derived cells were detected in the spleen and cervical lymph nodes of BN recipients of LEW bone marrow but not in the recipients of islet transplants alone. Second set full thickness skin grafts were performed in normal BN and in recipients of a previously successful ITX. Donor specific skin grafts were accepted in the animals that had received DBMC 40 days before the islet allograft, while animals receiving DBMC at the time of the islet allograft rejected the donor specific skin graft similarly to the controls. However, these animals did not reject a second set donor-specific islet transplant. The results indicate that radiation conditioning of the recipients was not necessary to induce microchimerism and graft acceptance in this rodent model of islet allotransplantation.     

Microchimerism in Peripheral Blood and Urine in Renal Transplant Recipients: Preliminary Results

The role of microchimerism in peripheral blood and urine of renal transplant recipients remains a matter of debate, depending on the sensitivity of the methods used for detection. We studied 17 female renal transplant recipients who had received renal allografts from male donors. Polymerase chain reaction (PCR) was applied to blood and urine for the microsatellite markers D1S80, DYZ1, TH01, and kαi SE33. Detection of DYZ1 that is present only on the Y chromosome was considered proof for microchimerism. No microchimerism was detected in peripheral blood, whereas it could be detected in the urine of 8/17 (48%) patients. There were no differences between patients with and without microchimerism regarding patient age, dialysis vintage, immunosuppression, time post-transplantation, and allograft function as measured using serum creatinine, creatinine clearance, and proteinuria. Two patients in each group showed chronic allograft dysfunction. These findings raise questions regarding the role of microchimerism in renal transplantation.     

Novel surveillance and cure of a donor-transmitted lymphoma in a renal allograft recipient

BACKGROUND: In this report we describe a malignant lymphoma of donor origin inadvertently transplanted into two renal allograft recipients, despite standard comprehensive donor screening. The successful clearance of the tumor from both patients and a novel method of surveillance are detailed. METHODS: Initial management consisted of withdrawal of immunosuppression to promote rejection of the allograft and the transplanted tumor in both patients, followed by graft removal. Peripheral blood microchimerism was assessed in both recipients using nested polymerase chain reaction to detect the DYZ3 gene on the Y chromosome (donor male, recipients female). RESULTS: Although microchimerism was detected on day 6 after transplantation and day 1 after explantation, repeat peripheral blood examination at 1, 3, and 6 months after explantation demonstrated no microchimerism. Both patients remain well at 12 months and have been relisted for transplantation. CONCLUSION: Despite inadvertent transplantation of a previously undiagnosed malignancy of donor origin, the recipients' immune response was able to eliminate donor tumor cells after the withdrawal of immunosuppression. Repeated surveillance of peripheral blood from both recipients, using a novel application of the technique of nested polymerase chain reaction to amplify donor DNA, demonstrated no persistence of donor cells, supporting effective eradication of the donor malignancy.     

Development of donor-specific microchimerism in liver transplant recipient with HLA-DRB1 and -DQB1 mismatch related to rejection episodes

Migration of donor-derived cells to recipient tissues after liver transplantation has been suggested as a mechanism to induce and maintain allograft tolerance, although important issues remain including acute rejection posttransplantation mortality, and complications related to immunosuppressive therapy. We therefore examined the relation of rejection to chimerism based upon recipient and donor mismatch of HLA-DRB1 and -DQB1 alleles. Laboratory analysis of peripheral blood was performed before and 10 days to 16 months after liver transplantation in 32 recipients, using ganglion or spleen cell samples of respective donors. DNA was extracted for HLA-DRB1 and DQB1 allele typing using polymerase chain reactions with sequence-specific primers (PCR-SSP). Microchimerism was analyzed through nested PCR. Our results confirmed that patients with one or two mismatched HLA-DRB1 and-DQB1 alleles showed microchimerism and no rejection (P <.05). Microchimerism was present in 71.88% of the patients, and a significant association of rejection P <.05 was found when microchimerism was correlated to graft rejection. These results suggest that the presence of microchimerism may be associated with acceptance, tolerance and survival of the allograft.     

肾移植后供者细胞的迁移和嵌合

采用聚合酶链反应（ＰＣＲ）技术对１９８７年７月～１９９６年６月接受男性供肾的５７例女性受者的嵌合状态进行研究。发现嵌合总发生率为５４．４％（３１／５７）；生存期３年以上的受者嵌合发生率为６６．７％（１８／２７），而三年以内嵌合发生率为４３．３％（１３／３０），两者差异有显著性（Ｐ＜０．０５）；肾移植后２个月内，嵌合的形成尚不稳定。结果表明：随着肾移植受者生存期的延长，嵌合的发生率相应增高；嵌合反映了供者器官与受者免疫系统之间双向作用的关系，并与免疫耐受存在某种联系。     

Detection of chimerism following vascularized bone allotransplantation by polymerase chain reaction using a Y-chromosome specific primer.

Chimerism following allogeneic organ transplantation is a phenomenon known to occur and be associated with development of immunologic tolerance in allotransplantation. However, little is known about graft cell migration following vascularized bone allografting. In this study, chimerism was assessed following vascularized tibia transplantation from male DA or PVG donors to female PVG rat recipients using a semi-quantitative polymerase chain reaction for the Y-chromosome. FK-506 (Tacrolimus) was administered after transplantation for immunosuppression. All immunosuppresssed PVG rat recipients of PVG bone grafts showed a high level of chimerism (1%) in the thymus, spleen, liver and cervical lymph nodes at 18 weeks post-transplant. Donor cells were also detected in the contralateral tibia and humerus. In non-immunosuppressed PVG rat recipients of DA bone grafts, donor cells were detected in the spleen in three of five rats within 2 weeks post-transplant. In these animals the bone grafts were severely rejected. In immunosuppressed PVG rat recipients of DA bone grafts, two of five, four of eight and eight of 10 rats showed low level chimerism (0.1%) in peripheral blood at 1, 12, and 18 weeks post-transplant. Six rats showed a high level of chimerism in the spleen and thymus. Histological studies revealed no rejection findings through 18 weeks post-transplant. Our results indicate that chimerism, or the presence of graft cells in host tissue, may occur in the face of acute rejection and be demonstrable following vascularized isograft and allograft living bone transplantation when chronic immunosuppression is maintained. Graft vascular patency during the short-term likely allows cellular migration, even in the face of acute rejection. Long-term survival and proliferation of graft marrow elements in host tissue may be possible with adequate immunosuppression.     

Stability of renal allograft function associated with long-term cyclosporine immunosuppressive therapy--five year follow-up

To examine the evolution of renal allograft function in kidney transplant recipients receiving long-term cyclosporine therapy, we evaluated 50 cadaveric and 30 living-related renal transplant recipients having graft survival greater than or equal to 12 months and an opportunity for 5 years of follow-up. Linear analysis of long-term allograft function in each patient was undertaken by plotting reciprocal serum creatinine (1/Crs) values vs. time. Mean follow-up was 49 +/- 18 months. Actual 3-year and 5-year allograft survivals were 83.8% (n = 80) [corrected] and 73.3% (n = 75) [corrected], respectively. Collective analyses of values of 1/Crs measured at yearly intervals and of the slopes of the curves obtained by plotting 1/Crs vs. time for each patient suggested that long-term use of CsA is associated with impaired but generally stable allograft function 1-5 years posttransplant. The aggregate rate of decline of renal allograft function in the study population did not differ from that of a historical control group consisting of 59 renal transplant recipients treated with a conventional prednisone-azathioprine immunosuppressive regimen. Donor source, diabetes, and diastolic hypertension (diastolic BP greater than 95 mmHg in more than half the follow-up readings) were not correlated with a more rapid rate of decline of allograft function as reflected in the slopes of the 1/Crs vs. time curves between 12 months posttransplant and the end of follow-up. In contrast, a significantly greater rate of decline of cadaveric allograft function was observed in patients with 12-month Crs values greater than 2.5 mg% and recipients of greater than 2 HLA-A,B-mismatched cadaveric kidneys. The data do not support an indication for routine conversion from CsA to azathioprine following successful renal transplantation.