他克莫司在移植肾功能延迟恢复患者中的临床应用

目的:探讨他克莫司(FK506)在移植肾功能延迟恢复(DGF)患者中的临床应用价值与合理用药方案.方法:17例DGF患者临床结合移植肾病理确立诊断.肾移植术后早期均接受三联(FK506 MMF Pred)免疫抑制药物治疗至少3个月.不用任何生物制剂诱导治疗,观察临床疗效及副作用.结果:17例患者无一例死亡或摘除移植肾.15例在术后第2～3天开始血液透析(HD)/连续性血液净化(CBP)治疗,2例在术后第5天开始HD/CBP.HD/CBP治疗2～15次后,10例在术后7天内停止,7例在术后7天后仍需CBP治疗,最长1例在术后第18天停止透析.FK506治疗后8～17天患者尿量开始明显增多,SCr开始明显下降.17例患者诊断DGF时SCr水平在489～1028μmol/L,14例在治疗后8～17天降至＜200μmol/L,另3例中2例SCr分别在术后第24天,28天降至＜200μmol/L.副作用主要是腹泻(3例),血糖升高(1例)及手颤,肢体麻木(4例),但未出现CMV等严重感染病例.结论:FK506 MMF Pred三联免疫抑制治疗方案治疗肾移植DGF安全有效,可作为肾移植术后DGF患者的过渡治疗方法之一.     

老年患者肾移植术后他克莫司应用体会

老年患者肾移植以往采用环孢素治疗，但其影响老年血脂代谢，而新型免疫抑制药他克莫司对血脂代谢影响甚微。我院2000年9月应用他克莫司，本文对比观察老年和成年患者他克莫司用药情况。     

他克莫司治疗移植肾慢性排斥的初步临床观察

目的：探讨他克莫司（FK506）、环孢素A（CsA)治疗移植肾慢性排斥（CR)的可行性及安全性。方法：40例同种异体肾移植患者肾功能减退经病理证实为CR，随机分为CsA切我为FK506组20例、继续使用CsA组20例。观察各组移植肾功能、肾小球滤过率、蛋白尿、血压、血脂变化及急性排斥（AR）发生率，治疗后随访12个月。结果：追踪12个月，FK506组16例移植肾功能稳定（80％）；3例行血液透析治疗，1例死亡，人存活率95％。CsA组15例移植肾功能稳定，3例行血液透析治疗，逆转成功率75％；2例死亡，人存活率90％。结论：FK506可以延缓慢性移植物失功。FK506的使用是安全和有效的。     

他克莫司致反复急性肾衰竭1例

<正>患者男,31岁。因同胞HLA全相合异基因外周血造血干细胞移植术后3月余,食欲下降1周,于2014年4月1日入院。患者于2013年8月确诊为慢性粒细胞白血病慢性期,口服伊马替尼治疗3个月,复查血常规正常,骨髓细胞学完全缓解,但BCRABL融合基因p210阳性,Ph染色体阳性,患者与其胞妹HLA配型6/6相合,于2014年1月行异基因     

他克莫司致肥厚型心肌病1例

患者 ,女 ,48岁。 8年前因慢性肾动脉衰竭行肾移植术 ,术后口服抗排异药物 (包括骁悉、新山的明及泼尼松 )。 3个月前因出现肾功能不全 ,停用新山的明 ,改服他克莫司 (商品名 :高科复 ) 1mg/d ,半个月前增量致 2mg/d。 1周前出现胸痛 ,活动后明显加重 ,每次持续 2～ 3min ,休息后缓解 ,无晕厥史 ,拟诊为冠心病收治入院。既往有高血压史 ,血压最高达 2 2 0 /1 2 0mmHg( 1mmHg=0 .1 33kPa) ,肾移植术后血压控制在 1 5 0 /90mmHg以下。否认糖尿病史 ,已停经 1年。体检 :血压 1 2 0 /70mmHg ,心率 70次 /min ,律齐。胸骨左缘 3～ 4肋间可闻及 …     

他克莫司引起急性造血功能停滞2例

他克莫司(tacrolims，FK506)是一种新型的免疫抑制剂，已被广泛应用于器官移植。FK506的副作用与环苞菌素A(CsA)是相似的，包括肾毒性。然而FK506对造血系统的副作用还没见详细报道。我们近来观察到2例器官移植后应用FK506出现急性造血功能停滞的病例，现报告如下。     

CYP3A5基因多态性检测对肝移植患者术后他克莫司用药的指导作用

目的探讨CYP3A5基因多态性检测对肝移植患者术后他克莫司（FKS06）用药的指导作用。方法选择接受原位肝移植术的患者67例,采用DNA直接测序法检测患者CYP3A5基因多态性,计算肝移植术后1周、2周、1个月患者每千克体质量每天的FKS06剂量（D）,采用ELISA法检测各时点全血FKS06谷浓度,计算浓度／剂量比值（C／D）。结果67例肝移植患者中,CYP3A5％＊／＊1基因型15例（22．4％）,CYP3A5＊1／＊3基因型23例（34．3％）,CYP3A5＊3／＊3基因型29例（43．3％）。CYP3A5＊3／＊3基因型肝移植患者术后1周、2周、1个月FK506的C／D值显著高于CYP3A5＊1／＊1、CYP3A5＊1／＊3基因型（P均〈0．05）。结论CYP3A5＊3／＊3基因型较CYP3A5＊1／＊1、CYP3A5＊1／＊3基因型肝移植患者术后应用FKS06达到血药浓度所需剂量更低,检测患者CYP3A5基因多态性有助于肝移植术后FKS06的个性化治疗。     

基因多态性与他克莫司的慢性肾毒性

以他克莫司为代表的神经钙蛋白抑制剂是实体器官移植免疫抑制方案的重要组成部分,被广泛应用于临床.他克莫司治疗窗狭窄,药物浓度个体差异大,因此,肾毒性是其主要的药物不良反应之一.多种基因参与他克莫司的药代动力学和药效动力学过程,但这些基因的多态性是否与他克莫司慢性肾毒性相关至今尚无定论.本文就这方面的研究做一综述.     

他克莫司治疗Alport综合征的近期疗效

目的:观察他克莫司(tacrolimus,FK506)治疗Alport综合征(Alport syndrome,AS)的近期疗效.方法:前瞻性观察5例接受FK506治疗的AS患者的近期临床疗效与不良反应.5例患者均经肾活检确诊,男4例,女1例,年龄8～42岁,其中X连锁遗传患者4例,常染色体隐性遗传患者1例.起始FK506治疗剂量为0.15mg/(kg·d),8周后减至0.1 mg/(kg·d),目标血药浓度5～8 ng/dl.随访中每2～4周监测一次FK506的不良反应.4例患者行CYP3A5基因型检测,一例基因型为CYP3A5-* 1/* 1的患者FK506谷浓度始终未达到目标范围.结果:治疗2～4周5例患者蛋白尿明显减少,血清白蛋白升高,但随治疗时间延长,蛋白尿未进一步减少,甚至再次增多.2例延长治疗时间至36周和40周,血清白蛋白维持在33～35g/L,尿蛋白波动于0.5～2.5g/L.2例出现肾毒性和(或)糖代谢异常,FK506减量后不良反应消失,1例未达到目标血药浓度者治疗无效.结论:小样本临床观察显示短期FK506治疗能改善AS患者的蛋白尿及低白蛋白血症,其长期疗效有待进一步观察.     

他克莫司防治移植肾急性排斥反应的临床研究

目的 :研究他克莫司 (Tacrolimus ,Prograf,FK5 0 6 )在肾移植术后抗排斥反应的效果及毒副作用。　方法 :2 94例肾移植受者术后服用FK5 0 6。其中 2 6 8例在术后 2 4h即开始服用FK5 0 6 ,起始量 0 15mg/ (kg·d) ;2 6例应用环孢素A(CsA)的患者在术后 7～ 14天内出现排斥反应 ,经甲基强的松龙 (MP)冲击治疗无效后改用FK5 0 6治疗。观察FK5 0 6的治疗效果、理想的治疗窗及毒副作用。　 结果 :连续使用FK5 0 6的 2 6 8例患者中 ,肾功能 2～ 7天恢复正常者 198例 ,8～ 15天恢复正常者 4 4例 ,16～ 2 0天恢复正常者 2 1例 ,肾功能未恢复正常者 5例。发生急性排斥反应 (AR) 10 5 % (2 8/ 2 6 8) ,糖代谢紊乱 9 33% (2 5 / 2 6 8) ,神经系统功能紊乱 1 4 9% (4 / 2 6 8) ,肝功能异常 2 99%(8/ 2 6 8) ,肾中毒 1 87% (5 / 2 6 8) ,消化功能紊乱 17 5 % (4 7/ 2 6 8) ,巨细胞病毒 (CMV)血症 2 99% (8/ 2 6 8) ,肺部非CMV感染 1 4 9% (4 / 2 6 8)。脑出血死亡 0 37% (1/ 2 6 8) ,移植肾功能丧失、摘除移植肾 1 12 % (3/ 2 6 8)。FK5 0 6血药浓度为5～ 2 0 μg/L。 2 6例由CsA切换FK5 0 6治疗的耐激素性排斥反应患者中 ,有 2 3例肾功能 8～ 15天恢复正常 ,治愈率88 4 6 % (2 3/ 2 6 ) ,3例 2 8～ 32天肾功能恢     

Tacrolimus dosage requirements in living donor liver transplant recipients with small-for-size grafts

AIM： To investigate the tacrolimus dosage requirements and blood concentrations in adult-to-adult right lobe living donor liver transplantation （AALDLT） recipients with small-for-size （SFS） grafts. METHODS： During January 2007 and October 2008, a total of 54 cases of AALDLT with an observation period of 6 mo were enrolled in this study. The 54 patients were divided into two groups according to graftrecipient body weight ratio （GRBW）： SFS grafts group （Group S, GRBW 〈 0.8%, n = 8） and non-SFS grafts group （Group N, GRBW ≥ 0.8%, n = 46）. Tacrolimus 12-hour blood levels and doses were recorded during weeks 1, 2, 3 and 4 and months 2, 3, 4, 5 and 6 in group S and group N. Meanwhile, acute rejection rates, liver and renal function test results, and the number of potentially interacting medications were determined at each interval in the two groups. A comparison of tacrolimus dosage requirements and blood levels were made weekly in the first month post-surgery, and monthly from months 2 to 6. RESULTS： There were no differences in the demo-graphic characteristics, acute rejection rates, liver and renal function test results, or the number of potentially interacting medications administered between the two groups. The tacrolimus dosage requirements in group S were significantly lower than group N at 2 wk （2.8 ± 0.4 mg/d vs 3.6 ± 0.7 mg/d, P = 0.006）, 3 wk （2.9± 0.7 mg/d vs 3.9±0.8 rag/d, P = 0.008）, 4 wk （2.9 ± 0.8 mg/d vs 3.9 ± 1.0 mg/d, P = 0.023） and 2 mo （2.8 ±0.7 mg/d vs 3.8±1.1 mg/d, P = 0.033）. Tacrolimus 12-h trough concentrations were similar between the two groups at all times except for 2 wk post-transplantation, when the concentrations were significantly greater in group S recipients than in group N recipients （11.3 ± 4.8 ng/mL vs 7.0 ± 3.8 ng/mL, P = 0.026）. CONCLUSION： SFS grafts recipients have significantly decreased tacrolimus dosage requirements compared with non-SFS grafts recipients in AALDLT during the first 2 mo post-surgery.     

Hyperhomocysteinaemia in heart transplant recipients

The aim of this study was to determine the prevalence of hyperhomocysteinaemiain cardiac transplant recipients, Three groups of subjects werestudied: 27 heart transplant recipients, 14 to 63 months (mean=36.5)after transplantation; 10 patients with moderate chronic renalinsufficiency without clinical evidence of vascular disease;17 apparently healthy individuals. Twenty-five out of 27 transplantedpatients had a coronaroangiography within 6 months of homocysteinemeasurement. Plasma homocysteine was measured both while thesubject was fasting (tO) and 6 h after administration of 0.1g. kg^–1 of methionine (t6). Hyperhomocysteinaemia waspresent in 14127 fasting transplanted patients and after methionineloading. Mean plasma levels of homocysteine at tO were higher(P=0.03) in transplanted heart recipients (15.4 ± 7µmol.l^–1 than in the renal patients (9.9±5µmol.l^–1) despite similar mean plasma creatinin. In eight transplantedpatients with angiographic coronary abnormalities of the cardiacgraft, homocysteinaemia was at tO 17.1 ±9 µmol.l^–1 and at t6 47.8 ±25 µmol. l^–1. In17 transplanted patients with angiographically normal coronaryarteries, plasma homocysteine levels were at tO, 13.2 ±4µmol.l^–1 and at t6, 46.8±25µmol. l^–1. We conclude that hyperhomocysteinaemia is common in transplantedheart recipients, and partly related to renal insufficiency.No correlation was found between hyperhomocysteinaemia and angiographicevidence of coronary atherosclerosis of the graft, but the populationof the study was possibly too small to establish this correlation.     

Long term results of heart transplantation in patients with amyloid heart disease

OBJECTIVE—To determine the outcome of heart transplantation for end stage amyloid heart disease in patients treated at a single centre.
DESIGN—Records of all patients with amyloid heart disease who underwent heart transplantation were examined to determine survival, graft involvement by amyloid, the course of systemic amyloid disease, and the cause of death.
PATIENTS—10 patients, mean (SD) age 54 (8) years, received transplants in the 13 year period 1984 to 1997.
RESULTS—Two patients, both with AL amyloid (primary systemic amyloidosis), died perioperatively. Mean follow up in the remaining eight patients was 49.9 (39.5) months (range 3-116 months). Amyloid deposits in the grafts became evident histologically in five patients with AL amyloid at 5, 11, 12, 28, and 30 months after transplantation, and in one patient with familial amyloid at 60 months. Echocardiography showed no evidence of left ventricular systolic impairment at the time of recurrence. Seven patients died, at 3, 11, 26, 32, 49, 85, and 116 months after transplantation; four of these deaths were related to amyloidosis. Actuarial survival at one and two years was 60% and at five years, 30%.
CONCLUSIONS—Heart transplantation for amyloid heart disease remains controversial because of the scarcity of hearts for transplantation, the systemic nature of amyloidosis, and the potential for amyloid deposition in the graft. Postoperative mortality was high (20%), reflecting extracardiac amyloid. Heart transplantation for end stage cardiac amyloidosis is feasible but, without treatment of the underlying process, it is a palliative procedure.


Keywords: heart transplantation; amyloid heart disease; heart failure     

Indications for heart transplantation in congenital heart disease

In this review we have looked at indications for cardiac transplantation in congenital heart disease. An outline of the general principles of the use of transplant as a management strategy both as a first line treatment and following other surgical interventions is discussed. We explore the importance of the timing of patient referral and the evaluations undertaken, and how the results of these may vary between patients with congenital heart disease and patients with other causes of end-stage heart failure. The potential complications associated with patients with congenital heart disease need to be both anticipated and managed appropriately by an experienced team. Timing of transplantation in congenital heart disease is difficult to standardize as the group of patients is heterogeneous. We discuss the role and limitations of investigations such as BNP, 6 minute walk, metabolic exercise testing and self estimated physical functioning. We also discuss the suitability for listing. It is clear that congenital heart patients should not be considered to be at uniform high risk of death at transplant. Morbidity varies greatly in the congenital patient population with the failing Fontan circulation having a far higher risk than a failing Mustard circulation. However the underlying issue of imbalance between donor organ supply and demand needs to be addressed as transplant teams are finding themselves in the increasingly difficult situation of supporting growing numbers of patients with a diverse range of pathologies with declining numbers of donor organs.     

Impact of pulmonary vascular resistances in heart transplantation for congenital heart disease

Congenital heart disease is one of the major diagnoses in pediatric heart transplantation recipients of all age groups. Assessment of pulmonary vascular resistance in these patients prior to transplantation is crucial to determine their candidacy, however, it is frequently inaccurate because of their abnormal anatomy and physiology. This problem places them at significant risk for pulmonary hypertension and right ventricular failure post transplantation. The pathophysiology of pulmonary vascular disease in children with congenital heart disease depends on their pulmonary blood flow patterns, systemic ventricle function, as well as semilunar valves and atrioventricular valves structure and function. In our review we analyze the pathophysiology of pulmonary vascular disease in children with congenital heart disease and end-stage heart failure, and outline the state of the art pre-transplantation medical and surgical management to achieve reverse remodeling of the pulmonary vasculature by using pulmonary vasodilators and mechanical circulatory support.     

Predicting the occurrence of diabetes mellitus in recipients of heart transplants.

AIMS: To establish the incidence of post-transplant diabetes mellitus (PTDM) and factors predictive of its development. METHODS: This was a retrospective review (using hospital records and transplant database) of 97 consecutive adult patients who underwent cardiac transplantation at St Vincent's Hospital, Sydney, Australia. RESULTS: Mean follow-up was 27 months. Excluding five patients who had pre-existing diabetes, the cumulative incidence of PTDM was 15.7%. Pre-transplant random blood glucose (5.6 +/- 0.8 vs. 5.2 +/- 0.6 mmol/l, P<0.05), family history (46% vs. 15%, P<0.05) and a continuing requirement for insulin on the second post-transplant day (54% vs. 15%, P< 0.01) differed in those who developed PTDM as opposed to those who remained free of diabetes. Patients who developed PTDM had received slightly higher mean doses of prednisolone at three months (0.21 +/- 0.03 vs. 0.19 +/- 0.03 mg. kg(-1)/day(-1), P<0.01). Of the factors identifiable prior to initial hospital discharge, only family history of diabetes mellitus and second post-transplant day insulin requirement independently predicted the occurrence of PTDM. CONCLUSIONS: A family history of diabetes and the need for insulin beyond the first 24 h after transplantation are factors identifiable prior to hospital discharge, which predict patients at risk of developing PTDM. In such patients, consideration to minimizing the dose of glucocorticoids should be given where possible.     

37例心脏移植的体外循环管理经验

目的:总结37例原位心脏移植体外循环管理经验。方法:37名患者进行了同种异体心脏移植手术,术前心脏超声检查EF值平均(24.52±4.79)%;采用中度低温、轻中度血液稀释、中高流量体外循环灌注。术中监测血气和电解质,常规使用超滤技术和白蛋白。供心保护采用HTK心肌保护液,经主动脉根部灌注冷HTK心脏停搏液,快速取下心脏,并放置于冷HTK液中低温保存。结果:供心热缺血时间(7.7±1.7)min,冷缺血时间(194.52±121.57)min,体外循环时间(110.87±29.83)min。主动脉阻断时间为(47.83±8.91)min,平均动脉压55～85mmHg。37例患者均顺利脱离体外循环机。结论:良好的供心保护,体外循环过程中保持平均动脉压在60～80mmHg及晶胶比在0.45～0.60,血气和电解质的动态监测以及超滤和白蛋白的应用是心脏移植体外循环管理的关键。     

Home inotrope treatment for intractable heart failure following heart transplantation

A 49 year old man developed intractable heart failure three years after undergoing heart transplantation. Coronary angiography showed no evidence of graft vascular disease. An initial cardiac biopsy identified one episode of rejection which responded to augmented immunosuppressive treatment. The patient became inotrope dependent and has now survived at home for 22 months using an ambulatory delivery system for intravenous adrenaline (epinephrine), without significant complications. There has been a noticeable improvement in symptoms and left ventricular systolic performance, both clinically and as seen through echocardiographic and radiographic examination. This improvement was substantiated by the results of cardiac catheterisation, which showed a return to normal left ventricular filling pressure and cardiac output. The case is noteworthy because this treatment has allowed a patient who otherwise would have been hospital bound to return to the community. With the current shortage of organs, he would have been unlikely to receive a second transplant. The clinical features and outcome, and social, medicolegal, and financial issues are discussed.     

Pediatric heart transplantation

Pediatric heart transplantation (pHTx) represents a small (14%) but very important and particular part in the field of cardiac transplantation. This treatment has lifelong impact on children. To achieve the best short and especially long-term survival with adequate quality of life, which is of crucial importance for this young patient population, one has to realize and understand the differences with adult HTx. Indication for transplantation, waitlist management including ABO incompatible (ABOi) transplantation and immunosuppression differ. Although young transplant recipients are ultimately likely to be considered for re-transplantation. One has to distinguish between myopathy and complex congenital heart disease (CHD). The differences in anatomy and physiology make the surgical procedure much more complex and create unique challenges. These recipients need a well-organized and educated team with pediatric cardiologists and intensivists, including a high skilled surgeon, which is dedicated to pHTx. Therefore, these types of transplants are best concentrated in specialized centers to achieve promising outcome.     

尸肾移植术后免疫抑制剂Sandimmun和Neoral药物动力学参数比较及临床应用研究

Ｎｅｏｒａｌ胶囊是继Ｓａｎｄｉｍｍｕｎ口服液后的另一种剂型。本文研究二者药物动力学参数及临床应用结果。第一部分选择５例肾移植术后超过３个月的稳定患者作自身对照。改用剂型按照１：１的转换剂量，改用前和口服Ｎｅｏｒａｌ８天后，每小时分别测二种剂型血ＣｓＡ浓度，连续测１２ｈ．第二部分对１２例尸肾移植术后分两组，分别口服二种剂型ＣｓＡ，长达１２周，同法测血ＣｓＡ浓度，求出药物动力学参数，加上临床观察。结论：①Ｎｅｏ－ｒａｌ胶囊比Ｓａｎｄｉｍｍｕｎ口服液吸收好，而且稳定。相对生物利用度比Ｓａｎｄｉｍｍｕｎ口服液高２７．５％；②Ｎｅｏｒａｌ胶囊达峰时间比Ｓａｎｄｉｍｍｕｎ口服液短和达峰浓度高，ＡＵＣ也比Ｓａｎｄｉｍｍｕｎ口服液大；③Ｎｅｏｒａｌ胶囊的谷浓度和其ＡＵＣ相关性好，用谷浓度估计ＡＵＣ和调整临床用药量，可靠性大。