Simultaneous liver-kidney transplant for combined renal and hepatic end-stage disease

INTRODUCTION: After the first combined liver-kidney transplantation (CLKT) reported by Margreiter in 1984, it became clear that renal failure was no longer an absolute contraindication. OBJECTIVE: Our goal was to assess our results with combined liver-kidney transplant.Among 875 liver transplants performed between May 1986 and October 2002, there were 17 cases (1.96%) of combined liver-kidney transplant. RESULTS: With a mean follow-up of 42.2+/-29 months (range, 1-90), six patients had died (mortality: 37.5%). There were four (25%) operative in-hospital deaths, and two late mortality cases (beyond the month 6 after hospital discharge). The causes were sepsis (four cases, three postoperative and one in later follow-up), refractory heart failure (one postoperative), and recurrent liver disease (HCV-induced severe recurrence) during follow-up one). Actuarial survival (calculated for those who survived the postoperative period) was 80%, 71%, and 60% at 12, 36, and 60 months. Actuarial mean survival time was 60 months (95%IC:47-78). Neither the sex, the UNOS status, the etiology of liver disease, the etiology of renal failure, the type of hepatectomy (piggy back vs others) or the type of immunosuppression (P=.83) were related to long-term survival according to the log-rank test. A control group of 48 patients was constructed with subjects who underwent liver transplantation immediately before or after the combined transplant. A total (two cases after the CLKT and one case prior to). There were no differences in survival. CONCLUSION: Combined liver-kidney transplant represents a proper therapeutic option for patients with simultaneously failing organs based on long- and short-term outcomes.     

胰肾联合移植治疗Ⅰ型糖尿病合并终末期肾病

目的 探讨胰肾联合移植治疗Ⅰ型糖尿病合并终末期肾病的临床效果。方法 ８例Ⅰ型糖尿病合并终末期肾病的患者接受胰肾联合移植,平均年龄４３．４６岁,２例合并视网膜病变,双目失明,病史２～２２年。胰腺移植于右髂窝,胰腺外分泌经膀胱引流,肾脏移植于左髂窝。免疫抑制方案开始四联用药,以后三联用药继续治疗。结果 ８例虱其中７例术后即不需要应用胰岛素,空腹血糖可维持在正常范围,１例术后应用胰岛素４０ｄ后停用。１例     

Simultaneous liver-kidney versus liver transplantation alone in patients with end-stage liver disease and kidney dysfunction not on dialysis

Background

Since implementation of the Model for End-stage Liver Disease (MELD), the number of simultaneous liver-kidney transplantations (SLKT) has increased in the United States. However, predictors and survival benefit of SLKT compared to liver transplantation alone (LTA) are not well defined.

Methods

Organ Procurement and Transplantation Network data of patients with end-stage liver disease (ESLD) with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² who had not been on dialysis while on the waiting list and underwent liver transplantation between 2002 and 2008 were analyzed. To identify predictors of undergoing SLKT versus LTA, multiple logistic regression analysis was performed. Cox proportional hazards regression analysis was used to assess the association between SLKT and post–liver transplant patient and graft survival.

Results

The study cohort comprised 5443 patients; 262 (5%) underwent SLKT and 5181 (95%) underwent LTA. Adjusting for potential confounders, patients who underwent SLKT were 34% less likely to die after liver transplantation than those who underwent LTA (hazard ratio [HR] = 0.66, P = .012) and 33% less likely to have liver graft failure than those who underwent LTA (HR = 0.67, P = .010). Among those who underwent SLKT, 1-, 3-, and 5-year kidney graft survival probabilities were 88%, 80%, and 77%, respectively. Black race and diabetes were associated with a higher likelihood of SLKT versus LTA; female sex, a higher eGFR, and higher MELD score reduced the likelihood of SLKT.

Conclusions

Among those with ESLD and kidney dysfunction not on dialysis, post–liver transplant patient and liver graft survivals of patients who underwent SLKT were superior to those of patients who underwent LTA. Whether this reflects differences in the two groups that could not be adjusted in survival models or a specific effect of kidney dysfunction cannot be established.     

Simultaneous kidney-pancreas transplantation for end-stage renal disease patients with insulin-dependent diabetes and detectable C-peptide

Introduction

There is controversy regarding the place of simultaneous pancreas-kidney (SPK) transplantation in end-stage renal disease (ESRD) patients with insulin-dependent diabetes mellitus (IDDM) and detectable c-peptide. We sought to compare outcomes of recipients with and without pretransplantation c-peptide.

Methods

This retrospective single-center review included consecutive primary SPK transplantations performed between September 2007 and May 2010. Demographic characteristics and outcomes were compared between recipients with and without pretransplantation c-peptide.

Results

Seven of 25 (28%) consecutive SPK transplant recipients with a diagnosis of IDDM and ESRD had detectable c-peptide prior to transplantation. The mean c-peptide level was 6.3 ± 6.1 ng/mL. For those recipients with and without c-peptide, mean age at diagnosis of IDDM (12.4 ± 7.8 vs 17.1 ± 6.6 years; P = not significant [NS]), duration of IDDM prior to transplantation (30 ± 10 vs 23 ± 9 years; P = NS), and body mass index (25.9 ± 4.5 vs 26.7 ± 4.5 kg/m²; P = NS) were equivalent between the groups. With a median follow-up of 17 months (range, 3–35 months) there was 1 graft loss (due to cardiovascular death) among the 25 patients. At the most recent follow-up, for recipients with and without c-peptide, both the mean serum creatinine (1.3 ± 0.6 vs 1.0 ± 0.2 ng/mL; P = NS) and the mean HbA1c level (5.3 ± 0.4 vs 5.3 ± 0.5; P = NS) were equivalent between the groups.

Conclusion

For nonobese ESRD patients diagnosed with IDDM at a young age, the presence of detectable c-peptide should not influence the decision to proceed with SPK transplantation.     

肾移植联合成人胰岛细胞移植治疗糖尿病肾病七例报告

目的 建立新型成人胰岛细胞分离纯化方法和无激素免疫抑制方案.观察.肾移植联合胰岛细胞移植治疗1型糖尿病肾病的安全性与有效性.方法 全氟化碳液与威斯康星大学器官保存液双层冷藏胰腺,Liberase酶消化,COBE 2991型专用胰岛细胞分离机分离及连续密度梯度纯化,获取高纯度与高活性的胰岛细胞.常规方法行尸体肾移植,次El采用外科方法将短期培养的胰岛细胞经门静脉移植到肝脏内,采用无激素免疫抑制治疗.术后定期监测血糖与胰岛素用量、C肽与糖化血红蛋白水平以及肝肾功能.结果 23个胰腺均成功分离胰岛细胞,平均数量30万胰岛当量(IEQ)、纯度92%、活率95%、刺激指数3.16,病原学结果均阴性.7例1型糖尿病肾病患者共行胰岛细胞移植12次(移植1次3例、2次3例、3次1例).每次移植胰岛数量平均为11 820 IEQ/kg.采用阿来佐单抗诱导、西罗莫司和小剂量他克莫司、无激素免疫抑制治疗.随访1.5～3.0年,4例完全撤除胰岛素,3例胰岛素用量较术前减少＞70%.术后血糖稳定维持在正常水平,C肽均＞0.166nmol/L,糖化血红蛋白正常,肝肾功能正常.结论 新型成人胰岛细胞分离纯化方法可靠,胰岛细胞联合肾移植治疗1型糖尿病肾病安全、有效.     

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.     

Simultaneous liver-kidney transplantation for glycogen storage disease type IA (von Gierke's disease)

INTRODUCTION: Glycogen storage disease type Ia (GSDIa) is due to the deficiency of glucose-6-phosphatase activity in the liver, kidney, and intestine. Although significant progress has been achieved in the management of patients with GSDIa, complications still emerge. The potential for development of liver adenomatosis and kidney failure makes these patients candidates for simultaneous liver-kidney transplantation (SLKT). Herein, we describe such a transplantation in a patient affected by this rare storage disease. METHODS: A 25-year-old female patient with GSDIa developed hepatic adenoma and kidney failure despite dietary therapy. The patient underwent an SLKT from a cadaveric donor. RESULTS: The operative time was 8 hours without hemotransfusion. Only a transitory lactic acidosis was observed. Laboratory results normalized on postoperative day 7. The patient was discharged on postoperative day 9. After 4 months, the patient is in good condition with well-functioning kidney and liver allografts. CONCLUSION: Patients with end-stage renal disease secondary to GSDIa should be considered for SLKT, especially when the disease is in an early stage.     

胰肾联合移植治疗糖尿病终末期肾病11例临床分析

目的：探讨胰肾联合移植（SPK）治疗糖尿病合并终末期肾病的临床效果。方法：回顾性分析2016年11月至2019年3月11例糖尿病合并终末期肾病患者行SPK的临床资料,总结手术疗效以及并发症情况。结果：所有患者均接受随访,资料统计截至2019年12月1日,随访观察9～37月,人、肾、胰腺存活率分别为100%、100%、91%。11例患者术后1月血肌酐（101±28）μmol/L;末次复查血肌酐（96±24）μmol/L,糖化血红蛋白为（5.6±0.5）%。至资料统计截止时间,10例患者移植肾功能正常,1例患者新发移植肾肾病（血肌酐71～202μmol/L）。术后并发胰腺血栓形成2例,其中1例经肠系膜下静脉自脾静脉中取出血栓,胰腺功能恢复;另1例行移植胰腺切除。胰腺门静脉扭转1例,胰腺排斥反应1例,胰周脓肿1例,消化道出血1例,切口愈合不良5例。9例患者术后空腹、餐后血糖均正常,1例患者午餐后血糖稍高,口服二甲双胍血糖控制可。结论：SPK治疗糖尿病合并终末期肾病疗效确切,但围手术期并发症发生率较高,积极防治围手术期并发症可有效提高手术成功率。     

Simultaneous pancreas-kidney transplantation reduces excess mortality in type 1 diabetic patients with end-stage renal disease

BACKGROUND: Diabetic renal disease continues to be the most significant cause of end-stage renal disease (ESRD) in the United States. Renal transplantation improves diabetic ESRD patient survival; however, the diabetic state remains associated with poor patient survival. Simultaneous pancreas-kidney (SPK) transplantation can restore normoglycemia and thus may improve outcomes. METHODS: We assessed the impact of SPK on age-range-matched type 1 diabetic patients who underwent renal transplantation at a single center. The observed/expected life span and annual mortality rates (AMRs) were used as measures of survival. A Cox proportional hazards analysis was used to analyze the impact of potential variables on mortality in SPK recipients. RESULTS: SPK transplantation (N = 335) increased the observed/expected life span compared with diabetic cadaveric (DM-Cad, N = 147) and live-donor (DM-Live, N = 160) transplant recipients (P = 0.004) and significantly reduced the AMRs (SPK, 1. 5%; DM-Cad, 6.27%; DM-Live, 3.65%, P = 0.008, SPK vs. other DM). Moreover, the SPK observed/expected life span and AMR were not significantly different from that of age-range-matched nondiabetic transplant recipients (N = 492). The only variable that was significantly associated with patient survival was discharge serum creatinine (relative risk 1.16, P < or = 0.0154). CONCLUSION: These data demonstrate that SPK improves the ability for type 1 diabetic patients to live more of their expected life span. This suggests that glycemic control, even as a late intervention in a diabetic patient's lifetime, may beneficially affect survival.     

肝肾联合移植治疗巨大多囊肾合并多囊肝并发肝肾功能衰竭

目的 总结巨大多囊肾合并多囊肝并发肝肾功能衰竭行肝肾联合移植的临床经验.方法 对8例巨大多囊肾合并多囊肝并发肝肾功能衰竭的患者进行肝肾联合移植,男性5例,女性3例;年龄41～67岁,平均52.8岁.先肝后肾采用经典非转流原位肝移植6例,先肾后肝并采用背驮式肝移植2例.术后对急性排斥反应、并发症、肝肾功能、人/肝/肾存活率等临床疗效进行长期随访.结果 随访28～65个月,8例患者均存活,肝肾功能正常.存活5年以上2例,4年以上2例,2年以上4例.围手术期并发胸腔积液2例,肺部金黄色葡萄球菌感染1例,均对症治疗后痊愈.截至随访终点,未发现移植物急性排斥反应.结论 巨大多囊肾合并多囊肝并发肝肾功能衰竭的患者,肝肾联合移植术是安全有效的治疗方法.     

Kidney transplantation for end-stage renal failure in liver transplant recipients with hepatitis C viral infection

BACKGROUND: End-stage renal failure after successful liver transplantation (LTx) has been described in up to 5% of patients. Kidney transplantation (KTx) has been the treatment of choice in these cases. However, in recipients infected with hepatitis C virus (HCV), the augmentation of immunosuppression after KTx may result in an increased viral load. This, in turn, may adversely affect the liver allograft. METHOD: The present study retrospectively examined the outcome in 17 patients (3 females and 14 males, mean age 51.1+/-11.3 years) who received KTx after LTx. The mean interval from LTx to KTx was 57.6+/-32.1 months. The mean follow-up was 41.7+/-20.5 months after KTx, and 99.6+/-37.7 months after LTx. Sixteen of the 17 patients received tacrolimus-based immunosuppression at the time of KTx. RESULTS: During the follow-up period, one patient underwent combined liver and kidney retransplantation 3.7 years after KTx and 12.7 years after LTx. She subsequently died secondary to primary nonfunction. Four other patients died, two of lung cancer, one of pancreatitis/sepsis, and one of severe depression leading to noncompliance. A total of 29 episodes of biopsy-proven acute renal allograft rejection (1.7 episodes/ patient) were encountered and treated with steroids. Seven patients experienced a rise in liver function tests during the period of increased steroid dosage. Four patients received no treatment, and their liver function returned to baseline. The remaining three were treated with interferon. Overall 1- and 3-year actuarial patient and liver allograft survival was 88% and 71% (after renal transplantation); corresponding 1- and 3-year actuarial graft survival was 88% and 61%. Twelve patients are alive with normal liver function. One patient is on dialysis, because of renal allograft loss to noncompliance. CONCLUSION: In this series, LTx recipients with HCV infection were able to undergo KTx with a reasonable degree of success. KTx should be offered for end-stage renal failure after LTx, even in the presence of HCV infection, to individuals with stable liver function and no signs of liver failure.     

肝肾联合移植治疗巨大多囊肾合并多囊肝并发肝肾功能衰竭

目的 总结巨大多囊肾合并多囊肝并发肝肾功能衰竭行肝肾联合移植的临床经验.方法 对8例巨大多囊肾合并多囊肝并发肝肾功能衰竭的患者进行肝肾联合移植,男性5例,女性3例;年龄41～67岁,平均52.8岁.先肝后肾采用经典非转流原位肝移植6例,先肾后肝并采用背驮式肝移植2例.术后对急性排斥反应、并发症、肝肾功能、人/肝/肾存活率等临床疗效进行长期随访.结果 随访28～65个月,8例患者均存活,肝肾功能正常.存活5年以上2例,4年以上2例,2年以上4例.围手术期并发胸腔积液2例,肺部金黄色葡萄球菌感染1例,均对症治疗后痊愈.截至随访终点,未发现移植物急性排斥反应.结论 巨大多囊肾合并多囊肝并发肝肾功能衰竭的患者,肝肾联合移植术是安全有效的治疗方法.     

Simultaneous kidney-pancreas transplantation: The preferred option for patients with type I diabetes mellitus and approaching end-stage renal disease

Diabetes mellitus is a chronic disease often leading to disabling microvascular and macrovascular complications. Intensive treatment with insulin can only delay the progression of these complications. Normalization of the glucose homeostasis will reduce the cardiovascular morbidity and mortality. At this time, whole-pancreas transplantation is the only option to achieve long-term insulin independence, resulting in an improvement or stabilization of the microvascular and, at least partly, the macrovascular lesions. Therefore, simultaneous kidney-pancreas transplantation has become the preferred treatment option for selected patients with type I diabetes mellitus and approaching end-stage renal disease. With the improving results of isolated pancreas transplantation, this procedure may be offered with increasing frequency to diabetics with a good functioning kidney transplant or to diabetics with overt diabetic nephropathy but preserved renal function. In this review we describe recipient and donor selection criteria, some surgical techniques, survival rates, and the currently used immunosuppressive protocols, and at the end we propose a treatment strategy.     

Living related renal transplantation for end-stage renal disease after liver transplantation from a brain-dead donor

We report a case in which a living related renal transplantation was successfully performed for end-stage renal disease that had progressed after a liver transplantation from a brain-dead donor for liver cirrhosis associated with type C hepatitis. Because the transplanted liver function had been excellent with the use of tacrolimus and mycophenolate mofetil, the same immunosuppressive agents with prednisolone were employed for the renal transplantation. Both grafts are functioning well without recurrence of hepatitis at 10 months after the renal transplantation. From our experience, renal transplantation should not be contraindicated even if the patient has undergone liver transplantation or has hepatitis C viral infection.     

Simultaneous robotic kidney transplantation and bariatric surgery for morbidly obese patients with end-stage renal failure

Patients with obesity have limited access to kidney transplantation, mainly due to an increased incidence of surgical complications, which could be reduced with selective use of robotic-assisted surgery. This prospective randomized controlled trial compares the safety and efficacy of combining robotic sleeve gastrectomy and robotic-assisted kidney transplant to robotic kidney transplant alone in candidates with class II or III obesity. Twenty candidates were recruited, 11 were randomized to the robotic sleeve gastrectomy and robotic-assisted kidney transplant group and 9 to the robotic kidney transplant group. At 12-month follow-up, change in body mass index was –8.76 ± 1.82 in the robotic sleeve gastrectomy and robotic-assisted kidney transplant group compared to 1.70 ± 2.30 in the robotic kidney transplant group (P = .0041). Estimated glomerular filtration rate, serum creatinine, readmission rates, and graft failure rates up to 12 months were not different between the two groups. Length of surgery was longer in the robotic sleeve gastrectomy and robotic-assisted kidney transplant group (405 minutes vs. 269 minutes, p = .00304) without increase in estimated blood loss (120 ml vs. 117 ml, p = .908) or incidence of surgical complications. Combined robotic-assisted kidney transplant and sleeve gastrectomy is safe and effective compared to robotic-assisted kidney transplant alone.     

Hyperleptinaemia of end-stage renal disease is corrected by renal transplantation

Background: Previous studies have reported that patients with end-stage renal disease (ESRD) have elevated plasma leptin concentrations, but the cause and significance of the elevations are unknown. We studied leptin concentrations in 29 adults undergoing renal transplantation, to determine if restoration of renal function reduced leptin concentrations in ESRD. Methods: Leptin concentrations were measured by radioimmunoassay in plasma specimens collected within 1 week before transplant, 6 days post-transplant, and 60 days post-transplant. Results: Plasma letpin concentrations were higher in both male and female ESRD patients compared with a control population of similar age and body mass index (BMI), but most of the disparity was due to a minority of patients with grossly elevated concentrations; the majority of ESRD patients had normal or near-normal leptin concentrations afer accounting for their adiposity with BMI. Six days after successful renal transplantation, average plasma leptin concentrations decreased to control levels. The grossly elevated pretransplant concentrations in a minority of patients were greatly reduced in relation to BMI, and the reduction persisted to 60 days post-transplant. The decrease in creatinine with transplant did not correlate with the decrease in leptin. Conclusions: These results demonstrate that restoration of renal function in ESRD patients reduces hyperleptinaemia, which provides further evidence of a cause/effect relationship between impaired renal function and abnormal leptin metabolism.      

Gastrointestinal and hepatic disorders in end-stage renal disease and renal transplant recipients

Gastrointestinal and hepatic disorders are commonly associated with end-stage renal disease, hemodialysis, and renal transplantation. Recent studies indicate that the prevalence of dyspepsia, ulcer disease, and Helicobacter pylori gastritis is not significantly different from the general population. Bleeding from angiodysplasia, however, is more common in chronic renal failure, as is gastroparesis. The prevalence of chronic hepatitis B has been dramatically reduced among hemodialysis patients since the advent of universal precautions. Response rates to hepatitis B vaccine in noninfected patients, however, are lower in these individuals. Chronic hepatitis C is found in 20% to 25% of HD patients worldwide and accounts for approximately 1% of all infected individuals. Levels of alanine aminotransferase and aspartase aminotransferase are often within normal limits but may be elevated compared with a patient's preinfection levels. Dialysis has been shown to reduce the level of hepatitis C virus viremia. Treatment is similar to non-renal failure patients, although interferon is generally not used in renal transplant recipients owing to concerns of graft failure.     

Kidney transplantation improves arterial stiffness in patients with end-stage renal disease

Background

Cardiovascular disease (CVD) is the leading cause of mortality among the patients with end-stage renal disease (ESRD). Arterial stiffness is a well-accepted predictor of cardiovascular mortality in general population and ESRD patients. The aim of this study was to compare the change of arterial stiffness in kidney transplant recipients (KTRs) and ESRD patients, and further investigate the impact of kidney transplantation (KT) on arterial stiffness.

Methods

A total of 138 maintenance hemodialysis patients, 198 KTRs and 75 healthy volunteers were enrolled in this study. The carotid-femoral pulse wave velocity (CF-PWV) and carotid-radial PWV (CR-PWV) were determined, and the correlations of PWV with biochemical parameters were analyzed.

Results

CF-PWV was highest in the maintenance hemodialysis patients, but similar between KTRs and healthy volunteers. Bivariate correlation analysis among KTRs demonstrated that CF-PWV was positively correlated with high level of peripheral diastolic blood pressure, pulse pressure, mean artery pressure, BUN and HDL, but negatively correlated with albumin. Univariate polytomous logistic regression analysis showed that age, BMI, systolic blood pressure, pulse pressure, length of KT and BUN were associated with the increase of CF-PWV value.

Conclusions

Aortic stiffness could be improved after KT. Meanwhile, age, BMI, systolic blood pressure, pulse pressure, length of KT and BUN were independent predictors of the increase of CF-PWV in KTRs.