肝移植术后长期存活慢性肾功能损害受者的免疫抑制方案个体化应用

目的探讨肝移植术后长期存活慢性肾功能损害受者应用个体化免疫抑制方案的疗效。方法选择18岁以上、肝移植术后2年以上、入组前采用以他克莫司(FK506)为基础免疫抑制方案、肝功能正常而肾功能损害的受者,共32例。根据免疫功能评分和白细胞计数制定个体化免疫抑制方案,以FK06用量最小化为原则,转换为麦考酚吗乙酯(MMF)或西罗莫司,并调整其用量。调整后至少每个月随访1次,进行肝功能、肾功能、血常规检查和免疫功能评估。结果 32例受者经个体化免疫抑制方案治疗,随访(24.3±7.6)个月,个体化治疗后各时段的肾小球滤过率(GFR)均较此前有明显提高(均为P<0.01),以调整用药后1个月最明显。无发生排斥反应。结论根据免疫功能评分和白细胞计数制定个体化免疫方案,使FK506用量最小化,可以有效改善肝移植术后长期存活的受者的肾功能,并不增加排斥反应的发生率。     

肝移植术后早期急性肾功能衰竭5例临床分析

目的总结肝移植术后早期急性肾功能衰竭的防治经验。方法回顾性分析5例肝移植受者术后早期发生急性肾功能衰竭临床资料,手术方式为改良背驮式肝移植术,其中4例术前即合并肾功能不全。结果5例术后早期急性肾功能衰竭患者3例通过调整免疫抑制方案和改善肾脏灌注及利尿治疗肾功能恢复;2例给予连续性肾脏替代治疗后肾功能恢复。结论肝移植术后免疫抑制剂的个体化应用,积极改善肾脏灌注,必要时选择血液透析治疗,有助于防治肝移植术后早期急性肾功能衰竭。     

以西罗莫司为主的免疫抑制方案在肝癌肝移植受者中的应用

目的 探讨肝癌肝移植受者术后采用以西罗莫司联合两剂激素为主的免疫抑制方案的安全性和有效性.方法 2004年3月至2006年10月间,共为92例超出米兰标准的中晚期肝癌患者施行了肝移植.其中89例纳入研究.前54例患者采用以他克莫司为主的免疫抑制方案,后35例患者采用以西罗莫司为主的新免疫抑制方案.术后对两组受者均进行了随访.随访时检测受者的肝肾功能、血糖和血脂水平等生化指标,监测受者感染、急性排斥反应、肿瘤复发、存活率及药物副作用等表现,并对两组免疫抑制方案的效果进行了分析和比较.结果 两组间1年肿瘤复发率、3个月内感染发牛率、术后1个月高血糖发生率及术后1年肾功能损害和高脂血症发生率的比较,差异均有统计学意义(P<0.05);其它指标的比较,无显著性差异.结论 肝癌肝移植受者采用以西罗莫司联合两剂激素为主的免疫抑制方案是安全和有效的.该方案在有效抑制排斥反应的同时可显著降低受者的肿瘤复发率,还可减少感染发生率、高血糖及.肾功能损害,但增加了高脂血症发生率.     

肾功能受损的肝移植受者免疫抑制剂的调整方案

慢性肾功能衰竭在肝移植受者中相当常见.美国1990年至2000年间移植受者科学登记处(SRTR)的资料(共69 321例非肾器官移植受者)表明,肝移植后3年时,慢性肾功能衰竭的平均累积发生率为13.9％,5年时进一步增至18.1％.受者年龄、性别、移植前基础疾病(如丙型肝炎病毒感染)和肾功能状态以及免疫抑制剂等都是影响肝移植后慢性肾功能衰竭的危险因素.     

肝移植受者术前肝、肾功能对术后环孢素血药浓度的影响

目的 研究肝移植受者术前肝、肾功能状况对术后使用环孢素(CsA)血药浓度的影响.方法 选择2007年至2009年在中山大学附属第三医院行经典同种异体肝移植的65例受者,术后均采用含CsA的免疫抑制方案.按术前肝、肾功能生化检测指标分为两个亚组,其中肝、肾功能稍好组(Ⅰ组)37例,肝、肾功能稍差组(Ⅱ组)28例.采用荧光...     

国际肝移植协会中国专题会议概述(下)

二、免疫抑制剂的应用进展优化免疫抑制方案,改善移植受者的长期存活始终是临床医师关心的焦点.此次会议上多位专家就免疫抑制方案的优化进行了探讨.来自美国的John Fung教授对于目前临床上经常使用的免疫抑制剂和新的免疫抑制剂给出了综合性的评价.John Fung教授指出,他克莫司(Tac)仍然是肝移植术后免疫抑制方案的核心.通过对16项有关肝移植后初始采用Tac和环孢素A(CsA)的对照试验进行荟萃分析的结果显示,Tac组受者移植后1年的死亡率、移植物丢失率以及急性排斥反应发生率等均明显低于CsA组.     

肝移植术后受者并发急性左心功能衰竭的危险因素和预防措施

目的分析肝移植术后受者并发急性左心功能衰竭的危险因素，并总结其预防措施。方法回顾性分析230例肝移植受者的临床资料，其中16例术后发生急性左心功能衰竭。将受者分成左心功能衰竭组和心功能正常组，对22项肝移植术后并发急性左心功能衰竭的指标进行了单因素分析，采用Χ^2检验或t检验，将差异有统计学意义的因素纳入多因素模型进行Logistic回归分析，针对危险因素总结预防措施。结果单因素分析结果显示，心脏病史、肝功能分级、术中输血量、术后日平均液体平衡量及术后并发肾功能衰竭是发生急性左心功能衰竭的相关因素（P〈0．05）；多因素分析结果显示，肝功能分级、术中输血量、术后日平均液体平衡量及术后并发肾功能衰竭是急性左心功能衰竭的独立危险因素（P〈0．05）。结论肝移植术后受者并发急性左心功能衰竭是多种因素引起的；应在肝移植术前、术中及术后采取综合性预防措施。     

肝移植术后急性肾功能衰竭七例的防治

目的探讨同种异体原位肝移植术后急性肾功能衰竭的防治。方法回顾性分析5 1例肝移植的临床资料 ,总结肝移植术后急性肾功能衰竭的防治体会。结果 5 1例患者中 ,有 9例术前已存在不同程度的肾功能损害 (Cr≥ 132 μmol/L或BUN≥ 18μmol/L) ;其中 7例患者在术后 1周内并发了急性肾功能衰竭 ,术后选择了将赛尼哌加入常规的免疫抑制剂方案中作为免疫诱导 ,同时积极应用多巴胺等血管活性药物改善肾脏灌注 ;6例肾功能在 3～ 6d内得到纠正 ,1例患者经上述治疗效果欠佳 ,采用了无肝素血液透析 ,术后第 11天肾功能亦得到恢复。结论肝移植术后急性肾功能衰竭诱发因素众多 ;术后注意免疫抑制剂的个体化应用 ,积极改善肾脏灌注 ,必要时选择血液透析治疗 ,多数患者的肾功能能够得到恢复。     

肝移植术后西罗莫司替代钙调磷酸酶抑制剂的转换方案

目前,钙调磷酸酶抑制剂(CNI)是肝移植术后常用的主要免疫抑制剂.但其具有一定的肝肾毒性[1].因此,对于术后需长期服用CNI.特别是发生肾功能不全的肝移植受者,应密切监测受者的肝肾功能及合理渊整免疫抑制方案.2002年12月至2007年12月,我们对郎分肝移植术后出现肝肾功能不全的受者,采用以两罗莫司替代CNI的方案,以改善肝肾功能,效果良好.现报告如下.     

感染和免疫抑制剂相关神经毒性可能不是引起肝移植后中枢神经系统并发症的主要因素

中枢神经系统（central nervous system,CNS）并发症是肝移植后常见并发症,发生率达13％～47％,常由感染和免疫抑制剂的神经毒性引起。将肝移植受者免疫抑制方案从三联改为单用一种药物或者降低剂量可能有助于减少药物相关神经毒性,从而降低CNS并发症发生率。美国学者分析了1999-2008年单中心395例肝移植受者术后CNS并发症的发生率、临床表现、病因和结局。这些受者的术后免疫抑制方案采用维持较低血药浓度的他克莫司。该研究纳入的CNS主要临床表现包括持续的精神状态改变、神经系统局灶征、严重的头痛和癫痫。     

个体化免疫抑制治疗在肾移植的疗效观察

目的：探讨个体化免疫抑制治疗对肾移植患者的临床价值。方法：将肾移植患者分为个体化组(42例)和常规组(50例),分别采用个体化免疫抑制治疗和常规免疫抑制治疗,并对术后两组的临床指标进行比较。结果：个体化组比较常规组,术后肝功能损害、高血糖、胃肠功能紊乱、呼吸系统感染、急性排斥反应发生率均明显降低(P＜0．05);而巨细胞病毒感染发生率及移植肾切除人数无差异(P＞0．05)。结论：个体化免疫抑制治疗既能维持免疫抑制效果,又能最大限度减少药物不良反应,对肾移植患者有较好治疗价值。     

Infections in organ transplantations

Since cyclosporin A was introduced clinically, transplantation of solid organ grafts, has become a routine therapy for untreatable endstage-diseases of various organs, such as kidney, liver, heart and lung. Nowadays the most frequent cause of mortality and severe morbidity in transplant recipients is not graft rejection but infection. During the first three postoperative months organ recipients are extremely endangered for infectious diseases. Patients receive high dosages of immunosuppressive therapy, because immunogenecity of the graft is rather high. In course of the following months the allograft is more and more accepted by the recipients immune system. Consecutively immunosuppression is reduced and the risk of infection is diminished. --During the first postoperative month bacterial infections commonly appear. Thereafter viral infections can be observed more frequently. Cytomegalovirus infections are very dangerous in CMV-seronegative recipients with a lethality up to 90%. So a CMV-cross-match between the donor and recipient has to be performed. Transplant recipients have to be operated in aseptic conditions, with perioperative antibiotic prophylaxis. Regular serological analysis from blood and urine specimen has to be done to control bacterial, fungal and viral status, as well as regular monitoring of immunosuppressive regimen.     

两剂激素联合两剂达利珠单抗及他克莫司的免疫抑制方案在肝移植中的应用

目的 探讨两剂激素联合两剂达利珠单抗及他克莫司(FK506)的免疫抑制方案在肝移植中应用的安全性及有效性.方法 中山大学附属第一医院器官移植中心2006年9月至2008年3月共实施成人肝移植74例,排除3例血型不合、4例围手术期死亡外,余67例纳人本研究,其中男性54例,女性13例,年龄28～66岁,平均(46.9±8.7)岁.将67例成人肝移植患者随机分为两组:传统免疫抑制方案(激素3个月撤离)组(n=35)和两剂激素免疫抑制方案组(n=32),比较两组术后代谢并发症、感染(含细菌、真菌及巨细胞病毒感染)及排斥反应的发生率的差异.结果 两组患者的术后早期高血糖发生率,高血糖患者使用胰岛素的平均剂量,随访期内糖尿病、高血压及感染的发生率的差异有统计学意义(P<0.05);术后早期高血压发生率及随访期内排斥反应的发生率和高脂血症发生率无明显差异(P0.05).结论 两剂激素的免疫抑制方案是安全有效的,其不增加急性排斥反应的发生率,并可显著减少长期使用激素引起的各种不良反应及并发症的发生.     

肝移植术后真菌感染患者免疫抑制方案的调整

目的 探讨肝移植术后真菌感染患者的免疫抑制方案。方法 我院器官移植中心从2004年1月至2005年12月实施376例成人肝移植，对术前、术中存在真菌感染危险冈素的59例患者采用IL-2（interleukin-2）受体单克隆抗体诱导方案，对术后发生真菌感染的患者在应用有效抗真菌药物的同时，调整其免疫抑制方案。结果 共有36例患者发生真菌感染，发生真菌感染的中位时间为术后19d（4～75d），其中无临床症状仅真菌培养阳性16例，20例患者出现临床感染症状，感染部位以呼吸道（11/20，55%）为主，4例患者死于严重感染。真菌菌株培养多为白色念珠菌（24/41，58.5%）。16例患者减少免疫抑制剂，20例有临床表现的患者停用免疫抑制剂，减药或停药过程中仅1例患者出现排斥反应。结论 真菌感染是肝移植术后的重要并发症，术前或术中存在真菌易感因素患者应采用IL-2受体单克隆抗体诱导方案，术后发生真菌感染的患者在应用有效抗真菌药物同时，应减少或停用免疫抑制药物。     

Infection-related mortality in a large cohort of renal transplant recipients

INTRODUCTION: Infections represent a major cause of morbidity and mortality among renal transplant recipients. Our aim was to analyze the incidence and etiology of infection-related mortality among a large cohort of renal transplant recipients. METHODS: From 1995 to 2004, we collected all causes of mortality among patients receiving a renal transplantation. The date of transplant, the last follow-up/death, type of transplant, age, and cause of death were tabulated into a database. The incidence rate of mortality was calculated in events per 10,000 transplant months. RESULTS: Among the 1218 renal transplants performed in the study period the causes of mortality were: cardiovascular, 65 (38%); infection, 49 (29%); cancer, 21 (12%); other causes, 18 (10.5%); and unknown, 18 (10.5%). Infection-related mortality were: sepsis = 17 (35%), bacterial pneumonia = 9 (18%), abdominal bacterial infection = 2 (4%), invasive viral infection = 12 (24%), and invasive fungal infection = 9 (18%). There were no differences in the global causes of mortality according to the year of transplantation. The incidence rate of infection-related mortality was higher among aged patients and similar to cardiovascular-related mortality. Comparing the periods 1995 to 1999 with 2000 to 2004, bacterial infection-related mortality remained stable (57% vs 57%), while viral infection-related mortality decreased (31% vs 7%) and fungal infection-related mortality increased (11% vs 36%; P = .06). CONCLUSIONS: In the last decade, infection-related mortality among renal transplant recipients has not decreased. Although better control of invasive viral infections has been achieved, bacterial and fungal invasive infections remain important causes of mortality in this population.     

高危患者肾移植长期存活的临床经验

目的 总结高危肾移植的临床经验,寻找提高长期存活率的方法.方法 将1991年4月至2008年12月我院治疗的921例高危.肾移植病例分为儿童组(34例)、再次移植(再植)组(169例)、高敏组(35例)、高龄组(297例)、糖尿病组(112例)和肝炎病毒感染或携带(肝炎)组(274例),并以807例普通肾移植受者作为对照组,对受者和移植.肾(人/肾)存活率、急性和慢性排斥反应(AR/CR)以及并发症的发生率进行回顾性分析.结果 再植组、高敏组以及肝炎组人/肾存活率均低于对照组(P＜0.05);高龄组仅患者生存率低于对照组(P＜0.05).同对照组相比,儿童组和高敏组等免疫性高危受者AR/CR发生率高(P＜0.05);高龄组、精尿病组以及肝炎组等非免疫性高危受者并发症的种类多,且发病率高.结论 减少AR发生,有利于提高免疫性高危患者的长期存活率;降低并发症发生率,有利于提高非免疫性高危患者的长期存活率.     

Death after rejection with severe hemodynamic compromise in pediatric heart transplant recipients: a multi-institutional study.

BACKGROUND: Rejection with severe hemodynamic compromise results in high mortality in adult transplant patients. This study determines the incidence, outcome and risk factors for rejection with severe hemodynamic compromise in a multi-institutional study of pediatric heart transplant recipients. METHODS: Data from 847 patients transplanted between 1/1/93 and 12/31/98 at 18 centers in the Pediatric Heart Transplant Study were analyzed. Rejection with severe hemodynamic compromise was defined as a clinical event occurring beyond 1 week postoperatively, which led to augmentation of immunosuppression and use of inotropic therapy. Actuarial freedom from such rejection and death after rejection were determined and risk factors sought. RESULTS: Among 1,033 rejection episodes in 532 patients, 113 (11%) episodes were associated with severe hemodynamic compromise in 95 patients. The highest risk for severe rejection was in the first year. Risk factors were older recipient age (p >.05) and non-white race (p >.001). Survival after an episode was poor (60%), and biopsy score did not affect outcome. Deaths were due to rejection (n = 14), other cardiac causes (n = 17), infection (n = 5), lymphoma (n = 2), pulmonary causes (n = 2), and thrombosis (n = 1). CONCLUSIONS: Rejection with severe hemodynamic compromise occurs in 11% of pediatric patients, irrespective of age, sex or biopsy score, and mortality is high. Non-white race and older recipient age are independent risk factors for rejection with severe hemodynamic compromise. Aggressive treatment and close surveillance should be crucial components of protocols aimed at reducing the high mortality.     

Fungal Infection in Heart Transplant Recipients With Severe Sepsis: Single-Center Experience

The objective of this study was to describe in heart transplant recipients severe sepsis due to fungal infection, which is associated with high mortality. This was a retrospective study including 366 patients who underwent heart transplantation from 1987 to 2009 in whom severe sepsis due to fungal infection developed, with multiple-organ failure. Sepsis was diagnosed on the basis of a positive culture for the infective agent, such as Cryptococcus, Aspergillus, Candida, or Nocardia, from an appropriate source such as blood, wound, or sputum. In 10 patients, severe sepsis due to fungal infection was treated temporally by reducing or sparing immunosuppression; 7 of these patients survived after intensive care. Only 1 patient required pulsed therapy because of an acute rejection episode. Early diagnosis with aggressive diagnostic techniques and use of combination therapy must be considered to reduce the risk of death in heart transplant recipients with fungal infection.     

Preoperative risk factor assessment in liver transplantation.

BACKGROUND. Despite the increasing success of liver transplantation, there is lack of objective data defining appropriate candidate suitability. This study was undertaken to determine preoperative risk factors that independently or in combination affected outcome after orthotopic liver transplantation. METHODS. We reviewed data on 229 consecutive adult liver transplant recipients. Thirty-one preoperative risk factors recorded at the time of listing and immediately before transplantation were analyzed. Outcome variables included hospital mortality rates, bacterial or fungal sepsis, and the need for renal support. RESULTS. The overall hospital mortality rate was 15.7%. Patients who were in the intensive care unit immediately before transplantation had the highest hospital mortality rate (32.6%; p = 0.006), incidence of bacterial sepsis (51%; p = 0.001), fungal infection rate (27.6%; p = 0.001), and need for renal support (38.7%; p = 0.001). Preoperative renal dysfunction was significantly associated with sepsis and was reflected in higher hospital mortality rates (29.5%; p = 0.011). Child-Pugh class C was associated with higher mortality rates (23.9%; p = 0.017), an increased incidence of bacterial (37.2%; p = 0.020) and fungal infection (20.3%; p = 0.049), and a 30.4% requirement for postoperative renal support (p = 0.004). CONCLUSIONS. These results emphasize the need for earlier referral and transplantation in patients with advanced liver disease. Further studies are needed to refine identified risk profiles and devise strategies to decrease morbidity and mortality rates.     

African-American renal transplant recipients experience decreased risk of death due to infection: possible implications for immunosuppressive strategies

INTRODUCTION: African-American renal transplant recipients tend to experience more acute rejection episodes and have shorter graft survival than Caucasian renal transplant recipients. Various factors have been posited to be responsible for this difference, including relative under immunosuppression. We reasoned that by looking at the balance of acute rejections versus death due to infection, we could ascertain whether African-American renal recipients might have more reserve to tolerate an increase in pharmacological immunosuppression. METHODS: We analyzed the United States Renal Data System (USRDS) data from 1987 to 1997 regarding acute rejection episodes and infectious deaths. All other pertinent factors were gathered for a multivariate analysis. A total number of 68,885 adult renal transplant recipients were analyzed. RESULTS: When corrected for all covariates, the relative risk for acute rejection (1.3) was higher although the relative risk for infectious death was lower (0.7) in African-Americans as compared with Caucasians (P<0.01). CONCLUSION: Our study would indicate that relative to Caucasians, African-American renal transplant recipients are at decreased risk for infectious death and therefore may tolerate the more intensive immunosuppression that may be necessary to narrow the gap in acute rejection rates between African-Americans and Caucasian renal transplant recipients.