达昔单抗预防肾移植术后急性排斥反应的效果

目的　探讨达昔单抗 (Dac ,赛尼哌 )在预防肾移植术后急性排斥反应中的作用。　方法　 2 92例肾移植患者随机分为达昔单抗治疗组 (94例 )与对照组 (198)例 ,分析 2组移植肾功能、急性排斥反应发生情况以及外周血T细胞亚群的变化。　结果　术后 1、6及 12个月时达昔单抗组移植肾功能优于对照组 ,术后 12个月时 2组SCr浓度分别为 (133.2± 4 6 .8)和 (16 5 .7± 5 5 .2 ) μmol/L ,差异有统计学意义 (P <0 .0 5 )。术后 6个月时达昔单抗组急性排斥反应发生率为 2 3.4 % ,对照组为38.4 % ,差异有统计学意义 (P <0 .0 5 ) ;术后 2组CD+ 3 与CD+ 4 表达均下降 ,但差异无统计学意义 (P>0 .0 5 )。　结论　达昔单抗可以降低急性排斥反应发生率 ,改善移植肾功能 ,对T细胞亚群无明显影响。     

维生素E酯预处理对小鼠原位脂肪肝移植的影响

目的　探讨供者用维生素E酯 (VES)预处理对原位小鼠脂肪肝移植的保护作用及其机理。方法　建立小鼠原位肝移植模型。随机分为正常小鼠对照组 (n =8)、肥胖小鼠对照组 (n =8)、非脂肪肝移植组 (n =12 )、脂肪肝移植组 (n =12 )、VES预处理脂肪肝移植组 (n =12 )。术后检测各组血清丙氨酸转氨酶 (ALT)、天冬氨酸转氨酶 (AST)相对水平 ;肝脏组织HE染色 ,油红O染色脂肪定量 ,ATP含量及解偶联蛋白 2 (UCP 2 )水平。结果　VES预处理脂肪肝移植组移植后 2h存活率为4 5 % ,而脂肪肝移植组为 2 5 % ,差异有显著性 (P <0 .0 5 ) ;VES预处理脂肪肝移植组血清ALT与AST水平与ATP浓度分别为 (32 33± 10 6 5 )U/L、(4386± 92 4 )U/L、0 .19± 0 .0 1,而脂肪肝移植组分别为 (832 0± 4 6 5 5 )U/L、(6 4 94± 2 6 5 5 )U/L、0 .13± 0 .0 1,差异有显著性 (P <0 .0 5 ) ;VES预处理脂肪肝移植组肝细胞损伤程度明显减轻 ,线粒体UCP 2水平低于脂肪肝移植组。结论　维生素E酯预处理对小鼠脂肪肝移植有一定保护作用。     

肝移植后因药物不良反应暂停及转换钙调磷酸酶抑制剂的单中心经验

目的 研究肝移植术后暂停及转换钙调磷酸酶抑制剂(CNI)对控制感染和改善受损肾功能的作用.方法 回顾性分析单中心施行的947例原位肝移植的资料,分为2个阶段,第1阶段(2002年1月至2007年12月)有234例肝移植术后发生感染的患者,第2阶段(2008年1月至2010年12月)有101例.2个阶段共有329例受者因CNI肾毒性而造成肾功能损害,其中将CNI转换为SRL者40例(转换组),其余289例采取CNI减量+吗替麦考酚酯(MMF)加量方案(减量组).结果 肝移植术后存活超过1、3和5年者CNI的应用率分别为95.8%、95.3%和97.5%.第2阶段共有17例受者短期停用免疫抑制剂,停药的主要原因是细菌(部分合并真菌)感染(88.2%);2个阶段共有48例患者将CNI转换为SRL,换药主要原因是肾功能损害(83.3%).第2阶段感染患者中短期暂停CNI者15例,占14.9%(15/101),CNI暂停后感染控制的有效率为73.3%(11/15),排斥反应发生率为6.7%(1/15).第2阶段感染患者的累积存活率明显高于第1阶段(P＜0.05).转换组CNI转换前肾小球滤过率为(0.82±0.24)ml/s,CNI转换后6周时为(1.28±0.31)ml/s,6个月时为(1.36±0.32)ml/s,转换后6周和6个月时高于转换前(P＜0.05).CNI调整后6个月时,转换组患者存活率为85.0%,减量组为83.7%(P＞0.05).结论 肝移植术后患者发生感染及肾功能损害时可采取CNI减量甚至短时间停用CNI,或转换使用SRL,此方案是安全、有效的.

Abstract：

Objective To report the results of a single-center, retrospective study on the effect of calcineurin inhibitors (CNI) withdraw for controlling infections and conversion to sirolimus (SRL)for ameliorating renal dysfunction. Methods A total of 947 liver transplant cases from 2002 to 2010were divided into two eras (Jan. 2002 to Dec. 2007 and Jan. 2008 to Dec. 2010). There were 234cases of infections after liver transplantation (LT) in the first era and 101 cases in the second era. And of 329 cases of CNI-related renal dysfunction after LT in two eras, 40 cases (converting group) had converted CNI to SRL, while 289 cases (reducing group) adopted protocol of CNI reducing and mycophenolate mofetil (MMF) raising. Results CNI-based IS took up 95.8 %, 95. 3 %, 97. 5 % of the IS protocols with recipient survival time longer than 1, 3, and 5 years. The primary cause for CNI withdraw was infection (88. 2 %, 15/17) in the second era, and renal dysfunction for conversion to SRL in the two eras (83. 3 %, 40/48). In the second era, 14. 9% (15/101) of the cases of infections after LT experienced CNI withdraw. Of the 15 patients, 11 had effectively controlled the infection (77. 3 %) while rejection rate was 6. 7 % (1/15). The cumulative survival rate of the second era was significantly higher than the first era (P＜0. 05). The glomerular filtration rate (GFR) of converting group at 6th week and 6th month was statistically elevated as compared with that before conversion,respectively (1.28 ± 0. 31, 1.36 ± 0. 32 mL/s vs. 0. 82 ± 0. 24 mL/s, P＜0. 05). Six months after CNI adjustments, survival rate of converting group and reducing group was 85. 0% and 83. 7 %,respectively (P＞0. 05). Conclusion Reducing or even short-term withdraw of CNI may allow the better control of infections after LT, and the conversion from CNI to SRL can ameliorate the CNIrelated nephrotoxicity. These individually tailored IS protocols will benefit the long term survival for LT.     

一剂赛尼哌对肾移植急性排斥反应的预防作用

目的 探讨1剂赛尼哌在预防同种异体肾移植急性排斥反应中的作用。方法 回顾性分析50例应用1剂赛尼哌的肾移植患者资料，同期30例未应用赛尼哌患者作为对照，随访6个月。分析比较2组患者急性排斥反应、移植肾功能、感染及赛尼哌不良反应发生情况。结果 赛尼哌组发生急性排斥反应13例（26％），对照组为17例（57％），差异有统计学意义（P〈0．05），2组患者药物不良作用方面、血液系统损害、肝功能损害、感染发生率及人／肾存活率差异无统计学意义（P〉0．05）。结论 联合应用1剂赛尼哌免疫抑制方案可以降低肾移植急性排斥反应发生率，改善移植肾功能，不良反应轻。     

Wilson''''s病患者亲体部分肝移植和全肝移植术后血清铜蓝蛋白及尿铜水平的变化

目的　总结Wilson’s病患者亲体肝移植和全肝移植术后血清铜蓝蛋白及尿铜水平的恢复情况。方法　自 2 0 0 0年 9月至 2 0 0 3年 11月我院为 2 6例Wilson’s病患者施行了肝移植术 ,均并发终末期肝硬变 ,其中 3例发生急性肝功能衰竭。术前血清铜蓝蛋白和尿铜水平分别为 (12 4 .8± 2 2 .8)mg/L和 (15 2 4 .8± 32 8.6 ) μg/ 2 4h ,其中行活体部分肝移植 2 2例 ,全肝移植 4例 ,亲体肝移植供体术前血清铜蓝蛋白水平为 (2 30 .4± 2 9.6 )mg/L ,尿铜水平均 <5 0μg/ 2 4h。结果　所有患者手术顺利 ,全肝移植患者术后 1、3、6及 12个月血清铜蓝蛋白和尿铜水平分别为 (32 0 .2±36 .8)mg/L、(380 .4± 4 5 .6 )mg/L、(36 0 .5± 37.6 )mg/L、(35 6 .2± 2 7.6 )mg/L和 (2 4 0 .4± 2 2 .8) μg/ 2 4h、(86 .5± 10 .6 ) μg/ 2 4h、(5 4 .2± 6 .8) μg/ 2 4h及 (46 .8± 3.4 ) μg/ 2 4h ;亲体肝移植患者术后 1、3、6及 12个月血清铜蓝蛋白和尿铜水平分别为 (2 16 .8± 2 0 .4 )mg/L、(2 4 8.5± 32 .6 )mg/L、(2 85 .4± 4 4 .3)mg/L、(2 6 0 .2± 36 .6 )mg/L和(380 .8± 37.6 ) μg/ 2 4h、(15 0 .6± 2 4 .5 ) μg/ 2 4h、(75 .5± 9.6 ) μg/ 2 4h及 (6 0 .3± 5 .8) μg/ 2 4h。结论　全肝移植和亲体肝     

经皮肾输尿管镜碎石取石术联合ESWL治疗肾功能不全的孤立肾鹿角形结石

目的探讨经皮肾输尿管镜碎石取石术联合ESWL治疗肾功能不全的孤立肾鹿角形结石的疗效. 方法经皮肾穿刺微造瘘延期输尿管镜下碎石取石术(minimally invasive percutaneous nephrolithotomy,MPCNL)联合体外冲击波碎石(extracorporeal shock wave lithotripsy,ESWL)治疗肾功能不全的孤立肾鹿角形结石8例. 结果 5例取尽结石,3例残余结石.术中未输血,未出现严重手术并发症.术后肾功能有不同程度的改善,血Cr由术前(289±166)μmol/L降至(155±33)μmol/L (t=4.69,P=0.004),血BUN由术前(15.1±7.9) mmol/L降至(8.3±1.9)mmol/L(t=4.00,P=0.005) ,ECT检查GFR由术前(48.8±12.4) ml/s升高至(63.0±8.4)ml/s(t=4.68,P=0.003).术后肾后性梗阻消失.8例随访0.5～4.5 年,平均2.8年,肾功能较术后无明显变化. 结论 MPCNL结合ESWL治疗肾功能不全的孤立肾鹿角形结石安全、疗效好.     

巴利昔单克隆抗体在肝移植中应用的早期观察

目的观察巴利昔单克隆抗体(单抗)在肝移植早期应用的安全性和有效性。方法将2003年11月至2004年11月间首次肝移植的40例患者随机平均分为实验组和对照组。实验组患者于术中下腔静脉开放时和术后第4d各接受20mg(总剂量40mg)巴利昔单抗诱导治疗。两组的围手术期均以钙调神经磷酸酶抑制剂(CNI) 霉酚酸酯(MMF) 皮质激素预防排斥反应。观察两组患者术后30d内的急性排斥反应和感染发生率以及血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)、总胆红素(TB)和直接胆红素(DB)水平。结果肝移植术后30d内,实验组和对照组的急性排斥反应发生率分别为10%(2/20)和45%(9/20),两组比较,P=0.034;感染发生率分别为40%(8/20)和45%(9/20),两组比较,P=0.749。ALT、AST、TB、DB逐步下降,且实验组下降更明显,两组在术后第7d、14d差异有显著性;而ALP逐步上升,第21d左右达峰值。结论肝移植术后早期,在常规三联免疫抑制方案基础上加用巴利昔单抗是安全的,能够减低急性排斥反应发生率,但长期疗效仍在进一步观察中。     

抗CD25抗体在致敏受者肾脏移植免疫诱导治疗中的临床观察

目的　评价致敏受者肾脏移植应用抗CD2 5抗体 (赛尼哌 )作为免疫诱导治疗的有效性和安全性。方法　将 36例接受肾移植的致敏受者随机分为两组 ,赛尼哌组 18例 ,OKT3组 18例。所有患者免疫抑制维持治疗为他克莫司 (FK5 0 6 )或环孢素A(CsA) +霉酚酸酯 (MMF) +泼尼松(Pred)三联疗法。赛尼哌组 :分别在术前 2 4h和术后 14d静脉内输入 5 0mg赛尼哌 ;OKT3组 :术后第 1d开始应用OKT3,每天 5mg ,持续 5～ 10d。观察两组术后半年内急性排斥 (AR)、移植肾功能延迟恢复 (DGF)的发生情况。结果　有 7例患者术后发生AR ,其中赛尼哌组 4例 ,OKT3组 3例。有13例发生DGF ,其中赛尼哌组 4例 ,OKT3组 9例 (P <0 .0 1)。在过敏反应、细胞因子释放综合征、神经系统症状、感染等方面 ,赛尼哌组发生率明显低于OKT3组 (P <0 .0 5 )。结论　赛尼哌是一种强效安全的免疫抑制剂 ,在致敏受者肾移植的免疫诱导治疗中效果满意。     

肝移植后并发他克莫司不良反应者的西罗莫司单药转换治疗14例

目的 总结出现钙调磷酸酶抑制剂(CNI)相关并发症的患者采用西罗莫司(SRL)单药转换治疗的体会.方法 肝移植患者14例,其中因CNI类药物致肾功能受损而行转换治疗者13例,因移植后血糖升高而行转换治疗者1例.转换治疗前,患者采用他克莫司(Tac)和糖皮质激素预防排斥反应,部分患者还加用霉酚酸酯.进行转换治疗后,初次给予SRL 4 mg/d;1周内给予SRL 1～2 mg/d,同时Tac的用量减至原来的一半;治疗1周后,根据血SRL浓度调整其剂量,维持血SRL浓度谷值为5～10μg/L,于转换治疗后1～2周完全撤除Tac.观察患者转换治疗后并发症的改善情况,肾功能、肝功能和急性排斥反应的发生情况及药物不良反应等.结果 转换治疗前,13例肾功能受损者的血肌酐为(158.3±41.6)μmol/L,随访结束时降低到(103.7±21.2)μmol/L;另1例血糖升高者在转换治疗后血糖得到有效控制,胰岛素用量由转换前的80 IU/L减少至24 IU/L.转换治疗后6个月内,14例中有2例(14.3%)发生急性排斥反应,治疗后均逆转.随访过程中,4例出现血脂升高,4例出现贫血或血小板减少,5例出现溃疡型口疮,但无患者因SRL不良反应而终止转换治疗.结论 肝移植术后出现CNI相关并发症的患者可以采用SRL单药转换治疗.     

慢性肾功能损伤的肝移植受者转换为西罗莫司治疗的疗效观察

目的 观察慢性肾功能损伤的肝移植受者转换为西罗莫司治疗的疗效.方法 应用钙调磷酸酶抑制剂(CNI)并伴有慢性肾功能损伤的肝移植受者23例(其中19例应用他克莫司,4例应用环孢素A)转换为西罗莫司(SRL)治疗.SRL的起始剂量为4mg/d,次日为2 mg/d,应用高压液相色谱法测定全血SRL浓度,当血SRL浓度达5～8 μg/L后,停用CNI类药物,同时服用吗替麦考酚酯,1 g/d.记录受者入组前的基础血清肌酐(Cr)、肌酐清除率、肾小球滤过率(GFR),并分别于用药后第1、3、6、12和24个月时监测血SRL浓度、Cr、肌酐清除率、GFR,同时监测受者体重、血压、血细胞计数、肝功能和肝脏生化指标、血脂、尿蛋白.于用药后12个月时行肝脏穿刺活检确认有无排斥反应.结果 23例平均随访29.4个月,随访期内死亡2例,另21例于用药后1、3、6、12和24月时的Cr分别为(147.40±23.36)、(152.60±20.08)、(150.20±22.64)、(137.60±18.09)、(138.30±17.04)μmol/L,与Cr的基础值[(158.91±29.13)μmol/L]相比较,1、12、24个月时的差异有统计学意义(P＜0.05).用药后1、3、6、12和24月时的肌酐清除率分别为(0.97±0.18)、(0.99±0.14)、(1.00±0.17)、(1.07±0.29)、(1.14±0.12)ml/s,与基础肌酐清除率[(0.91±0.14)ml/s]相比较,1、12、24个月时的差异有统计学意义(P＜0.05).用药后1、3、6、12和24月时的GFR分别为(0.80±0.15)、(0.78±0.11)、(0.75±0.12)、(0.84±0.10)、(0.94±0.13),与基础GFR[(0.71±0.11)ml/s]相比较,1、12、24个月时的差异有统计学意义(P＜0.05).应用SRL后第1、3、6、12和24个月时,Cr≤123μmol/L者所占的比例分别为38.1％、33.3％、28.6％、47.6％和52.4％.随访期内无受者发生排斥反应.结论 慢性肾功能损伤的肝移植受者转换为西罗莫司治疗可改善其肾功能.转换治疗未增加排斥反应的发生率.     

The safety and efficacy of a two-dose daclizumab (zenapax) induction therapy in liver transplant recipients

BACKGROUND: Induction therapy with daclizumab has been shown to be efficacious in the prevention of acute rejection in kidney transplant patients. The routine use of antibody induction therapy in liver transplantation has not gained widespread acceptance, except in the cases of renal insufficiency. The recent approval of daclizumab prompted us to initiate this pilot study using induction therapy in those patients at risk for developing posttransplant renal insufficiency. METHODS: This nonrandomized study examined the use of daclizumab in 39 of the last 97 liver transplants performed at the University of Alabama in Birmingham. The daclizumab group received 2 mg/kg intravenously before organ engraftment, and 38 of the 39 received 1 mg/kg intravenously on postoperative day 5. The control group consisted of the remaining 58 contemporary patients. Additional immunosuppression consisted of steroids, tacrolimus, or microemulsion cyclosporine in all patients and mycophenolate mofetil in selected patients. RESULTS: Pretransplant demographics were not significantly different between the groups. In the induction group there were significantly fewer males, 14 (36%) vs. 34 (59%) (P=0.03). They had greater renal insufficiency at the time of transplant, serum creatine 1.9+/-0.37 mg/dl vs. 0.8+/-0.5; P=0.0009, and more patients were at higher acuity (status 1 and 2A): 12 (31%) vs. 3 (5%) P=0.0006 than in the noninduction group. By postoperative day 7, renal function improved in the induction group such that it was not significantly different from the noninduction group and remained similar throughout the rest of the follow-up. The induction group also experienced significantly less acute rejection, 7 (18%) vs. 23 (40%) (P=0.02) than in the noninduction group in the first 6 months. The 1-, 3-, and 6-month patient survival rates were similar in the induction group, 97.4%, 97.4%, and 97.4%, vs. non-induction 94.8%, 93.0%, and 93% (P=NS). The incidence of cytomegalovirus, in the first 6 months, in the induction group was four (10%) vs. five (9%) (P=NS) in the noninduction group. CONCLUSION: In the pilot study, induction therapy with daclizumab was safe, facilitated improvement in renal function, and appeared to reduce the incidence of acute rejection. Combination therapy with daclizumab may be an important adjunct in immunosuppressive strategies for liver transplant recipients.     

Pediatric liver transplantation with daclizumab induction

BACKGROUND: A new class of monoclonal antibodies (non-T-cell depleting) has gained favor for induction therapy after transplantation. This study evaluated the non-T-cell depleting antibody to the CD25 cell, daclizumab, as a single-dose induction agent immediately after pediatric liver transplantation to spare the use of the calcineurin inhibitor, tacrolimus, for 7 days in respect to both efficacy and renal function. METHODS: From January 1998 to November 2001, 81 pediatric orthotopic liver transplant recipients receiving 89 liver grafts were evaluated. The treatment arm (n=61) received daclizumab 1 mg/kg immediately after liver transplantation along with mycophenolate, steroids, and, on postoperative day 7, tacrolimus. The control group did not receive induction therapy, whereas tacrolimus, mycophenolate, and steroids were started immediately after surgery. RESULTS: The induction group had fewer patients with rejection within the first 30 days after liver transplantation (9 [14.8%] vs. 10 [50%]; P=0.003). The mean time to first rejection was similar between groups (12.1 [+/-7.8] days vs. 18.5 [+/-8.1] days; P=not significant). There was a 3.39 increase in relative risk to develop rejection within the first 30 days after orthotopic liver transplantation if the patient did not receive induction therapy (relative risk=3.39; 95% confidence interval [1.61, 7.14]). Two-year actuarial survival for the induction group was 93.2% compared with 85% in the control; graft survival was also similar between groups (87.8% vs. 72.7%) at 2 years. CONCLUSION: Daclizumab 1 mg/kg given immediately after pediatric liver transplantation and withholding tacrolimus, is safe, efficacious, and reduces rejections within the first 30 days after surgery.     

Experience with daclizumab in liver transplantation: renal transplant dosing without calcineurin inhibitors is insufficient to prevent acute rejection in liver transplantation

BACKGROUND: Daclizumab is a monoclonal antibody directed against the alpha chain of the interleukin 2 receptor. We review our experience with the use of daclizumab in liver transplant recipients. METHODS: Thirty-two patients were given daclizumab as induction therapy in the setting of hepatic transplantation. Seven of these patients were enrolled in a pilot study to determine the efficacy of daclizumab in conjunction with corticosteroids and mycophenolate mofetil without the initial use of calcineurin inhibitors (CI). The remaining 25 patients received daclizumab, mycophenolate mofetil, and steroids, with the institution of CI generally within the first postoperative week. The majority of these patients (n = 17) had some degree of renal insufficiency. RESULTS: The pilot study was halted after the first seven patients were enrolled because of an unacceptably high rate of rejection (7/7 = 100%). The patients outside of this pilot study, however, had a much lower rate of rejection (36%). The incidence and severity of rejection correlated with the delay in institution of CI. The described dosing schedule resulted in subtherapeutic daclizumab levels in liver transplant recipients. CONCLUSIONS: Daclizumab used in liver transplant recipients without any CI was ineffective and can potentially lead to steroid-resistant rejection. The dosing regimen used in renal transplant recipients is most likely insufficient for liver transplant patients. However, daclizumab can be used safely in patients with preexisting or postoperative renal dysfunction in conjunction with low doses of CI given within the first week postoperatively.     

Renal function after orthotopic liver transplantation is predicted by duration of pretransplantation creatinine elevation.

In patients with recent onset renal insufficiency, the decision to perform combined kidney/liver transplantation (CKLT) vs. orthotopic liver transplantation alone (OLTa) can be difficult. We hypothesized that duration of renal dysfunction may correlate with creatinine elevation after liver transplantation. We retrospectively identified 69 liver transplantation patients with pretransplantation creatinine > or =1.5 mg/dL (53 OLTa, 13 CKLT). Variables analyzed were presence of hepatorenal syndrome, creatinine, Model for End-Stage Liver Disease score, albumin, age, race, gender, cause of liver disease, diabetes mellitus, hypertension, and history of ascites, spontaneous bacterial peritonitis, variceal bleeding, hepatic encephalopathy, renal replacement therapy (RRT), and transjugular intrahepatic portosystemic shunting. Duration of pretransplantation renal dysfunction was predictive of 6- and 12-month creatinine post-OLTa. Area under the receiver operating characteristic (ROC) curve for prediction of 12-month renal insufficiency by renal dysfunction duration was 0.71; optimal duration cutoff was 3.6 weeks. We applied a multivariable model, derived from OLTa patients, to CKLT subjects with definite or possible hepatorenal syndrome. Predicted 12-month creatinine without renal transplantation was >2.0 mg/dL for each patient. CKLT patients as opposed to OLTa patients had longer duration of renal dysfunction (median, 18.1 vs. 2.7 weeks, P < 0.001), higher creatinine (median 4.0 versus 1.7 mg/dL, P < 0.001), and higher rate of pretransplantation RRT (62% vs. 7%, P < 0.001). Adjusting for baseline characteristics, CKLT patients had lower creatinine than OLTa patients at 6 months (P =0.15) and 12 months (P =0.01) after transplantation. In conclusion, duration, but not cause, of renal dysfunction predicts renal outcome in OLTa recipients. Prospective studies may use duration of renal dysfunction to help identify CKLT candidates.     

Evaluation of renal function in liver transplant recipients receiving daclizumab (Zenapax), mycophenolate mofetil, and a delayed, low-dose tacrolimus regimen vs. a standard-dose tacrolimus and mycophenolate mofetil regimen: a multicenter randomized clinical trial.

Posttransplant chronic renal failure, secondary to calcineurin inhibitor agents, is emerging as a major problem in liver transplantation. We report a randomized clinical trial comparing daclizumab, delayed low-dose tacrolimus (target trough level 4-8 ng/mL, starting day 4-6), Investigational Arm (n = 72), to standard tacrolimus induction/maintenance dosing, Standard Arm (n = 76), with mycophenolate mofetil and tapering corticosteroids in both study arms. The end-points were renal function indicated by the Modification of Diet in Renal Disease (MDRD). There was no significant difference in patient survival (86.6% Investigational Arm vs. 92.9% Standard Arm; P = 0.21) or acute rejection (23.2% vs. 27.7%, respectively; P = 0.68). Statistically significant differences in median glomerular filtration rate (GFR) were found in favor of the Investigational Arm. With the CG equation, the GFR at the end of the first week was 110.7 vs. 89.6 mL/min (P = 0.019) without significant differences thereafter. With the MDRD, statistically significant differences extended to the first posttransplant month (86.8 vs. 70.1 mL/min/1.73 m(2); P < 0.001) with and was seen at month 6 (75.4 vs. 69.5 mL/min/1.73 m(2); P = 0.038). In conclusion, delayed low-dose tacrolimus, in combination with daclizumab and mycophenolate mofetil, preserves early renal function post-liver transplantation without the cost of increased acute rejection.     

The course of type 1 hepato-renal syndrome post liver transplantation.

BACKGROUND: Hepato-renal syndrome (HRS) is a functional form of renal failure that occurs in patients with end-stage liver disease. Previously considered fatal without liver transplantation, treatment with vasoconstrictors and albumin has been demonstrated to improve renal function in patients with type 1 HRS. Liver transplantation is still considered the definitive treatment for HRS. However, the renal recovery rate and those factors that predict recovery post orthotopic liver transplantation have not been determined. METHODS: We reviewed the hospital course of 28 patients who met the International Ascites Club criteria for type I HRS and who underwent orthotopic liver transplant. The patients' demographic and pre- and post-operative laboratory data were recorded; patients were followed for 4 months post-transplantation or until death. RESULTS: The MELD score of the patients was 30+/-6. The mean duration of HRS prior to liver transplantation was 37+/-27 days. HRS resolved in 16 patients (58%). The mean time to resolution of HRS was 21+/-27 days, with a range of 4-110 days. Eight (50%) patients in whom the HRS resolved were undergoing pre-transplantation dialysis. The age of the recipients (49+/-10 vs 56+/-12; P = 0.05), the total bilirubin level on post-operative day 7 (6.0+/-4.3 vs 10.1+/-5.9 mg/dl; P = 0.04), alcoholic liver disease and the requirement for post-transplant dialysis were predictors of resolution of HRS by univariate analysis. Only alcoholic liver disease and post-transplant dialysis were independent (negative) predictors of resolution of HRS. Seven of the 12 (58%) patients who developed chronic renal insufficiency remained dialysis dependent. The pre-operative serum creatinine was non-significantly higher in the non-resolvers who remained dialysis dependent compared to those who did not require long-term dialysis (3.0+/-1.0 vs 2.3+/-0.4 mg/dl; P = 0.1) Four patients died; in three of these patients the HRS had resolved prior to their death. CONCLUSION: HRS is not always cured by orthotopic liver transplant. Pre-transplantation dialysis or a long waiting period should not preclude transplantation in patients with HRS. HRS may not resolve in patients with alcoholic liver disease. We were unable to accurately define that group of patients with HRS who required long-term dialysis and could theoretically benefit from combined liver-kidney transplantation.     

Two-dose daclizumab induction therapy in 209 liver transplants: a single-center analysis

BACKGROUND: Patient and graft survival after liver transplantation are adversely affected by early posttransplant renal dysfunction. Therefore, our immunosuppressive strategies should be as "renal sparing" as possible. This is the largest published series to date using daclizumab induction therapy in a renal-sparing regimen. METHODS: This is a retrospective, nonrandomized study comparing 209 adult liver transplants with daclizumab induction to 115 transplants with no induction. RESULTS: Patient and graft survival were similar, despite higher pretransplant acuity of illness and older age in the induction group. Acute rejection within the first 6 months occurred less commonly in the induction group (25.4% vs. 39.1%, P=0.01), despite significantly delayed initiation and lower doses of a calcineurin inhibitor. Mycophenolate mofetil was used more commonly in induction patients, but the efficacy of daclizumab in preventing rejection was independent of this. Patients with a pretransplant creatinine concentration 1.5 mg/dL or less had less rejection if they received induction. Renal function worsened in noninduction patients but showed sustained improvement throughout follow-up in induction patients with a pretransplant creatinine concentration greater than 1.5 mg/dL. Induction therapy provided better rejection prophylaxis among those requiring temporary calcineurin inhibitor cessation because of renal dysfunction. The incidences of histologic hepatitis C recurrence and cytomegalovirus infection were similar in each group. CONCLUSIONS: Liver recipients with and without pretransplant renal dysfunction have less acute rejection with daclizumab induction therapy. This is not associated with an increased risk of over-immunosuppression. Sustained renal improvement in recipients with pretransplant renal dysfunction is possible with daclizumab induction.     

Daclizumab (humanized anti-IL2Ralpha mAb) prophylaxis for prevention of acute rejection in renal transplant recipients with delayed graft function.

BACKGROUND: The purpose of this retrospective study was to determine the benefits of daclizumab, (Zenapax, Roche Pharmaceuticals) a humanized anti-interleukin-2Ralpha (IL-2Ralpha) monoclonal antibody, for prevention of acute rejection in renal transplant recipients with delayed graft function (DGF). METHODS: Data from two multicenter randomized placebo-controlled trials were pooled. DGF was defined by urine output <30 cc/hour, decline in serum creatinine of <0.5 mg/dl, or the need for dialysis within the first 24 hours after transplantation. RESULTS: At one year posttransplantation, the incidence of biopsy-proven acute rejection in patients with DGF was reduced from 44% in the placebo group to 28% in the daclizumab group. (P=0.03) Prophylaxis with daclizumab also delayed the onset of the first biopsy-proven acute rejection episode in patients with DGF from 29+/-43 days in the placebo group to 73+/-70 days in the daclizumab group. (P=0.004) The graft survival rates in patients with DGF at 1 year posttransplantation were 78% in the placebo group and 82% in the daclizumab treated group. (P=ns) Three patients in the placebo-treated group with DGF experienced graft loss due to acute rejection, whereas no patients in the daclizumab-treated group with DGF had graft loss due to acute rejection. The 1-year patient survival rate in those with DGF in the placebo and daclizumab groups were 93% and 98%, respectively. (P=ns) CONCLUSIONS: Daclizumab effectively reduced the incidence and delayed the onset of biopsy-proven acute rejection in this high-risk subgroup of patients with DGF after renal transplantation. Graft and patient survival rates were similar between placebo- and daclizumab-treated patients with DGF.     

Influence of hepatitis C on renal function after liver transplantation

Liver transplantation (OLT) is often complicated by renal failure. Hepatitis C (HCV) is said to be a risk factor for renal failure after OLT, but few studies have analyzed this directly. We evaluated all patients who received a liver transplant from 1995 through 2003. There were 147 patients infected with HCV and 202 not infected. Patients with HCV were further divided into 114 patients with benign HCV and 33 patients with severe HCV defined by bridging fibrosis or cirrhosis. The groups were evaluated for the development of renal insufficiency defined as a creatinine above 1.8 mg/dL on three consecutive occasions or renal failure as defined by the need for dialysis or renal transplant. The incidence of renal failure in patients with HCV was 10.2% and in patients without HCV was 3.5% (P = .004). Patients with severe HCV had an incidence of 12.1% vs 9.7% for patients with mild HCV. The linear trend in renal failure from non-HCV to mild HCV to severe HCV was significant (P = .012). The incidence of renal insufficiency was 23.4% in patients with HCV and 14.9% in patients without HCV (P = .080). The incidence was 32.3% in patients with severe HCV and 20.6% in patients with mild HCV. The trend in renal insufficiency across the three groups was mildly significant (P = .042). On multivariate analysis, HCV was a risk factor for renal failure with a relative risk of 2.58 (P = .045). The study suggests that HCV and the severity of recurrent HCV are risk factors for renal dysfunction after liver transplantation.     

Daclizumab induction, tacrolimus, mycophenolate mofetil and steroids as an immunosuppression regimen for primary kidney transplant recipients

BACKGROUND: Recent reports have demonstrated the efficacy of interleukin-2-receptor blockers in lowering the incidence of early acute rejection in cyclosporine-treated kidney recipients when compared to patients not induced with an antibody product. The addition of daclizumab to a tacrolimus-mycophenolate mofetil-based immunosuppressive protocol was tested to evaluate whether there might be an additional reduction of the risk of rejection after renal transplantation. METHODS: Since March 1998, we studied the effect of daclizumab in a nonrandomized, prospective study of 233 sequential recipients of first renal transplant. They were retrospective compared with a control group of 225 renal transplant recipients receiving a 10-day course of OKT3 induction, and tacrolimus, mycophenolate mofetil, and methylprednisolone maintenance. The study group received the same immunosuppressive regimen with the addition of daclizumab at 1 mg/kg for five doses over 10 weeks in the place of OKT3 therapy. There was at least 1HLA DR antigen compatibility match present between all donors and recipients. Patients were followed for 1 year after renal transplantation for the incidence of biopsy-proven acute rejection, patient and graft survival, and adverse events. RESULTS: At 12 months, patient and graft survival for the daclizumab was 98 and 96 vs. 96 and 94% for the OKT3 group, respectively, and were not statistically different. Acute rejection rates (<6 months) were lower in the daclizumab group as compared with the OKT3 group, i.e., 5 (2.1%) vs. 16 (7.1%) (P=0.011) respectively. The incidence of infection requiring hospitalization appeared to be lower with daclizumab (7.3 vs. 16%, P<0.0036) with a similar trend with cyclomegalovirus infection, i.e., 1.6 vs. 4%, respectively (P=0.14). CONCLUSIONS: The combination of daclizumab, tacrolimus, mycophenolate mofetil, and steroids is safe and effective for kidney transplant recipients in lowering the incidence of early acute rejection and without any increase in morbidity when compared to our previous protocol, which may have an eventual impact in long-term graft survival.