胰肾联合移植的排斥反应

目的探讨胰肾联合移植术后的排斥反应。方法对我院施行的3例胰肾联合移植的病人，采用FK506 MMF Perid Zenapax四联免疫治疗方案，通过床边彩超及Cr、BUN、血糖等来监测移植物的排斥反应。对排斥反应采用激素冲击疗法，对激素不敏感者采用OKT3治疗。结果3例患者中有2例出现排斥反应，其发生率达66％；在出现排斥反应时，首先表现为低热、全身不适，尿量减少，血Cr、BUN升高，彩超示移植物血流阻抗升高，之后才是血糖升高。结论胰肾联合移植中，排斥反应与多种因素有关，移植肾对移植胰具有保护作用，肾脏可以作为监测胰腺排异的窗口，彩超检查可以作为筛选移植物排异反应的手段。     

胰肾联合移植中供体切取和修整的技巧

目的:总结胰肾一期联合移植中供体胰十二指肠及肾脏切取及修整的经验。方法:回顾性分析19例胰肾联合移植术中供体胰十二指肠及肾脏切取的方法与移植物的修整技巧。结果:无1例发生移植物损伤。联合移植术后9 d之内18例完全停用外源性胰岛素,空腹血糖正常，尿糖≤（+）。术后2～4 d，血肌酐和尿素氮降至正常。3例出现移植肾脏急性排斥反应，2例发生移植胰腺急性排斥反应，给予甲泼尼龙冲击治疗后恢复正常。1例术后因移植物加速排斥反应，术后11 d切除移植胰、肾。结论:胰肾联合移植手术中，供体胰十二指肠及肾脏的切取及修整是手术成功的重要因素之一。     

胰肾联合移植的排斥反应

目的　探讨胰肾联合移植术后的排斥反应。方法　对我院施行的 3例胰肾联合移植的病人 ,采用FK5 0 6 MMF Perid Zenapax四联免疫治疗方案 ,通过床边彩超及Cr、BUN、血糖等来监测移植物的排斥反应。对排斥反应采用激素冲击疗法 ,对激素不敏感者采用OKT3治疗。结果　3例患者中有 2例出现排斥反应 ,其发生率达 6 6 % ;在出现排斥反应时 ,首先表现为低热、全身不适 ,尿量减少 ,血Cr、BUN升高 ,彩超示移植物血流阻抗升高 ,之后才是血糖升高。结论　胰肾联合移植中 ,排斥反应与多种因素有关 ,移植肾对移植胰具有保护作用 ,肾脏可以作为监测胰腺排异的窗口 ,彩超检查可以作为筛选移植物排异反应的手段。     

胰肾联合移植术后并发症的防治(附四例报告)

目的探讨肠腔引流式胰肾联合移植术后并发症的防治。方法对4例胰肾联合移植的患者,通过完善术前准备,术后加强抗感染、抗凝,抑制胰液分泌,合理使用免疫抑制剂,密切观察病情变化等措施来防止并发症的发生、发展;对出现的并发症及时地采用相应的治疗措施。结果4例患者中并发巨细胞病毒性肺炎1例、急性排斥反应3例、慢性排斥反应1例,血栓形成1例,1例因肺部感染、呼吸功能衰竭于术后23d死亡,1例移植肾因慢性排斥失功能,其余并发症均治愈。结论术后并发症严重影响着胰肾联合移植的效果,胰肾联合移植术后各种并发症的防治关键在于早期预防、早期诊断、合理治疗。     

胰腺与胰肾联合移植免疫抑制剂的应用

目前已公认胰腺与胰肾联合移植是治疗Ⅰ型糖尿病(IDDM)及其并发症的安全、有效方法。移植的最终目的是彻底根治IDDM，完全停用外源性胰岛素，消除或改善糖尿病并发症，提高生活质量。由于糖尿病病变的特殊性、移植胰排斥反应发生率和移植物丢失率高以及术后免疫抑制剂引起的副作用，如：高血压、高脂血症和移植后糖尿病(PTDM)等因素，胰腺与胰肾联合移植术后免疫抑制剂的选择与应用比单纯肾移植更复杂，涉及问题更多。本文就胰腺及胰肾联合移植术后免疫抑制的临床应用及进展作一概述。     

胰十二指肠及肾一期联合移植5例报告

目的 进一步总结胰十二指肠肾一期联合移植术的经验。方法 回顾性总结4年来共实行的5例胰十二指肠肾脏一期联合移植术的方法、疗效及并发症的预防和治疗。结果 5例术后移植胰腺和移植肾均发挥了正常功能,术后第1－10d均停用胰岛素,空腹血糖在正常范围。术后并发症的发生仍很常见,部分病人出现了诸如胰周感染,脓肿,十二指肠残瘘,化学性或细菌性膀胱炎,移植胰CMV感染,代谢性酸中毒,肺部感染和急性排斥反应等1个或多个并发症。并发症经处理后大多都能得到控制。5例中有两例已分别存活4年6个月和3年5个月,1例术后3周死于移植肾急性排斥反应多器官衰竭,另2例术后至今已10－11个月仍存活较好。结论 胰十二指肠肾脏一期联合移植对治疗1型糖尿病并发晚期尿毒症具有肯定的临床疗效,较其它移植有许多优点。术后并发症的预防和正确治疗是影响病人长期存活的重要因素。     

胰腺和肾脏在联合移植中排斥反应的比较

目的:比较胰腺和肾脏在联合移植中的排斥反应.方法:以大鼠同种异体胰肾联合移植为基础,对来自同一供体的联合移植的胰腺和肾脏排斥反应进行比较分析.结果:1.肾脏间质排斥反应出现较胰腺早.程度也较胰腺重,且以早期标本为著;2.胰肾血管排斥反应分级分布相似,无显著差异;3.胰肾间质排斥反应均早于血管出现,程度也较重     

胰、肾一期联合移植五例报告

目的 总结胰、肾联合移植的临床经验。方法 为5例糖尿病合并糖尿病肾病、肾功能衰竭患者施行胰、肾联合移植术，对手术技术、术后排斥反应的防治和其它非手术并发症的处理进行总结。结果 5例患者肾功能均转为正常，其中2例分别于术后第8周和第23周各发生急性排斥反应1次，经抗排斥治疗后肾功能逆转；2例手术后2周发生纯红细胞再生障碍性贫血；1例手术后第33d因供胰动脉血栓形成切除胰腺。经1年以上观察，5例患者均健康存活，其中4例胰、肾功能良好。结论 胰、肾联合移植是目前治疗糖尿病合并糖尿病肾病的有效手段；手术操作轻柔精细及术后并发症的预防对受者存活、移植物功能的恢复有重要意义。     

胰液膀胱引流式胰肾联合移植的远期疗效分析

目的：探讨胰液膀胱引流式胰肾联合移植的远期效果及其影响因素。方法：2001年9月～2006年1月共为14例患者行同种异体胰、十二指肠及肾联合移植术。胰腺移植于右髂窝,门静脉与髂外静脉做端侧吻合,包括腹腔动脉干和肠系膜上动脉的腹主动脉片与髂外动脉做端侧吻合,肾脏同常规肾移植于左侧髂窝。十二指肠与膀胱侧侧吻合。胰液采用膀胱外引流。术后应用他克莫司加霉酚酸酯加泼尼松三联免疫抑制方案。结果：9例患者术后胰肾功能恢复良好,早期无排斥反应发生。随访18～70个月,平均34个月。存活5年以上者4例,4年以上者5例,3年以上者6例,1年以上者9例,胰肾功能良好,血糖正常,均未使用降糖药。1例因超急性排斥反应术后第2天切除移植胰腺,随访至今2年肾功能良好。4例死亡,其中3例死于心血管事件、多器官衰竭,1例因十二指肠瘘死亡。结论：仔细完善的围手术期管理、预防和及时处理并发症、合理应用免疫抑制剂是影响胰肾联合移植患者和移植物长期存活的重要因素。     

同期胰肾联合移植12例报告--德国埃森大学的经验

目的总结同期胰肾联合移植(SPK)术的治疗效果和经验。方法自2002年1月至2003年9月,以SPK术治疗胰岛素依赖型糖尿病(IDDM)合并终末期肾病(ESRD)患者12例。每例受者接受来自同一供者的胰腺和肾脏,移植肾以经典方法植入左侧盆腔,胰腺植于右下腹。1例移植胰腺静脉与受者门静脉系统吻合,11例与体静脉系统吻合。胰腺外分泌引流方法为:3例移植物十二指肠段与受者十二指肠吻合,9例与空肠上段吻合。术前应用甲泼尼龙及抗胸腺细胞球蛋白作为免疫诱导,术后以他克莫司、霉酚酸酯和泼尼松三联抗排斥药物维持。结果术后平均随访时间23个月,受者、移植胰腺和移植肾的存活率分别为100%、91.7%和91.7%。1例再次行SPK术的受者,术后出现了超急性排斥反应,且未能逆转,于术后13d切除移植物;其余11例首次行SPK术的受者中,3例(28.3%)出现急性排斥,均获成功纠治。2例受者术后移植肾功能延迟恢复,行过渡性透析。11例首次行SPK术的移植胰腺术后立即发挥了功能,分别于术后1~5d内停用胰岛素。结论同期胰肾联合移植是胰岛素依赖型糖尿病合并终末期肾病患者的一种安全而有效的治疗方法。     

Neoquadruple induction with antithymocyte globulin/azathioprine/cyclosporine/prednisolone in simultaneous pancreas and kidney transplant recipients: 8.5-year results

Ten years ago therapy with antithymocyte globulin or OKT3, azathioprine, cyclosporine, and prednisolone was the most common induction treatment for simultaneous pancreas/ kidney (SPK) recipients. Although immunosuppression was started after surgery, there was a high incidence of acute rejection episodes. In 1995, we modified the application of antithymocyte globulin and prednisolone by starting prior to reperfusion. Between 1995 and 1996, 30 patients underwent a first SPK. Prior to reperfusion, antithymocyte globulin (4-6 mg/kg body weight) and 250 mg prednisolone were administered. Intraoperatively, another 250 mg prednisolone were administered as well as intravenous azathroprine 3 mg/kg. After surgery up to 10 doses of antithymocyte globulin were administered and cyclosporine trough levels targeted to 200 to 250 ng/mL. Prednisolone was reduced gradually. After a median period of 8.5 years (range: 7.8-9.5 years) patient, pancreas, and kidney graft survival were 93.3%, 70%, and 76.7%, respectively. Sixteen acute rejection episodes were diagnosed in 11 patients (36.7%), who were treated with prednisolone bolus (n = 4), prednisolone with OKT3 (n = 8), prednisolone with antithymocyte globulin (n = 1), cyclosporine to tacrolimus conversion (n = 2), or plasmapheresis (n = 1). Two recipients died after SPK due to severe infection or carcinoma with functioning grafts. Seven further pancreas grafts were lost. Five kidney losses were observed besides the two recipients who died with functioning grafts. While previous protocols yielded a rejection incidence after SPK between 50% and 80%, we observed 60% of patients with no rejection episode during an 8.5-year median follow-up.     

胰肾一期联合移植

目的 总结胰肾联合移植治疗糖尿病并发晚期肾功能不全病人的疗效,并探讨分析术后并发症防治经验。方法 对５例糖尿病并发现期肾小功能不全者采用胰十二指肠肾一期联合移植。免疫抑掉方案采用激素,ＣｓＡ及硫唑嘌呤或激素,ＣｓＡ及骁悉三联用药。结果 联合移植后５例胰肾均发挥正常功能,病人均立即停用胰岛素,１例术后发生移植肾急性排斥以应,死于多器官功能衰竭,余４例分别发生胰周脓肿,急性胰腺炎,十二指肠瘘,血尿等并     

Historical controlled trial of OKT3 versus basiliximab induction therapy in simultaneous pancreas-renal transplantation

SUMMARY:   Simultaneous pancreas–kidney (SPK) transplant recipients are at high immunological risk of rejection. Antibody induction is beneficial but lymphocyte-depleting therapy is associated with a high incidence of side-effects. We performed a historical controlled trial to compare OKT3 versus anti-CD25 antibody (basiliximab) induction therapy with regard to patient, kidney and pancreas survival, as well as to examine for any differences in acute rejection, graft function, and infective complications. Twenty-eight consecutive SPK transplants were performed at the Monash Medical Centre between December 1997 and November 2001. Anti CD3 monoclonal antibody (OKT3) was used prior to March 2000 ( n  = 12) and basiliximab was used after ( n  = 16), both in combination with cyclosporin, mycophenolate, and prednisolone. A retrospective comparison of outcomes was performed. At 6 months, patient (100 vs 100%), kidney (91.7 vs 91.7%) and pancreas (75 vs 83.3%) survival were similar in the OKT3 and basiliximab groups, respectively. A minority of subjects in each group remained free from rejection (42% basiliximab vs 25% on OKT3, P  = NS). Renal function was superior in the basiliximab group (mean calculated creatinine clearance 79.4 ± 11.9 vs 54.5 ± 15.9 mL/min for  basiliximab vs OKT3, P  < 0.001). The incidence of major opportunistic infection was lower in basiliximab-treated patients (9 vs 50% in the OKT3 group, P  = 0.033). Basiliximab was associated with similar 6-month patient, kidney and pancreas survival, superior renal function and less opportunistic infection as compared with OKT3 induction therapy in SPK transplants. Basiliximab is at least as effective and is safer than OKT3 for induction therapy in SPK transplantation.     

BKV in Simultaneous Pancreas-Kidney Transplant Recipients: A Leading Cause of Renal Graft Loss in First 2 Years Post-Transplant

With the introduction of more potent immunosuppressive agents, rejection has decreased in simultaneous pancreas/kidney transplant (SPK) recipients. However, as a consequence, opportunistic infections have increased. The purpose of this report is to outline the course of SPK patients who developed polyomavirus-associated nephropathy (PVAN). A retrospective review of 146 consecutive SPK recipients from January 1, 1996 to December 31, 2002 was performed. Immunosuppression, rejection and development of PVAN were reviewed. Nine patients were identified. All received induction with either OKT3 or thymoglobulin. Immunosuppression included tacrolimus/cyclosporine, MMF/azathioprine and sirolimus/prednisone. Two patients were treated for kidney rejection prior to the diagnosis of PVAN. Time to diagnosis was an average of 359.3 days post-transplantation. Immunosuppression was decreased but five ultimately lost function. However, none developed pancreatic abnormalities as demonstrated by normal glucose and amylase. Two underwent renal retransplantation after PVAN diagnosis and both have normal kidney function. PVAN was the leading cause of renal loss in SPK patients in the first 2 years after transplantation and is a serious concern for SPK recipients. The pancreas, however, is spared from evidence of infection, and no pancreatic rejection occurred when immunosuppression was decreased.     

Steroid withdrawal in pancreas transplant recipients

BACKGROUND: Numerous studies of steroid withdrawal have been carried out in kidney and liver transplant recipients, but only a few in pancreas transplant recipients. Yet, pancreas transplant recipients could have significant long-term benefits from steroid withdrawal. METHODS: We performed a retrospective analysis to determine the feasibility of steroid withdrawal in pancreas transplant recipients. RESULTS: Of 360 recipients who underwent a pancreas transplant between January 1, 1994 and June 30, 1998, 14 attempted steroid withdrawal (12 simultaneous pancreas-kidney [SPK]; 2 pancreas transplant alone [PTA]). Reasons for steroid withdrawal were bone fractures (n = 3), psychiatric disorders (n = 2), severe acne (n = 1), recurrent infections (n = 4), and problems with hypercholesterolemia or hypertension (n = 4). All 14 were maintained on tacrolimus and mycophenolate mofetil (MMF) immunosuppression, except for 1 who was on tacrolimus and azathioprine (AZA). Of the 14 recipients, 11 had no episodes of acute rejection before steroid withdrawal. The remaining 3 had one or more acute rejection episodes. Of the 14 recipients, 10 (72%) currently remain off steroids (mean follow-up 18 months, range 5-51 months). However, 4 recipients have resumed steroids: 2 after an acute rejection episode (at 2 and 21 months post-withdrawal) and 2 because of leukopenia (WBC < 3000) and an inability to tolerate full-dose MMF. Steroid withdrawal was unsuccessful in both PTA recipients and in 2 of the 12 SPK recipients. All 14 recipients currently have a functioning pancreas graft. However, 1 of the SPK recipients, in whom steroid withdrawal failed, has developed chronic kidney rejection and is now back on hemodialysis awaiting a retransplant. CONCLUSION: Steroid withdrawal is possible in up to 70% of pancreas transplant recipients. Further studies are necessary to define ideal candidates for steroid withdrawal. Based on the results of this analysis, we have launched a prospective, randomized trial of steroid withdrawal in pancreas transplant recipients.     

Single-shot antithymocyte globulin (ATG) induction for pancreas/kidney transplantation: ATG-Fresenius versus Thymoglobulin

Single-shot antithymocyte globulin (ATG) prior to reperfusion followed by tacrolimus (TAC), mycophenolate mofetil (MMF), and prednisolone (PRD) is an established induction therapy in simultaneous pancreas kidney transplant (SPK) recipients. We retrospectively analyzed 6-month data from 105 patients who received their first SPK. From January 1996 to December 2000, ATG-Fresenius was used. Since January 2001, Thymoglobulin has been administered. In the first group, 58 patients were treated with ATG-Fresenius (4-6 mg/kg body weight). In the second group, 47 patients received Thymoglobulin (1.5-2.5 mg/kg body weight). HLA-mismatch was comparable. After an observation period of 6 months, patients, kidney, and pancreas graft survival is 98.3%, 96.6%, and 93.1% in group I and 97.9%, 97.9%, and 85.1% in group II, respectively. In each group, one death with functioning graft (DWFG) was observed. Twenty (34.5%) acute rejection episodes (AR) were observed (18 patients) in group I. They were treated with steroids (n = 16) or steroids/OKT3 (n = 4). One kidney graft failure was observed due to rejection and one due to DWFG. Four pancreas grafts were lost (thrombosis, n = 2; AR, n = 1; DWFG, n = 1). In group II, 15 AR (31.9%) were seen in 12 patients and were treated with steroids (n = 12), steroids/ATG (n = 1), or steroids/OKT3 (n = 2). Seven pancreas (thrombosis, n = 5; rejection, n = 1; DWFG, n = 1) and one kidney (DWFG, n = 1) graft losses occurred. These data clearly establish that single-shot ATG prior to reperfusion, followed by TAC, MMF, and PRD results in a low incidence of AR (34.5% in group I and 31.9% in group II) after SPK. Only 6.9% (group I) and 6.4% (group II) of the patients received antibodies for rejection treatment.     

A single center's clinical experience with quadruple immunosuppression including ATG or IL2 antibodies and mycophenolate mofetil in simultaneous pancreas–kidney transplants

Acute rejection remains a major problem in simultaneous pancreas–kidney (SPK) transplant and occurs in 60–100% of the cases.
With the introduction of mycophenolate mofetil (MMF) replacing azathioprine (AZA) as a basis immunosuppressant, reduced rates of rejection have been reported. This study investigates the frequency and clinical relevance of allograft rejection in SPK patients receiving anti‐thymocyte globulin (ATG) or Basiliximab® induction therapy and cyclosporine Neoral® (CyA), MMF, steroid basis immunosuppression.
Between December 1996 and October 1999, 21 consecutive patients (15 males, 6 females) received a SPK transplant at our institution with a mean±standard deviation (SD) age of 42±6 yr. Of these, 14 patients were treated with anti‐thymocyte globulin (ATG) Fresenius® (rabbit) 3–5 mg/kg for 6±2 d, cyclosporine Neoral (CyA) (trough levels 350–400 ng/mL), MMF 3 g/d and low dose steroid therapy. Seven SPK patients were treated with Basiliximab (Simulect®, Novartis 20 mg on d 0 and d 4 post‐transplant) instead of ATG. The patients had an average human leucocyte antigen (HLA) mismatch of 3.9/6 and a negative cross match. All patients remained on triple drug therapy. Three patients were switched to tacrolimus instead of Neoral for CyA intolerance. The mean±SD cold ischemia time (CIT) of the organs was 10.1±2.4 h for the pancreas and 10.5±2.6 h for the kidney.
Results: Biopsy‐proven rejection occurred in the kidney of 1 ATG patient (8%), which responded to steroid bolus therapy. One of the patients (14%) with Basiliximab induction developed renal allograft rejection, which was resolved after a 6‐d course of anti‐CD3 mAb (OKT3) treatment. All patients (100%) were free from rejection in the pancreas, as measured by urine amylase levels and glycemic control without the need for exogenous insulin with a mean glycosylated hemoglobin (HBA₁C) of 5.1±0.7% and serum creatinine with a mean of 1.24±0.24 mg/dL in a mean follow‐up period of 17±15 months (median 12, range 2–37).
Conclusion: Triple drug immunosuppression including cyclosporine, MMF and low dose steroids with ATG or interleukin 2 (IL2) receptor antibodies induction therapy appears to be a very suitable immunosuppressive regimen for combined pancreas–kidney transplant (PKT) with a marked reduction in the incidence of rejection.     

Thymoglobulin induction decreases rejection in solitary pancreas transplantation.

BACKGROUND: Solitary pancreas transplants, both pancreas transplant alone (PTA) and pancreas after kidney (PAK), have higher rejection rates and lower graft survivals than simultaneous pancreas-kidney transplants (SPK). The aim of this study is to compare three different antibody induction regimens in solitary pancreas transplant recipients and to assess the role of surveillance pancreas biopsies in the management of these patients. METHODS: Solitary pancreas transplant recipients between 01/98 to 02/00 (n=29) received induction with either daclizumab (1 mg/kg on day 0, 7, 14), OKT 3 (5 mg/day x0-7), or thymoglobulin (1.5 mg/kg/day x0-10). Maintenance immunosuppression was similar for the three groups. All rejections were biopsy-proven either by surveillance/protocol or when clinically indicated. RESULTS: The 1-year graft survival was 89.3% overall and 91.7% in the thymoglobulin group. Thymoglobulin significantly decreased rejection in the first 6 months when compared with OKT3 or daclizumab (7.7 vs. 60 vs. 50%). Acute rejections were seen on surveillance biopsies in the absence of biochemical abnormalities in 40% of patients. CONCLUSIONS: Thymoglobulin induction regimen led to a low incidence of acute rejection and a high rate of graft survival in solitary pancreas transplants. In addition, surveillance biopsies were useful in the detection of early acute rejection in the absence of biochemical abnormalities.