Rapamycin instead of mycophenolate mofetil or azathioprine in treatment of post-renal transplantation urothelial carcinoma

Background Malignant tumor is the most common complication occurred in transplant recipients. It is widely recognized that immunosuppressive treatments increase the risk of cancer in transplant recipients. The efficacy and safety of rapamycin （RPM） in combination with low-dose calcineurin inhibitor （CNI） in treating 15 renal allograft recipients which developed urothelial carcinoma were observed.
Methods Immunosuppressive regimen in all recipients was altered with rapamycin to replace mycophenolate mofetil （MMF） or azathioprine （Aza）. The initial loading dosage was 2 mg/d, and the next dosage was 1 mg/d. The dosage of rapamycin was carefully adjusted according to the blood drug level and concentration of the drug was maintained at 4-6 μg/L. In all the 15 patients, the calcineurin inhibitor was reduced down to one third of the original dosage after the rapamycin blood concentration became stable. Surgical treatment and intravesical instillation chemotherapy were carried out in all patients. Recurrence of the tumor was monitored throughout the study. Post-transplant renal function and side effects were also closely monitored.
Results Among the 15 patients, 9 had no tumor recurrence in 2 years, 2 had tumor recurrences twice, and 4 had once. There was no acute rejection observed during RPM treatment. Post-transplant renal function in 11 patients was improved with a decreased creatinine level. Hyperlipoidemia and thrombocytopenia were the most frequent adverse events which responded well to corresponding treatments.
Conclusion Among the renal allograft recipients with urothelial carcinoma, combination of rapamycin and low dose calcineurin inhibitor treatment is effective and safe.     

Daclizumab prevents acute renal allograft rejection. 1 year analysis

Objective To investigate the clinical effect of Daclizumab on preventing acute rejection in renal transplant recipients.Methods71 patients were randomly divided into two groupsDaclizumab group (n =26) and control group (n = 45). Baseline regimen of mycophenolate mofetil (MMF), cyclosporin (CsA), methylprednisolone (MPD) and prednisone (Pred) were administered to all patients. The treatment of Daclizumab was based on baseline regimen. The Daclizumab group received Daclizumab twice before and after renal transplant. The occurrence of post-transplantation acute rejection, renal function and T lymphocyte subtypes were sequentially monitored; meanwhile adverse events, infection episode, and patient and graft survival were observed.All of patients received a follow-up of 12 months at least. Results The occurrence of acute rejection in Daclizumab group in 1,3, 6 and 12 months after renal transplantation was 7.7%, 19.2%, 23.1% and 30.8%, respectively,while it was 15.6% ,28.9%,35.6% and 46.7% in the control group. There was significant difference between the two group(P ＜ 0.05). There was no difference in infection episodes and adverse events between the Daclizumab group and control group. One year patient survival was 92.3% in Daclizumab group, 91.1% in control group (P ＞ 0.05), compared with graft survival of 96.2 % and 93.3 % for Daclizumab and control group, respectively (P ＞ 0. 05). The renal function in Daclizumab group in 1, 6 and 12 months after renal transplantation was better than that in control group (P ＜ 0.05). The CD3 and CD4 subtypes decreased in both two groups after operation but no significant difference (P ＞ 0.05). ConclusionDaclizumab combined with MMF, CsA, MPD and Pred therapeutic regimen was effective to reduce the occurrence of acute rejection in renal transplant recipients and have no influence on T lymphocyte subtypes.     

Oinincal study on increased Mood concentration of cyclosporin A influenced by nicadipine in renal transplantation recipients

Objective To study the effect of nicadipine on blood pressure (BP) and blood trough level concentration of cyclosporin A ( CsA) in renal transplantation recipients. Methods Sixty-two cases of renal transplantation recipients in the study group whose renal function had recovered to be normal were treated with CsA. and nicadipine, and 23 cases of renal transplantation recipients in the control group were treated with CsA and nifedipine. Hood trough levels and dose of CsA.serum creatinine(SCr) and BP were determined and served as indicators of clinical evaluation. Results After the treatment of nicadipine, the blood trough level of CsA was increased significantly, and BP was decreased and kept within normal range. Furthermore, the dose of CsA was reduced by 34.2% 6 months later compared with that before the treatment(P<0.01). No significant effects on renal function were observed before and after the treatment. Conclusion Nicadipine is safe and effective for the treatment and prevention of hypertension aft     

Sirolimus as primary immunosuppression for calcineurin inhibitor-related renal insufficiency following liver transplantation

Objective To evaluate efficiency and safety of sirolimus in preserving renal function in patients with renal insufficiency by tacrolimus after liver transplantation. Methods was used in 13 patients after liver transplantation. Patients with a creatinine levcl higher than 132.6μmol/L were eligible for conversion to sirolimus.     

The mid-long term effect of conversion from cyclusporine to trcrolimus in patients with kidney

<正>Objective To verify the efficacy and safety of conversion from cyclosporine ( CsA) to tacrolimus ( Tac) in renal transplant recipients. Methods The clinical data of conversion from CsA to Tac in renal transplant recipients were retrospectively analyzed. In 97 petients undergoing kidney transplantation,there were 62 cases of chronic al-     

Rapamycin increased development of CD4~+ CD25~h ighFoxp3~+ T cells of peripheral blood in liver transplant recipients

<正>Objective To investigate the possible influence of immunosuppressive therapy,including sirolimus ( SRL) and calcineurin inhibitors ( CNI,tacrolimus) ,on level of Treg in liver allo - graft recipients. Methods Forty - seven liver transplant recipients with stable liver function were assessed for at least 2 years,and divided into two     

Use of PCR and PCR-SSP for detection of urinary donor-origin DNA in renal transplant recipients with acute rejection

Objective To analyze the urine of renal recipients for the pressence of donor DNA in an attempt to establish an alternative diagnostic means of acute rejection.Methods Sixty-four renal transplant recipients were examined.Thirty-seven were normal after transplantation,while 22 others developed acute rejection,based on serum creatinine levels and/or needle biopsy findings of the graft.Five developed drug-induced renal dysfunction.In female recipients with a male graft,we examined urine for the presence of Ychromosome(SRY and DYZ-1) and in recipients receiving and HLA mismatched graft,we looked for HLA-DR gene(DRB1)using PCR.Results Among the 14 female recipients with male grafte demonstrating stable renal function,only one was positive for SRY and DYZ-1 on the Y chromosome.However,sry AND DYZ-1 were found in the urine of four female patients with acute rejection,but these DNA fragments were not detected in 3 of the 4 after anti-rejection therapy.The last patient was referred to hemodialysis.Of 23 recipients of a graft from HLA mismatch donors with stable renal function,DRB1 was negative in 21(91%).Of 18 patients with acute rejection,DRB1 was positive in 16(89%)and negative in 2.these ENA fragments were no longer found in 13 patients after anti-rejection therapy.In all patients with drug induced renal dysfunction,donor-derived DNA was negative.Conclusions Presence of door specific DNA in the urine of the recipient is strongly associated with acute rejection.Analysis of dna DNA derived from donor cells in urine was an effective and accurate method for the diagnosis of acute rejection of a renal transplant.     

Determination of ATP in CD4^＋ cells in renal transplant recipients and implication

Objective To investigate the association of post-transplant diabetes mellitus （PTDM） in kidney transplant recipients with HLA-DR . DQ genes. Methods Retrospective analyses on 160 cases of kidney transplant recipients were carried out. There were 28 cases of PTDM and 132 cases of non-PTDM who were HLA-typed before renal transplantation. Compated with non-PTDM,     

Protein A immunoadsorption combined with rituximab in highly sensitized kidney transplant recipients

Background The number of highly sensitized patients is rising, and sensitization can lead to renal transplant failure. The present study aimed to investigate the safety and efficacy of protein A immunoadsorption combined with rituximab （RTX） in highly sensitized recipients of kidney transplants.
Methods Seven highly sensitized recipients of living-related renal transplants （4 men and 3 women, mean aged 42.5 years old （range 33-51）） were pretreated with this combination. Human leukocyte antigen （HLA） mismatch number was 2-5. Panel reactive antibody （PRA） of class Ⅰwas high in 2 cases and that of class Ⅱwas high in 1 case. All patients were pretreated with immunoadsorption 2-10 times. Immunoglobulin and PRA changes were monitored before and after absorption. The operation was conducted when PRA or immunoglobulin levels were at or below normal levels. Immunosuppressive drugs were provided 3-5 days before the operation, and one dose of RTX （375 mg/m^2） was infused with polyclonal antibody on the day of operation. Postoperative creatinine （Cr）, creatinine clearance rate （Ccr）, PRA ratio, and immunoglobulin changes were monitored.
Results All 7 patients had good recovery without delayed graft function. Acute rejection occurred in 3 cases at postoperative days 8, 10, and 14, respectively. The Banff 07 biopsy grades were la in 1 case and lla C4d0 in 2 cases. Successful reversion was achieved after giving methylprednisolone or antithymocyte immunoglobulin ＋ cyclophosphamide. All patients were discharged with normal renal function, mean class Ⅰ PRA was 14% and mean class ⅡPRA was 35%. PRA was completely negative in 3 cases.
Conclusion Protein A immunoadsorption combined with RTX can safely reduce the occurrence of humoral rejection in highly sensitized renal transplant recipients.     

Liver

208168 Effect of progtaglandin E1 on renal blood flow and serum endothelin in early stage after liver transplanta-tion/Qi Xiaosheng(戚晓升,Dept Gener Surg,1st Peop Hosp Shanghai,Shanghai 200080)…∥Chin J Organ Transplant.-2007,28(8).-451～453Objective To assess the effect of prostaglandin E1(PGE1) on renal blood flow and serum endothelin of liver recipients.Methods PGE1 was administered in 38 liver recipients at the dose of 0.6 μg·kg-1·h-1 during liver transplantation and every day after operation.The effects of PGE1 on serum endothelin concentration and cratinine (Cr) were observed and these indexes were compared with those in the control group (n=18).The renal blood flow resistance indexes (RI) were measured by Doppler ultrasound.     

慢性移植肾肾病患者西罗莫司替代钙调磷酸酶抑制剂对肾功能的影响

目的 观察慢性移植肾肾病(CAN)患者采用西罗莫司(SIR)替代钙调磷酸酶抑制剂(CNI)治疗的疗效和安全性.方法 前瞻性、开放性、非随机对照研究,2004年1月至2006年6月浙江大学医学院附属第一医院肾脏病中心诊断CAN患者74例,基线估算的肾小球滤过率(eGFR)为30～60ml·min-1·(1.73 m2)-1.其中36例采用SIR切换治疗(CNI药物停用12 h后开始使用SIR),另外38例继续使用CNI药物维持治疗(环孢素治疗30例;他克莫司治疗8例).所有患者霉酚酸酯适当加量并随访4年,定期观察移植物肾功能和eGFR,记录排斥反应等不良事件的发生情况,监测血常规、血脂、肝功能等指标.结果 SIR切换组和CNI维持组切换前eGFR分别为(40±7)ml·min-1·(1.73 m2)-1和(38±6)ml· min-1· (1.73 m2)-1,差异无统计学意义(P＞0.05).切换后SIR切换组较CNI维持组移植肾功能改善明显,在随访至3、12、24、36和48个月时SIR切换组eGFR均明显高于CNI维持组(均P＜0.05).随访结束时SIR切换组发生急性排斥反应2例,蛋白尿1例,肺部感染1例;CNI维持组发生急性排斥反应2例(P＞0.05).以肌酐翻倍作为终点事件显示SIR切换组的4年存活率(75.0％)显著优于CNI维持组(50.0％)(P=0.03).随访3个月时SIR切换组血总胆固醇和甘油三酯均显著高于切换前;总胆红素显著低于切换前和CNI维持组(均P＜0.05).结论 SIR替代CNI药物治疗CAN患者可以明显改善移植肾肾功能,提高移植肾长期存活,同时并不增加排斥风险.     

肾移植术后应用普乐可复(FK506)逆转环孢素A(CsA)引起肝功能损害的临床研究

目的 :观察普乐可复 (FK5 0 6 )替换环孢素A(CsA)在防治尸肾移植术后药物性肝损害的有效性和安全性。方法 :选择 2 5例尸肾移植术后应用CsA出现肝功能异常而肾功能正常患者 (移植术后 2个月～ 36个月 ,年龄 2 3岁～ 5 8岁 ) ,以FK5 0 6切换CsA ,FK5 0 6初始剂量及维持剂量以患者体重、移植后时间、病情及全血FK5 0 6血药浓度进行相应调整 ,同时予以保肝治疗。结果 :将CsA切换成FK5 0 6治疗 2周～ 4周后 ,患者肝功能指标 (血清ALT、D BIL及I BIL)呈明显下降趋势。 8周～ 10周后 ,19例患者肝功能恢复正常 ,6例接近正常 ,换药前后比较差异有显著性 ,P <0 0 5。肾功能 (血清Cr、BUN)换药前后比较差异无显著性 ,P >0 0 5。以上病例继续随访 3个月～ 6个月 ,肝功能、肾功能全部维持正常。结论 :对CsA引起肝功能损害的尸肾移植患者应用FK5 0 6替换治疗是安全有效的。     

伐地那非联合心理疗法治疗老年男性肾移植受者勃起功能障碍的疗效评价

目的：评估伐地那非联合心理疗法治疗老年男性肾移植受者勃起功能障碍（ED）的有效性及安全性。方法：随机选取50岁及以上、肾移植术后1年及以上和血肌酐150 μmol?L-1的肾移植受者120例，应用国际勃起功能指数（IIEF）进行肾移植术后性功能状况评分，存在ED者给予伐地那非联合心理治疗6个月，重新采用IIEF来评估其有效性。监测患者血清肌酐值、肌酐清除率、肝功能及免疫抑制剂（环孢素及普乐可复）浓度以评估伐地那非的安全性。结果：120例肾移植受者中78例存在ED。78例ED患者采用伐地那非联合心理治疗6个月后，IIEF评分由11.2±4.2升至23.3±4.6（P<0.05）；肾功能、肝功能及免疫抑制剂浓度在治疗前后无明显改变，无严重不良反应。结论：伐地那非联合心理疗法治疗老年男性肾移植术后ED有效且安全。     

西罗莫司转换对超米兰标准肝癌肝移植患者肿瘤复发的影响

[目的] 研究西罗莫司为基础的免疫抑制方案对超出米兰标准肝癌肝移植患者的生存率及肿瘤复发的影响。 [方法] 回顾性分析2010年6月到2011年6月我院器官移植科22例超米兰标准的肝癌肝移植患者,对他克莫司治疗组（CNIs）和转换为西罗莫司（SRL）治疗组进行资料分析。计量资料采用t检验,无复发生存率用Kaplan-Meier分析,所有数据用SPSS16.0计算,P<0.05为差异有统计学意义。 [结果] 对22例患者平均随访12±3个月（7～18个月）,两组间急性排斥反应发生率无明显差异;SRL组有4例复发,CNIs组有8例复发,Kaplan-Meier无复发生存曲线显示转换为SRL治疗的患者其肝癌无复发生存期明显高于CNIs组（P<0.05）。SRL组白细胞和血小板计数较CNIs组降低,具有统计学意义（P<0.05）。CNIs组有3例因肾损害转换为SRL治疗后肾功能均好转。SRL治疗组患者有2例发生口腔溃疡,没有发生肝动脉栓塞等严重并发症。 [结论] 西罗莫司可有效用于超出米兰标准的肝癌肝移植患者,能够取得与CNIs类似的抗排斥反应效果,同时明显降低肿瘤复发的风险。     

同种异体肾移植患者B型钠尿肽水平的临床观察

目的：探讨同种异体肾移植患者和发生急性排斥反应时血浆B型钠尿肽（BNP）水平及其临床意义。方法：采用免疫夹心化学发光法检测17例首次肾移植患者术前1d、术后第1天、第2天、第3天、1周、2周和3个月血BNP浓度。17例健康体检者作对照。结果：肾移植患者术前1d血BNP浓度显著高于健康对照组（P〈0．01）。肾移植术后血BNP浓度呈下降趋势（χ^2=14．25，P=0．027）。13例没有发生急性排斥反应的患者血BNP浓度术后1周和3个月与肾移植术前比较差异有显著性（P〈0．05）；4例发生急性排斥反应患者，发生急性排斥反应当天的血BNP浓度显著增高，加强抗排斥治疗后很快下降。结论：肾移植成功后可以降低血BNP水平，但发生急性排斥反应时血BNP浓度显著增高。因此，血BNP浓度可作为早期诊断移植肾急性排斥反应发生的敏感指标。     

肾移植术前供者特异性抗体强度对术后的体液排斥反应和移植物功能的影响

目的：研究肾移植受者的术前供者特异性抗体(donor specific antibody,DSA)与其术后发生抗体介导的体液排斥反应(antibody-mediated rejection,AMR)及移植肾功能的关系。方法：选取符合要求的肾移植受者88例。术前采用Luminex流式法对肾移植受者进行DSA检测,并将受者分为DSA阳性组(n=20)与DSA阴性组(n=68)。随访时间为2年。术后参照Banff 2005标准对移植肾病理形态进行评估分级,并观察移植肾的情况。结果： DSA阳性组与阴性组AMR发生率分别为20.0%和1.5%,移植物丢失发生率分别为15.0%和1.5%,两组比较差异均有统计学意义(分别P<0.01,P<0.05);AMR受者最高DSA的荧光指数中值(mean fluorescence intensity,MFI)较非AMR受者差异明显(P<0.01);受试者工作特征(receiver operating characteristic,ROC)曲线显示肾移植术后受者发展为AMR的最高MFI阈值为7909.5。两组移植肾功能延迟回复的发生相比较,差异无统计学意义(P>0.05)。结论：肾移植术前检测DSA水平,可以预测AMR的发生风险和移植肾功能状态。最高DSA值的MFI截点(7909.5)能够预测AMR发生的风险。     

不同程度慢性乙型肝炎患者肾脏移植术后的转归

目的：前瞻性随访观察慢性肾衰尿毒症合并不同程度的慢性乙型病毒性肝炎的患者,接受肾脏移植术后肝病转归情况。方法：开放性收集2000年8月至2002年2月39例肾脏移植患者,其中19例合并慢性乙型病毒性肝炎患者经皮肝活检组织病理学诊断,分为轻度（A组,n=8）、中度（B组,n=6）、重度（C组,n=5）肝炎3组,无肝炎组（D组,n=20）,随访观察3年,术后定期观察血肌酐（Scr）,肝功能相关指标（ALT,GGT,TB,CB,PT,A,G）,环孢霉素A（CsA）谷值,乙肝病毒学相关指标、肝纤维化指标,肝脏B超,Child-Pugh评分变化,3组中各有2例进行重复肝活检组织病理学检查。结果：A组在随访3年中各项观察指标均无明显变化。B组从术后6个月开始GGT明显高于正常水平,在随访终点时Child-Pugh评分2例升至B级,2例重复肝活检显示已处于重度病变。C组从术后6个月开始GGT持续高于正常水平,24个月开始,血清白蛋白低于正常值,球蛋白高于正常值,随访终点时,Child-Pugh评分均在B级以上,有4例呈肝硬化改变,1例发现原发性肝癌改变,存活率仅为40％。结论：不同程度的慢性乙型病毒性肝炎患者肾脏移植术后预后有一定差别,肝脏组织病理学分组具有指导手术选择的意义。     

肾移植受者外周血白细胞CMV抗原阳性细胞数及意义

【目的】探讨肾移植受者外周血白细胞巨细胞病毒(CMV)PP-65抗原阳性细胞数的变化及意义。【方法】用免疫细胞化学法检测外周血白细胞CMV-PP65抗原,术后头3个月每周1次。【结果】273例肾移植受者中124例术后检出CMV-PP65抗原阳性,初次检出CMV-PP65抗原的平均时间为(24.1±11.3)d,每5万白细胞中CMV抗原阳性细胞数均值为7.1±5.8,其中5例CMV抗原阳性细胞数超过10/5万白细胞。无症状性和症状性CMV感染受者初次检出CMV抗原阳性细胞数分别为(6.7±5.6)/5万白细胞、(10.1±9.3)/5万白细胞(P>0.05);峰值水平为(8.1±4.2)/5万白细胞、(26.3±5.7)/5万白细胞(P<0.05);分别有17例(15%)、12例(100%)患者其峰值超过10/5万白细胞(P<0.05)。抗病毒治疗中90例(72.6%)患者CMV抗原阳性细胞数进一步升高。【结论】肾移植受者在CMV感染早期病毒复制能力强,CMV抗原阳性细胞数峰值有助于预测症状性CMV感染。     

肾移植受者BK病毒感染的临床诊断及治疗

目的 探讨肾移植受者BK病毒(BKV)感染的诊断及治疗方法.方法 选取肾移植术后48个月内的患者共227例.采集其血、尿样本,行BKV尿沉渣细胞学计数与实时荧光定量PCR检测病毒拷贝.对部分肾移植受者进行移植肾活检.将尿或血中BKV DNA阳性患者80例分成干预组(51例)与对照组(29例).干预组进行调整免疫抑制剂:19例环孢素A(CsA)减量,22例他克莫司(FK506)减量,10例FK506转换成CsA;对照组不进行干预,并且密切监测急性排斥反应.干预3个月后再次检测,比较组内和组间干预前后BKV活化指标的差异.结果 227例受者的尿decoy细胞、BK病毒尿症与病毒血症的阳性率分别为33.O%、33.5%和15.4%.干预组干预后尿decoy细胞、尿和血BKV数量的中位水平均为O,明显低于干预前(5.0个/10HP,1.50 x 104拷贝/ml,0拷贝/ml,均P<0.01).对照组观察前后尿decoy细胞、血BKV数量的中位水平差异无统计学意义(6.0个/10HPvs 5.0个/10HP、0拷贝/ml vs 0拷贝/ml,均P>0.05),尿BKV数量观察结束时上升(观察前:0.79×104拷贝/ml,观察后:2.21 x104拷贝/ml,P<0.01).上述各项指标干预前后的差值在干预组与对照组间差异均有统计学意义(均P<0.05).干预过程中所有患者均未出现急性排斥反应.确诊BKV相关性肾病4例,其干预治疗后尿decoy细胞计数以及血、尿BKV DNA均明显降低,移植肾功能有所恢复.结论 定量尿沉渣细胞学检测简单、易行、敏感,可以作为BKV活化的指标,间接反映肾脏病理情况.也可检测血、尿BKV DNA了解病毒活化情况、筛查BKV相关的移植肾肾病.减少免疫抑制剂剂量或换FKS06为CsA治疗肾移植术后BKV感染效果良好.