Sequential combined liver-kidney transplantation for a one-year-old boy with infantile primary hyperoxaluria type 1

We present the case of a one-year-old male patient with infantile primary hyperoxaluria type 1 (PH1). The patient visited hospital because of growth delay and poor feeding when he was six months old, and was diagnosed as PH1 with chronic renal failure. He underwent peritoneal dialysis until receiving a living-related liver transplantation when he was seventeen months old, and after the operation, underwent hemodialysis or hemodiafiltration four times per week. Six months after the liver transplantation, his serum oxalate level decreased to around 20 micromol/l and a living-related kidney transplantation was successfully performed. Nine months have passed since the kidney transplantation, and the patient's liver and kidney functions have been good and his growth and development much better than before the sequential liver and kidney transplantation. However, his serum and urine oxalate levels remained high and he has required high dose hydration to prevent deposition of calcium oxalate crystals in his grafted kidney. The key-points for treating infantile PHI patients are summarized as follows; 1) make a precise diagnosis as soon as possible, 2) perform a combined liver-kidney transplantation successfully, 3) conduct careful monitoring of the serum and urine oxalate levels and continue adequate hydration after kidney transplantation until the serum and urine oxalate levels normalize. Furthermore, cooperation between the medical staff and the patient's family seems to be essential.     

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。     

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.     

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.     

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.     

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。     

肝肾联合移植的单中心经验总结

目的 分析单中心肝肾联合移植(SLKT)的治疗效果.方法 1999-2010年间共实施SLKT 21例,患者的原发疾病分别为多囊病11例,病毒性肝炎后肝硬化合并肝肾综合征5例,慢性肾炎肾功能衰竭合并肝硬化2例,肾移植术后移植肾功能丧失合并肝硬化2例,肝炎后肝硬化合并糖尿病肾病1例.统计患者的资料,与同期同中心"中国肝移植注册网站"收录的肝炎后肝硬化行肝移植的133例(LT组)和"中国肾移植科学登记系统"收录的尸体肾移植609例(KT组)进行对比,分析各组受者术前状态和预后的差异.结果 SLKT组术前终末期肝病模型(MELD)评分为21.3±5.5,血肌酐为(516.0±329.9)mmol/L;LT组术前MELD评分为20.6±9.9,血肌酐为(111.4±138.1)mmol/L,与SLKT组相比较,血肌酐的差异有统计学意义(P＜0.01).SLKT组中,3例分别于术后2周、半年和5年因感染而死亡,1例因多器官功能衰竭而死亡,1例于术后5年自行停药,因排斥反应而死亡.SLKT组术后1年内移植肾急性排斥反应的发生率为零,KT组为6 %(P＞0.05).术后SLKT组移植肾功能延迟恢复的发生率为9.5 %,KT组为17.3 %(P＞0.05).SLKT组术后1、3和5年的受者存活率分别为87.7 %、67.8 %和67.8 %,LT组分别为84.2 %、73.5 %和69.4 %(P＞0.05).结论 SLKT是终末期肝、肾疾病的有效、安全的治疗方法.

Abstract：

Objective To analyze the curative effect of simultaneous liver and kidney transplantation (SLKT) for patients with end-stage liver and kidney diseases and liver cirrhosis patients with hepatorenal syndrome.Methods All SLKTs (n=21) performed at our center from January 1999 to December 2010 were reviewed and SLKT outcomes were compared with those of kidney transplantation (KT) (n=609) and liver transplantation (LT) (n=133) performed during the same period.Results There were 3 deaths due to infection 2 weeks, 6 months and 5 years respectively after operation. One patient died due to multiple organ dysfunction syndrome 2 weeks after operation. One patient was dead 5 years after operation because of rejection. MELD level between SLKT and LT had no significant difference, but serum creatinine in SLKT group was significantly higher than in LT group (516.0±329.9 vs 111.4±138.1 mmol/L, P<0.01). The 1-year acute kidney rejection rate and rate of delayed graft function (DGF) of the kidney had no significant difference between SLKT group (0 vs 9.5 %) and KT group (6 % vs 17.3 %). There was no significant difference in one-, 3- and 5-year patient survival rate between SLKT group (87.7 %, 67.8 % and 67.8 %) and LT group (84.2 %, 73.5 % and 69.4 %).Conclusion SLKT is a safe and effective treatment for end-stage liver and kidney diseases.     

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.     

Results of combined and sequential liver-kidney transplantation

Experience with combined liver-kidney transplantation (L-KTx) has increased, but controversy regarding this procedure continues because the indications are not clearly defined yet. Between 1984 and 2000, 38 patients underwent simultaneous L-KTx and 9 patients underwent sequential transplantation, receiving either a liver before a kidney or a kidney before a liver. Main indications for a simultaneous procedure were polycystic liver-kidney disease with cirrhosis and coincidental renal failure. The main indications for sequential procedure were cirrhosis caused by viral infection for the liver and glomerulonephritis for the kidneys. Outcomes in these patients were evaluated retrospectively. Regarding simultaneous transplantation, 28 (73.7%) long-term survivors were followed up for 0.7 to 12.5 years. Currently, 24 (63.2%) patients are alive with good liver function. Fourteen patients died; 10 patients died in the early postoperative phase because of septic complications, and most of them were cirrhotic with a poor preoperative clinical status. Currently, 2 of the surviving patients (8%) have returned to dialysis, 4 (17%) have reduced renal function, and 18 (75%) have good renal function. Five liver and 2 kidney retransplantations were performed during the follow-up. In cases of sequential grafting, patients undergoing kidney transplantation in the presence of a previously transplanted stable liver did better than those who underwent liver transplantation after kidney transplantation. When liver transplantation was performed early and electively before substantial worsening, combined L-KTx is a safe procedure offering excellent long-term palliation. (Liver Transpl 2003;9:1067-1078.)     

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。     

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。     

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。     

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。     

肝肾联合移植13例临床分析

目的 探讨肝肾联合移植的适应证、手术并发症及生存情况.方法 回顾性分析2003年10月至2008年12月施行的13例肝肾联合移植患者的临床资料,分析围手术期死亡率、并发症情况及生存情况.结果 13例肝肾联合移植患者围手术期死亡率30.8%(4/13).术中、术后腹腔出血4例(30.8%);肺部感染7例(53.8%);移植肾急性排斥反应1例(7.7%).本组随访4.4～60个月,中位数40个月.存活1年以上8例,2年以上6例,3年以上5例,4年以上3例,5年以上1例.肝肾联合移植前有1例患者经历肝移植(例2)和2例患者经历肾移植(例3、例4),例4患者于肝肾联合移植术后第29天死于肺部感染、多器官功能衰竭,例2和例3肝肾联合移植术后分别存活40 m、48 m.结论 肝肾联合移植是治疗终未期肝肾疾病的有效方法.肝/肾移植术后再行肝肾联合移植是可行的.

Abstract：

Objective To investigate the indications, complications and survival results of combined liver-kidney transplantation. Methods From Oct 2003 to Dec 2008, the clinical data of 13 patients who underwent combined liver-kidney transplantation (CLKTs) were retrosptiverly analyzed in our institution. The perioperative mortality rate, complications and the result of follow-up were analyzed.Results The perioperative mortality rate (within 30 days) was 30.8% (4/13). Postoperative complications included intrabdominal bleeding in 4 patients ( 30. 8% ); pulmonary infection in 7 patients (53.8%); acute renal rejection in one (7. 7% ). Survivors were followed up from 4.4 to 60 months, with the median time of 40 months. Eight patients have survived more than 1 year; six patients have survived more than 2 years; five of them have survived for more than 3 years; and three of them have survived for more than 4 years, with one surviving for more than 5 years. One patient had undergone liver transplantation ( case 2 ) and two patients had had kidney transplantations ( case 3 and case 4 ) before this CLKTs.Postoperatively case 4 died of pulmonary infection and multiple organ failure at day 29, while case 2 and case 4 survived respectively 40 m, 48 m after CLKTs. Conclusions CLKTs is an effective therapy for end-stage liver and kidney disease. CLKTs for patients with irreversible liver and renal insufficiency after initial liver transplantation or kidney transplantation was feasible.     

Combined liver-kidney transplantation in polycystic disease: case reports

Polycystic disease causes a progressive decrease in renal function and liver degeneration. The progression of the disease evolves separately between organs and transplantation options vary: simultaneous or sequential liver-kidney transplantation or single-organ transplantation. From September 2006 to June 2007 3 combined liver kidney transplantations (CLKT) were performed for polycystic disease with end-stage renal disease: 2 with polycystic liver disease, and 1 with hepatic failure due to congenital hepatic fibrosis. The widest dimensions of the polycystic liver of 50 and 60 cm diameter were due to extensive cystic degeneration. We performed 1 simultaneous CLKT and 2 sequential transplantations: 1 liver after kidney, and 1 kidney after liver. At present all patients are alive with 100% graft function. Median creatinine level at discharge was 0.9 mg/dL (ranges, +/-0.2). Good liver graft function was reported in all 3 cases. Transplant benefit in polycystic liver-kidney disease has been already demonstrated; conservative surgical options may result in a high incidence of complications in highly involved polycystic livers. Delaying transplantation results in a more difficult surgical technique, a higher rate of postoperative complications, and a disturbance of optimal graft retrieval because of the worse preoperative condition of the patients.