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1.
目的 探讨服用环孢素A(CsA)的肾移植受者药代动力学特性与术后早期移植肾急性排斥及CsA肾中毒的关系。方法  4 7例肾移植受者术后服用CsA 6mg·kg-1·d-1,7d后留取服药即刻及服药后 1、2、3、4、5、6、8、10及 12h的血样 ,测定全血CsA浓度 ,计算各自的药代动力学参数。根据检测后 1个月内移植肾功能状况进行分组 ,回顾分析各组受者药代动力学指标的差异。结果  4 7例肾移植受者中 ,观察期内共有 12例出现急性排斥反应 ,7例出现CsA肾中毒 ,其余 2 8例移植肾功能稳定。急性排斥组CsA吸收半衰期 (T1/2 (a) )、清除半衰期 (T1/2 (e) )、药物清除率 (CL/F)、达峰值时间 (Tmax)及浓度 时间曲线下面积 (AUC)与肾功能稳定组比较 ,差异有显著性 ;CsA肾中毒组的T1/2 (e) 、CL/F、Tmax及AUC与稳定组比较 ,差异均有显著性。结论 通过多点浓度进行CsA的药代动力学检测可以较准确反映肾移植受者的药物暴露剂量强度 ;CsA吸收清除较快的患者 ,容易出现急性排斥 ,而清除慢的患者存在并发CsA肾中毒的危险。  相似文献   

2.
目的:探讨供受者HLA致敏原性错配(IM)对肾移植受者急性排斥反应发生率的影响。方法:回顾性分析196例首次肾移植受者IM对肾移植术后肾功能的恢复时间及1年内排斥反应发生率情况。结果:IM对肾移植术后肾功能恢复时间无明显影响;IM患者1年内急性排斥率明显增加;各类位点IM对肾移植术后急性排斥反应的影响进行比较,A位点影响不大,B位点与急性排斥反应有关,DR位点IM可致急性排斥反应明显增加。结论:在临床采用氨基酸残基配型标准判断组织配型的同时,IM不容忽视,HLA-B位点IM与肾移植术后急性排斥反应相关,HLA-DR位点IM明显影响肾移植术后排斥反应发生率。  相似文献   

3.
环孢素结合蛋白A mRNA表达与移植肾急性排斥的关系   总被引:2,自引:0,他引:2  
目的观察肾移植患者环孢素结合蛋白A(CvPA)mRNA表达水平与血环孢素(CsA)浓度和急性排斥的关系.方法采用逆转录聚合酶链反应动态测定23例肾移植稳定患者和10例急性排斥患者的移植肾活检标本及外周血淋巴细胞中CvPA mRNA的表达.结果应用CsA后肾功能稳定患者,CyPA的表达水平,在淋巴细胞(P=0.013)和肾组织(P=0.038)均显著上升,而急性排斥患者则无明显变化(P>0.05);淋巴细胞中CyPA的表达与CsA浓度存在低度相关性(r=0.384,P=0.047);急性排斥患者淋巴细胞中CyPA表达水平低于肾功能稳定者(P=0.009).结论应用CsA预防排斥的肾移植患者淋巴细胞中CyPA低表达是导致排斥发生的可能因素之一.对淋巴细胞CyPA表达水平进行监测,并结合CsA血浓度,有可能指导CsA的合理应用.  相似文献   

4.
应用荧光偏振免疫法(FPIA)对30例高危尿毒症患者肾移植术后早期的全血环孢素A(CsA)浓度进行动态监测。结果表明:高危尿毒症患者肾移植术后早期的全血CsA浓度明显高于对照组,术后早期急性排斥反应的发生率低,但是容易发生CsA的肝脏及胰腺的毒副作用。本资料分别探讨了不同高危受者术后应用CsA免疫抑制治疗的特点。  相似文献   

5.
目的 研究在移植肾功能稳定的受者中主动撤除环孢素A(CSA)对急性排斥反应发生率及肾功能的影响.方法 选择35例肾功能稳定的肾移植受者,其中尸体肾移植23例,亲属活体肾移植12例.除2例为再次肾移植外,其余均为初次肾移植.分别在肾移植术后6个月~6年时停用CsA,平均为术后(13.3±9.1)个月.撤除CsA后免疫抑制方案为:霉酚酸酯(MMF)+西罗莫司(SRL)+泼尼松(Pred).撤除CsA前有9例做了移植肾穿刺活检,8例测定了抗HLA抗体.结果 对35例受者随访6个月~4.5年,平均14.8个月.撤除CsA前、后血肌酐平均值分别为(88.1±15.5)μmol/L和(92.3±23.7)/μmol/L(P0.05).撤除CsA后,有2例经活检证实发生急性排斥反应,治疗后均逆转;CsA所致的毒副作用,如牙龈增生、糖耐量异常和多毛症等明显改善.9例移植肾活检中,有3例肾功能正常的受者已出现轻度慢性移植肾肾病表现.抗HLA抗体检测中,7例阴性者在撤除CsA前、后肾功能无明显变化.1例抗HLA抗体呈强阳性者在撤除CsA后进展为慢性移植肾肾病,恢复血液透析.结论 对移植肾功能稳定的受者在移植6个月后撤除CsA,转换为"霉酚酸酯+西罗莫司+泼尼松"的免疫抑制方案是安全的,不增加急性排斥反应风险;撤除CsA有利于消除一些与其相关的毒副作用;对抗HLA抗体呈强阳性者.撤除CsA后很难改变肾功能的进展.  相似文献   

6.
他克莫司替代环孢素A治疗难治性排斥   总被引:1,自引:1,他引:0  
目的:观察他克莫司(FK506)替代环孢素A(CsA)治疗肾移植后难治性急性排斥反应的有效性及安全性。方法:10例肾移植患者术后使用CsA,发生急性排斥反应后给予皮质激素冲击和单克隆抗体或抗胸腺细胞球蛋白,治疗无效后,停用CsA,开始给予FK506,服药1周后,根据血中FK506的浓度调整其用量,维持血中FK506的浓度为9-12ug/L。结果:10例患者中有9例急性排斥得到逆转,肾功能恢复正常,1例无效,随访50-350d,9例肾功能恢复者保持持续稳定,结论:FK506替代CsA治疗肾移植术后难治性急性排斥反应是安全,有效的。  相似文献   

7.
目的 探讨肾移植受者外周血单个核细胞(PBMC)上Notch1受体表达水平与移植肾排斥反应之间的关系.方法 肾移植受者40例均采用环孢素A(或他克莫司)、吗替麦考酚酯和糖皮质激素预防排斥反应.根据移植肾穿刺活检结果(Banff'97标准)将受者分成3组,其中急性排斥反应组11例,钙调磷酸酶抑制剂(CNI)中毒组16例,肾功能稳定组13例,抽取血液样本;急性排斥反应组中有8例于排斥反应逆转后再次抽取血液样本;另取11名正常人的血液样本作为对照.常规提取样本中PBMC,用流式细胞仪间接荧光法检测Notch1的表达水平.结果 急性排斥反应组受者外周血PBMC上Notch1的荧光强度明显高于CNI中毒组、肾功能稳定组和正常对照组(P<0.05).CNI中毒组、肾功能稳定组和正常对照组荧光强度的差异无统计学意义(P>0.05).40例受者外周血PBMC上Notch1的荧光强度为2.60±2.37,血肌酐为(241.2±137.1)μmol/L,二者之间存在相关性(r=0.358,P<0.05).急性排斥反应组受者排斥反应逆转后的Notch1的荧光强度低于排斥反应期间,差异有统计学意义.结论 肾移植受者急性排斥反应期间外周血PBMC上Notch1受体表达水平增高.Notch1可做为监测肾移植受者免疫状态的指标,其表达水平与同期肌酐水平有相关性,可在一定程度上反映排斥反应对肾功能的损害程度.  相似文献   

8.
肾移植受者血清IgE和SIL—2R的监测价值   总被引:3,自引:0,他引:3  
本文通过肾移植受者血清IgE和SIL-2R水平的动态监测,观察术后排斥反应、并发感染、环孢素A(CsA)肾中毒时的浓度变化。发现它们是了解移植肾功能状态的快速、简便、无创伤性的理想指标。肾移植患者53例,男36例,女17例,年龄22~58岁,平均36.2岁。供受者ABO同血型,淋巴毒性试验平均5.3%,术后常规应用三联免疫抑制剂,环孢素A、硫唑嘌呤、泼尼松。IgE和SIL-2R测定时间为:术前1天,术后第1周每天1次,策2周起每周2次,怀疑排斥、感染或CsA肾中毒时,立即取患者血清测定。测定结果见附表。从表中可见,术前尿毒症组IgE与…  相似文献   

9.
目的 探讨服用微乳化环孢素A(CsA)的长期存活肾移植受者血CsA浓度监测的意义。方法 回顾性分析126例存活1年以上的肾移植患者术后血CsA浓度的资料,入选受者术后存活1~17年,随访期间患者均接受微乳化CsA、霉酚酸酯(或硫唑嘌呤)及泼尼松预防排斥反应,CsA浓度测定采用免疫荧光偏振TDx法。分析服药后2h血CsA浓度(C2)变化及其与药物剂量、移植肾功能之间的关系。结果 C2随术后时间的延长逐渐降低,但个体间的变异度随时间延长而逐渐加大;肾移植后的前5年,C2与服药剂量以及移植肾功能呈显著正相关关系,肾移植后10年以上的受者C2与肾功能关系不明显。结论 对于存活1年以上的肾移植受者,C2仍然是药物凋控的一个有效指标,但随移植时间的延长,C2的变异度逐渐加大。  相似文献   

10.
两种免疫抑制方案在乙肝病毒感染的肾移植受者中的应用   总被引:2,自引:0,他引:2  
目的:比较乙肝病毒感染的肾移植受者应用普乐可复(FK506)或环孢素A(CsA)为基础的两种免疫抑制方案的抗排斥疗效及肝损害情况.方法:将乙肝病毒感染的肾移植受者随机分为FK506组和CsA组,每组各20例,两组均联合应用霉酚酸酯(MMF)和泼尼松(Pred).结果:观察12个月,FK506组中有3例(15%)患者发生急性排斥,CsA组中有4例(20%)发生急性排斥,均使用甲基泼尼松龙(MP)冲击治疗后逆转,两组急性排斥发生率差异无统计学意义.FK506组中有4例(20%)出现肝损害,CsA组中有14例(70%)出现肝功能异常,两组肝功能损害发生率差异有统计学意义.结论:FK506免疫抑制效果与CsA相似,但对肝功能影响较小,适合作为乙肝病毒感染的肾移植受者首选的免疫抑制剂.  相似文献   

11.
目的 探讨HLA-G的表达水平与肾移植术后急性排斥反应(AR)和巨细胞病毒(CMV)活动性感染的相关性.方法 根据术后是否发生AR或CMV活动性感染,将132例初次肾移植受者分为肾功能稳定组、AR组和CMV组.另选择41例健康供者作为对照组.采用流式细胞术、酶联免疫吸附试验、蛋白质印迹法以及实时定量聚合酶链法检测各组HLA-G及其mRNA的表达,并采用免疫组织化学法观察移植肾组织中HLA-G的表达.结果 肾移植前后各组膜结合型HLA-G1 (mHLA-G1)的表达均处于较低水平,仅术后CMV组mHLA-G1+的中性粒细胞出现显著升高(P<0.05).术前可溶性HLA-G5(sHLA-G5)的表达水平肾功能稳定组显著高于对照组(P<0.05);术后sHLA-G5的表达水平CMV组显著高于肾功能稳定组(P<0.05),而肾功能稳定组均高于对照组和AR组(P<0.05),AR组与对照组的差异无统计学意义(P>0.05).术后CMV组sHLA-G5 mRNA的表达水平最高(P<0.05),肾功能稳定组次之,对照组和AR组均较低.21例AR组移植肾组织活检样本中,17例HLA-G表达呈阴性,3例呈阳性,1例呈弱阳性;9例CMV组移植肾组织活检样本的HLA-G表达均为阳性.132例受者中,28例CMV感染者的AR发生率为7.1%(2/28),104例非CMV感染者的AR发生率为25.0%(26/104),二者间AR发生率的差异有统计学意义(P<0.05).结论 sHLA-G5可作为预测AR和CMV感染的生物标志分子;CMV感染和AR与受者体内的免疫平衡状况相关.  相似文献   

12.
13.
目的探讨肾移植术后中远期移植肾急性排斥反应(AR)发生影响因素及移植肾生存情况。 方法回顾性分析浙江大学医学院附属第一医院肾脏病中心2018年1月至2019年12月因血清肌酐水平升高而接受移植肾病理活检并确诊移植肾AR受者临床资料,共纳入43例受者,其中急性抗体排斥反应组17例,急性T细胞排斥反应组26例;同时纳入同期(2周内)肾移植且移植肾功能正常的39例受者为对照组。正态分布计量资料比较采用配对t检验或单因素方差分析。计数资料比较采用χ2检验或Fisher确切概率法。采用Kaplan-Meier进行生存分析,并采用log-rank进行比较。P<0.05为差异有统计学意义。 结果急性抗体排斥反应组HLA-A错配2个比例(4/17)高于对照组(1/39),差异有统计学意义(P=0.026)。急性抗体排斥反应组和急性T细胞排斥反应组AR发生时和末次血清肌酐和估算肾小球滤过率(eGFR)均高于AR发生前(P均<0.05);急性抗体排斥反应组和急性T细胞排斥反应组AR发生时和末次血清肌酐和eGFR均高于对照组(P均<0.05);急性抗体排斥反应组进入慢性肾脏病(CKD)-4期受者比例低于急性T细胞排斥反应组(χ2=5.73,P<0.05);急性T细胞排斥反应组进入CKD-4期受者比例以及急性抗体排斥反应组移植肾失功比例均高于对照组(χ2=17.727和9.882,P均<0.05)。AR发生时急性抗体排斥反应组和急性T细胞排斥反应组受者均接受PRA检测,前者PRA-Ⅰ和PRA-Ⅱ阳性比例分别为41.2%(7/17)和88.2%(15/17),均高于后者[11.5%(3/26)和26.9%(7/26)],差异均有统计学意义(P=0.042,P<0.001)。急性抗体排斥反应组、急性T细胞排斥反应组及对照组术后分别有13、24和38例受者应用他克莫司。发生AR时,急性抗体排斥反应组他克莫司血药浓度[(3.72±0.76)ng/mL]与急性T细胞排斥反应组[(3.37±0.86)ng/mL]均低于对照组[(5.73±1.25)ng/mL],差异均有统计学意义(P均<0.05);急性抗体排斥反应组与急性T细胞排斥反应组他克莫司血药浓度均低于发生AR前[(6.27±1.18)和(6.33±1.63)ng/mL],差异均有统计学意义(t=7.120和6.216,P均<0.05)。急性抗体排斥反应组4例受者应用以环孢素为基础的免疫抑制方案,其中3例术后33、36和55个月环孢素血浓度分别为112.4、138.3和7.0 ng/mL,均低于要求血药浓度。急性T细胞排斥反应组2例应用环孢素受者术后16和177个月环孢素血药浓度分别为43.2和24.6 ng/mL,均低于要求血药浓度。随访至2021年6月30日,急性抗体排斥反应组移植肾生存率低于对照组(χ2=8.738,P<0.05)。 结论HLA-A位点错配及他克莫司低血药浓度是肾移植术后中远期诱发AR的重要原因。急性抗体介导排斥反应是移植肾生存重要影响因素。  相似文献   

14.
Because of the role of P-glycoprotein (P-gp) in multidrug resistance (MDR), it has been suggested that P-gp might play a role in acute and chronic rejection after organ transplantation. The purpose of the present work was to investigate a possible relationship between graft outcome and P-gp expression on peripheral mononuclear cells of renal transplant recipients. We determined P-gp expression in 27 patients with long-term, stable graft function (ST) and in 15 patients with chronic deterioration of graft function (CR). In addition, 40 patients were studied prior to, and at intervals after, transplantation with 21 healthy individuals serving as controls. P-gp values were highest in healthy controls and in ST patients. We found no correlation between P-gp values and acute rejection. CR patients tended to have lower levels of P-gp expression. Our results contradict the opinion that an overexpression of P-gp induces acute or chronic rejection by inhibiting the efficacy of immunosuppressive treatment. Received: 9 June 1998 Accepted: 25 September 1998  相似文献   

15.
《Transplant immunology》2007,17(3-4):172-175
Adhesion molecule expression is an important event during early transplant failure. The aim of the present study was to examine the release of adhesion molecules during the first minutes of kidney allograft reperfusion in relation to delayed graft function and acute graft rejection. We enrolled 49 renal transplant recipients, including 13 cases of delayed graft function (DGF) and 11 cases of acute graft rejection (AR).Plasma concentrations of E-selectin, VCAM-1 and ICAM-1 after 3 min of reperfusion were significantly higher than in the iliac vein before reperfusion. There was no statistically significant difference between patients with and without DGF as regards E-selectin, VCAM-1 and ICAM-1 concentrations in the iliac vein before and in the renal vein after 3 min of reperfusion.Concentrations of adhesion molecules in the iliac vein before reperfusion and in the renal vein after 3 min of reperfusion did not differ significantly between patients with and without AR except for ICAM-1 iliac vein concentration which was significantly increased in AR patients. Plasma levels of E-selectin, ICAM-1 and VCAM-1 were increased after kidney allograft reperfusion. Moreover, elevated serum levels of ICAM-1 before transplantation correlated with subsequent acute kidney allograft rejection.The results suggest that elevated ICAM-1 levels may be implicated in acute graft rejection.  相似文献   

16.
Noninvasive biomarker profiles of acute rejection (AR) could affect the management of liver transplant (LT) recipients. Peripheral blood was collected following LT for discovery (Northwestern University [NU]) and validation (National Institute of Allergy and Infectious Diseases Clinical Trials in Organ Transplantation [CTOT]‐14 study). Blood gene profiling was paired with biopsies showing AR or ADNR (acute dysfunction no rejection) as well as stable graft function samples (Transplant eXcellent—TX). CTOT‐14 subjects had serial collections prior to AR, ADNR, TX, and after AR treatment. NU cohort gene expression (46 AR, 45 TX) was analyzed using random forest models to generate a classifier training set (36 gene probe) distinguishing AR vs TX (area under the curve 0.92). The algorithm and threshold were locked and tested on the CTOT‐14 validation cohort (14 AR, 50 TX), yielding an accuracy of 0.77, sensitivity 0.57, specificity 0.82, positive predictive value (PPV) 0.47, and negative predictive value (NPV) 0.87 for AR vs TX. The probability score line slopes were positive preceding AR, and negative preceding TX and non‐AR (TX + ADNR) (≤ .001) and following AR treatment. In conclusion, we have developed a blood biomarker diagnostic for AR that can be detected prior to AR‐associated graft injury as well a normal graft function (non‐AR). Further studies are needed to evaluate its utility in precision‐guided immunosuppression optimization following LT.  相似文献   

17.
目的评价白细胞介素15(IL-15)mRNA测定在肝移植术后早期急性排斥反应诊断及其与感染鉴别诊断中的价值。方法共43例原位背驮式肝移植患者,术后1个月内,应用逆转录聚合酶链反应技术连续检测胆汁和血清中IL-15mRNA的表达情况,胆汁和血送细菌培养。排斥反应均经病理切片证实。结果16例发生急性排斥反应(排斥组),12例发生感染(感染组),其余15例没有发生并发症(正常组)。在急性排斥反应和感染确诊前,排斥组62.5%胆汁IL-15mRNA表达阳性,这一比例明显高于感染组的16.7%和正常组的13.3%(P〈0.叭);当排斥反应和感染确诊时,排斥组胆汁IL-15mRNA表达阳性的患者比例上升至87.5%,感染组为25.0%;采取相应措施治疗3d后,排斥组表达阳性的患者比例下降至18.8%,感染组为25.0%。外周血IL-15mRNA表达阳性率,在急性排斥反应和感染确诊前,排斥组和感染组分别为37.5%和41.7%;诊断确立后,这一比例上升至68.8%和75.0%;治疗后两组IL-15mRNA表达阳性率迅速下降,排斥组和感染组各检测时相的外周血IL-15mRNA表达阳性率的差异均无统计学意义。结论检测胆汁中IL-15mRNA的表达不仅有利于术后早期急性排斥反应的诊断,还有助于其与感染的鉴别诊断及抗排斥治疗的疗效判断。  相似文献   

18.
BACKGROUND: Nitric oxide (NO) is produced by nitric oxide synthases (NOS), which are either constitutively expressed in the kidney or inducible, in resident and infiltrating cells during inflammation and allograft rejection. NO is rapidly degraded to the stable end products nitrite and nitrate, which can be measured in serum and urine, and may serve as noninvasive markers of kidney allograft rejection. METHODS: Total nitrite and nitrate levels (NOx) were measured in serum and urine thrice weekly after an overnight fast in 18 consecutive patients following renal cadaveric transplantation. Inducible NOS (iNOS) and endothelial NOS (eNOS) expression was immunochemically determined in renal biopsy specimens with or without acute rejection (AR). RESULTS: Serum NOx levels increased days before AR and were significantly higher at the moment of AR (27+/-12.4 micromol/L) compared with recipients with an uncomplicated course (13+/-7.6 micromol/L), but not compared with recipients with cyclosporine (CsA) toxicity (20+/-13.0 micromol/L). Urinary NOx levels were significantly lower during AR (20+/-13.6 micromol/mmol creatinine) compared with an uncomplicated course (64+/-25.2 micromol/mmol creatinine) or CsA toxicity (53.8+/-28.3 micromol/mmol creatinine). Interstitial and glomerular iNOS expression was significantly increased in biopsy specimens showing AR. Unexpectedly, glomerular eNOS expression was significantly decreased in patients with AR. CONCLUSIONS: This study reports differences in NOx levels in serum and urine, which may help discriminate AR episodes from an uncomplicated course or CsA toxicity. As expected, renal iNOS expression is increased in acute allograft rejection. The decrease in glomerular eNOS expression suggests an intriguing link between acute and chronic rejection.  相似文献   

19.
Copy number variation (CNV) in gene was a novel type of genetic diversity in human that affect the pathogenesis, progress, and prognosis of disease. The aim of this study was to determine the associations between CNV in CCL3L1 gene and the rejection risk in liver-transplant recipients. The 266 Han-Chinese patients and 135 volunteers were enrolled in this study. Genomic DNA and mRNA samples were obtained from the whole peripheral blood; a quantitative real-time PCR-based assay was carried out to determine the copy number of CCL3L1, and real-time PCR was carried out to calculate the CCL3L1/CCL3 mRNA ratio. The CNV distributions in patients and health controls had no significant differences. Copy number in acute rejection group (AR) shifted to higher number compared with non-acute rejection group (4.74±1.87 vs. 3.88±2.13, p=0.017). Moreover, patients with higher CCL3L1 copies (≥3 copies) had a significantly higher rejection risk than patients lower copies CCL3L1 (OR=3.85, 95% CI, 1.14-13.04; p=0.021). No association was found between CNV and rejection grades. In conclusion, liver transplant recipients with high copy number of CCL3L1 gene had a significant higher risk of AR. CNV might be a novel genetic diversity that correlated with allograft rejection.  相似文献   

20.
Circulating adhesion molecules during kidney allograft reperfusion   总被引:3,自引:0,他引:3  
Adhesion molecule expression is an important event during early transplant failure. The aim of the present study was to examine the release of adhesion molecules during the first minutes of kidney allograft reperfusion in relation to delayed graft function and acute graft rejection. We enrolled 49 renal transplant recipients, including 13 cases of delayed graft function (DGF) and 11 cases of acute graft rejection (AR). Plasma concentrations of E-selectin, VCAM-1 and ICAM-1 after 3 min of reperfusion were significantly higher than in the iliac vein before reperfusion. There was no statistically significant difference between patients with and without DGF as regards E-selectin, VCAM-1 and ICAM-1 concentrations in the iliac vein before and in the renal vein after 3 min of reperfusion. Concentrations of adhesion molecules in the iliac vein before reperfusion and in the renal vein after 3 min of reperfusion did not differ significantly between patients with and without AR except for ICAM-1 iliac vein concentration which was significantly increased in AR patients. Plasma levels of E-selectin, ICAM-1 and VCAM-1 were increased after kidney allograft reperfusion. Moreover, elevated serum levels of ICAM-1 before transplantation correlated with subsequent acute kidney allograft rejection. The results suggest that elevated ICAM-1 levels may be implicated in acute graft rejection.  相似文献   

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