肝肾联合移植36例的预后分析

目的 分析肝肾联合移植36例的治疗效果及存活情况.方法 回顾性分析20022011年单中心施行的36例肝肾联合移植的临床资料.受者的年龄为(47.4±13.1)岁,术前4例曾接受过肝移植,7例曾接受肾移植.统计术后并发症发生情况及受者和移植物的存活情况.结果 存活受者随访47.9个月(29.1～115.7个月).术后1、3和5年受者存活率分别为88.7％、85.4％和81.4％;1、3和5年移植肝存活率分别为79.8％、76.3％和72.3％;1、3和5年移植肾存活率分别为85.7％、82.4％和78.2％.3例受者因严重胆道并发症进行了再次肝移植,1例受者因移植肾功能丧失进行了再次肾移植.结论 肝肾联合移植是治疗终末期肝病伴肾功能衰竭的有效方法,受者和移植物可获得良好的预后.     

肝肾联合移植的临床经验

目的 探讨肝肾联合移植的适应证、手术技术、治疗经验及并发症防治。方法2001年10月至2005年3月进行肝肾联合移植13例。男12例，女1例。年龄41—66岁，平均54岁。原发病：多囊肝、多囊肾并尿毒症3例，酒精性肝硬化合并尿毒症2例，乙型肝炎肝硬化合并尿毒症7例，肾移植术后14年丙型肝炎肝硬化导致肝衰竭伴移植肾功能不全尿毒症1例。肝移植采用经典非转流原位肝移植术式和背驮式肝移植术式，肾移植为常规术式。病肝切除时注意细致分离第三肝门、创面及时止血。以抗胸腺细胞球蛋白或白细胞介素-2受体单克隆抗体作为免疫诱导，术后服用他克莫司、吗替麦考酚酯及激素维持免疫抑制治疗。患者门诊随访，复查血、尿常规．肝肾功能，他克莫司血药浓度以及移植物B超等。随访时间12—53个月。结果13例手术均成功。术后发生急性排斥反应1例，继发性出血1例，心肌梗死1例（死亡），胸腔积液4例，肺部感染3例（1例死亡）。除死亡病例外，所有并发症经相应治疗后逆转治愈。11例存活者肝肾功能正常，其中存活4年5个月者1例，存活3年以上者2例，2年以上者6例，1年以上者2例。1例49岁患者术后18个月死于心肌梗死，1例52岁患者术后13个月死于肺部巨细胞病毒感染。结论 肝肾联合移植是肝肾功能衰竭的有效治疗手段。娴熟的手术技巧和并发症的及时诊治是肝肾联合移植成功的关键。     

Nephrological indications in combined liver-kidney transplantation

In isolated liver transplantation pretransplant renal failure is a major mortality risk, there are no guidelines at the moment to establish the indications for a combined liver-kidney transplantation (LKT). In irreversible chronic renal failure (CRF) not on dialysis, nephrological evaluation is required to assess the need for a simultaneous kidney transplantation. There are no experiences about the functional contribution of native kidneys post-LKT. Herein we have reported the case of two patients who underwent LKT in 2004 due to CRF, not yet on dialysis. At the moment of LKT, the first patient (polycystic kidney disease) had a glomerular filtration rate (GFR) = 29 mL/min, and the second recipient (vascular nephropathy and diabetes), a GFR = 33 mL/min. In both cases we did not observe delayed graft function. At discharge the serum creatinine was 1.1 and 1.0 mg/dL, respectively, which was maintained during follow-up. In both cases renal scintigraphy with Tc-99 DMSA was performed to evaluate the functional contributions of transplanted versus native kidneys. In the first case scintigraphy at 9 months after LKT demonstrated an 81% contribution from the transplanted kidney, 9% from the right and 10% from the left native kidneys. In the second case, at 3 months after LKT, the functional contributions were 76%, 10%, and 14%, respectively. The transplanted kidney nephron mass may avoid the need for hemodialysis in the early posttransplant period; in the midterm it may help to maintain residual renal function. As in other combined transplant programs (heart-kidney, kidney-pancreas) with irreversible CRF, a GFR < or = 30 to 35 mL/min may be an indication for LKT, but we need more experience.     

临床肝肾移植三例体会

目的　探讨肝肾序贯移植和同期联合移植的手术难点及围手术期处理要点。方法　对2例肾移植术后发生药物性肝损害的病例实施肝移植 ,并对 1例巨大多囊肝、多囊肾的病例实施肝肾联合移植。结果　 2例肾移植术后实施肝移植的病例 ,其中 1例因术后肾功能衰竭导致多器官功能衰竭死亡 ;另 1例术后肝、肾功能良好 ,现已存活 1年。肝肾联合移植病例术中采用肝后腔静脉直接阻断法 ,使重达 10kg的巨大病肝得以顺利切除 ,并采用腔静脉成型术完成改良背驮式肝移植。术后免疫方案采用人源化单克隆抗体达利珠单抗免疫诱导下的以FK5 0 6、霉酚酸酯 (MMF)和激素的三联用药 ,肝、肾功能恢复良好 ,现为术后 6个月。结论　序贯性肝肾移植在术前应该准确评估移植肾功能 ,如果移植肾功能不良 ,应果断选择实施肝肾联合移植。肝后下腔静脉直接阻断法在实施巨大病肝切除时具有较大优势。肝肾联合移植术中及术后建议采用达利珠单抗免疫诱导下的免疫三联用药。     

Renal function outcomes following liver transplantation and combined liver-kidney transplantation

Acute renal failure (ARF) is common immediately after orthotopic liver transplantation (OLT), whereas the incidences of chronic kidney disease (CKD) and end-stage renal disease increase with time. Introduction of the Model for End-stage Liver Disease (MELD) score-intended to prioritize patients with more-severe pretransplantation liver disease in general, and worse pretransplantation renal function in particular-for the allocation of liver grafts led to concerns about compromised patient and allograft survival and increased incidence of postoperative ARF and CKD. Nonetheless, it has been suggested that early OLT of candidates with baseline renal dysfunction improves post-transplantation renal outcomes. For OLT candidates with mild to moderate chronic renal impairment or recent-onset ARF, the decision of whether to perform OLT alone or combined liver-kidney transplantation (CLKT) can be challenging because no single factor has been shown to be predictive of the degree of renal function recovery or CKD progression following successful OLT. In this article, we provide an overview of the literature on renal function outcomes following OLT and CLKT, share our perspectives on the potential predictors of renal dysfunction or nonrecovery of renal function after OLT, and present United Network for Organ Sharing data on patient and allograft outcomes in CLKT recipients in the pre-MELD and post-MELD eras. Mechanisms that might underlie immunological protection of kidney grafts by liver allografts are also discussed.     

肝肾联合移植15例报道

目的探讨肝肾联合移植的适应证和疗效。方法对2001年2月至2003年12月施行肝肾联合移植术的15例患者进行了随访。15例中,乙型肝炎后肝硬化合并肝肾综合征8例、合并尿毒症2例、合并糖尿病肾病1例;多囊肝和多囊肾2例;Caroli病合并多囊肾1例;酒精性肝硬化合并尿毒症1例。对肝肾联合移植患者的手术方式,围手术期并发症,术后急、慢性排斥反应和乙型肝炎复发情况及随访结果进行了分析。结果15例肝肾联合移植术后移植物功能均恢复良好,6个月和1年生存率为100%。1例术前有严重营养不良者,术后给与48d的呼吸机支持后康复。术后创面出血和消化道出血各1例,经非手术治疗后治愈。胆道吻合口狭窄1例,用内镜下球囊扩张术治愈。1例术后2周发生急性移植肝排斥反应,给予激素冲击治疗后得到控制。1例术后30个月时因停用拉米夫定后乙型肝炎复发死于移植肝功能丧失。结论肝肾联合移植是终末期肝病合并慢性肾功能衰竭或肾功能损害的安全有效方法。对乙型肝炎患者术后尽早应用拉米夫定和乙型肝炎病毒免疫球蛋白预防肝炎复发。     

大鼠原位肝、肾一期联合移植模型的建立

目的　建立一种简易可靠的大鼠肝、肾联合移植模型。方法　以SD大鼠作供、受者,以4 ℃乳酸林格液经门静脉和腹主动脉对供者的肝脏和左肾进行原位灌洗,肝下下腔静脉在右肾静脉以下切断。供肝肝上下腔静脉用显微外科技术缝合,双袖套法吻合肝下下腔静脉及门静脉;带瓣左肾动脉与受者的腹主动脉吻合,袖套管法吻合肾静脉;用支架管重建胆道和输尿管。结果　共完成54次大鼠肝、肾一期联合移植手术,其中预实验24 次,正式实验30 次,正式实验的手术成功率为76.7 %,移植肝及肾功能良好。结论　此模型可以用于移植相关研究。     

Controversies in combined liver-kidney transplantation: indications and outcomes

Controversy surrounds simultaneous transplantation of a kidney and a liver because the practice is increasing, and organs for transplant are limited. Not only do recipients of both organs use 2 rather than 1 organ, but the kidney in dual transplantation jumps to the front of a very long kidney wait-list. Furthermore, there is suspicion that some patients who undergo combined liver and kidney transplantation may have reversible renal failure. Likewise, inappropriate liver transplantation in those with end-stage renal disease is possible given the heavy weighting of kidney dysfunction in the calculation of the model for end-stage liver disease score. Thus, a better way to determine the recoverability of renal dysfunction in liver transplant candidates and the degree of liver disease in end-stage renal disease is needed. Standardized strategies for candidate evaluation, selection, and process review are also necessary to improve organ allocation in those with both liver and kidney disease. However, basic and clinical investigation will be needed before an optimal algorithm is possible.     

大鼠肝、肾联合移植模型的建立

目的 建立大鼠肝，肾联合移植模型。方法 选用Wistar大鼠，以4℃乳酸钠林格注射液经门静脉和腹主动脉对供肝和供肾进行原位灌洗。移植时除肝上下腔静脉缝合外，其余血管重建均采用袖套式吻合，将供肾附带的一侧面腹主动脉修剪成椭圆状，方便操作，并满足对等口径吻合，供肾输尿管拖出种入膀胱。结果 共完成35次大鼠原位肝，肾联合移植手术。其中后20次手术成功率为90%，最长存活时间超过5个月。结论 该模型可运用于移植相关研究。     

Significance of a T-lymphocytotoxic crossmatch in liver and combined liver-kidney transplantation

BACKGROUND: In contrast to kidney transplants a positive crossmatch is no contraindication for liver transplantation (OLT). In liver transplantation, antibody mediated rejections are rarely reported and a liver graft is suspected to have protective effects for kidney grafts when transplanted simultaneously. The aim of this study was to evaluate the effect of a positive crossmatch on outcome after OLT and combined liver and kidney transplantation (CLKTx). METHODS: We analyzed retrospectively the impact of a positive crossmatch on graft survival and rejection episodes after OLT (793pats) and CLKTx (18pats, 2.2%). Immunosuppression consisted of either Cyclosporine- or Tacrolimus-based regimens. RESULTS: A total of 50/811 (6%) of patients had a positive crossmatch, 45/793 (5.6%) with liver transplantation alone and 5/18 (28%) of patients with CLKTx. Follow-up ranged from 1 to 122.5 months (median 45.8 months). One- and 5-year graft survival rates of liver transplants alone with a positive crossmatch were 89.6% and 75.3%, respectively and were 88% and 77.5% in crossmatch negative recipients. Additionally, the incidence of acute and steroid-resistant rejection (44% and 15.5%) was not significantly increased in patients with a positive crossmatch when compared with patients with a negative crossmatch (38% and 19%). None of the patients with a positive crossmatch and CLKTx underwent a hyperacute-rejection episode after transplantation, and kidney graft survival 100%. CONCLUSIONS: In conclusion, a positive crossmatch is no contraindication for OLT and CLKTx. Furthermore, not having to wait for results of donor/recipient crossmatching can shorten cold ischemia time and may improve the clinical outcome.     

肝或肾移植术后受者再次行一期肝肾联合移植三例报告

目的 探讨肝或肾移植术后受者再次行一期肝肾联合移植的手术适应证、术后并发症及存活情况.方法 对2003年10月至2008年12月施行的3例肝或肾移植术后再次行一期肝肾联合移植的受者进行随访,并进行文献复习.对其围手术期死亡率、术后并发症及存活情况进行总结.结果 围手术期死亡率为33.3%(1/3).术后并发症:1例因腹腔出血术后第29天死于肺部感染、急性移植肾功能衰竭和多器官功能衰竭;3例患者均发生了肺部感染;无急性排斥反应发生.2例存活患者,从首次移植计算,已经分别存活56个月和228个月;从一期肝肾联合移植计算,已经分别存活40个月和48个月.结论 肝肾联合移植是治疗终末期肝肾疾病的有效方法.肝或肾移植术后受者再次行一期肝肾联合移植是可行的.     

Sequential liver-kidney transplantation

The indications for sequential liver and kidney transplantation have not been well defined. Two categories of patients may benefit from this procedure: patients with primary renal disease associated with hepatic disorders (glomerulonephritis, tubulointerstitial nephritis, metabolic diseases, and structural diseases) and patients who develop renal failure after liver transplantation. Chronic renal failure is a frequent long-term complication after liver transplantation. End-stage renal disease develops in 2% to 10% of cases by 10 years after transplantation. Kidney transplantation appears to be a better option than dialysis for the treatment of end-stage renal disease after liver transplantation. In contrast, survival rates, after kidney transplantation are significantly lower among liver transplant patients than primary-only kidney transplant recipients. Considering the donor shortage, kidney transplantation should be cautiously considered in liver transplantation patients. New immunosuppressive drugs and protocols are needed to reduce chronic renal failure after liver transplantation.     

Sirolimus rescue of renal failure in children after combined liver-kidney transplantation

Background: Calcineurin inhibitors (CNI) are the main immunosuppressive drugs in solid organ transplantation. However, their use is hampered by side effects like nephrotoxicity. We report an exceptional experience with three children treated with sirolimus after combined liver and kidney transplantation with prolonged renal failure and CNI-associated nephrotoxicity. Patients and results: Two girls experienced prolonged renal graft failure after combined liver-kidney transplantation for 11 and 12 weeks. Repeated biopsies did not show any rejection but did exhibit tubular damage and acute CNI-toxicity. A boy with hyperoxaluria after liver and (a third) renal transplantation experienced acute renal graft failure after an early steroid-resistant rejection. All children were switched to sirolimus-based immunosuppression and cessation of CNI therapy, which was followed by rapid improvement of renal function. Rejection of liver or kidney did not occur after CNI withdrawal. Sirolimus was commenced with 3 mg/m²/day in two doses and resulted in reasonable drug exposure. However, drug monitoring was required to adjust sirolimus dosage. Summary: Prolonged renal failure after transplantation with severe CNI toxicity may be salvaged successfully with sirolimus-based immunosuppression.     

Thirteen cases of liver-kidney transplantation

Combined kidney-liver transplantation is currently the best therapeutic option for patients with end-stage kidney and liver disease. We present our experience of kidney-liver transplantation in a series of 13 patients. The most frequent indications were familial amyloidotic polyneuropathy (FAP) and polycystosis of the liver and kidney. The 1- and 5-year survival rates of the liver grafts were 75% and 67%, respectively, with no kidney losses during follow-up.     

大鼠肝、肾联合移植模型的建立

目的探讨大鼠肝、肾联合移植模型的建立方法及并发症的预防。方法以SD大鼠为供、受者,用0~4℃乳酸钠林格注射液经腹主动脉对供肝和供肾进行原位灌洗,整块切取供鼠的肝、肠、胰、脾及右肾,浸泡在保存液中修整。移植时血管重建全部采用袖套式吻合,应用支架行胆总管吻合,输尿管采取所附带的膀胱瓣与受者的膀胱吻合。结果共行大鼠肝、肾联合移植110次,其中预实验50次,受鼠死亡18只;正式实验60次,受鼠死亡5只,余下的大鼠均存活30d以上,存活率为91.7%(55/60)。结论袖套法建立大鼠肝、肾联合移植模型降低了手术难度,具有血管吻合时间短、血流通畅、无肝期短等优点,术前准备、术中操作及术后处理等各环节对于并发症的预防具有重要作用。     

肝、肾联合移植六例报告

目的 交流肝、肾联合移植的体会。方法 对6例患者施行肝、肾联合移植，其原发病4例为慢性肾炎、乙型肝炎后肝硬化，1例为乙型肝炎相关性肾炎、原发性肝癌，1例为多囊肝、多囊。肾。术后应用环孢素A（或他克莫司）、霉酚酸酯及甲泼尼龙预防排斥反应，4例乙型肝炎后肝硬化患者同时口服拉米夫定，并短期使用抗乙型肝炎球蛋白。结果 术后6例移植肝功能迅速恢复正常，5例移植肾功能在术后1周内恢复正常，1例移植肾功能恢复延迟，经支持性血液透析治疗，于术后第52d血肌酐恢复正常。术后6例患者出现胸腔积液，其中2例需穿刺引流；2例发生细菌性肺炎和卡氏肺囊虫肺炎；3例术后早期需行降脂治疗。目前6例患者均存活，且移植肝和移植肾功能均正常。1例术前群体反应性抗体（PRA）为23％，术后PRA稳定在8％左右。4例乙型肝炎后肝硬化的患者术后血清乙型肝炎表面抗原和乙型肝炎病毒DNA转阴。结论 肝、肾联合移植治疗终末期肝、肾疾病具有较好的近期疗效。