肝细胞癌肝移植适应证选择的疗效评估

目的:总结肝癌肝移植不同标准适应证的疗效,探讨影响预后的因素.方法:回顾性分析2002年6月至2007年6月96例肝细胞癌肝移植病例,其中符合米兰(Milan)标准者29例,符合加利福尼亚(UCSF)标准者41例,超过UCSF标准者55例.采用Kaplan-Meier法统计分析不同病例入选标准对肝癌肝移植术后生存率及无瘤生存率的影响,并进行Log-rank和Cox多元回归分析.结果:Milan和UCSF标准内影响长期生存的因素包括肿瘤分化、肿瘤部位、镜下癌栓和TNM分期.Milan标准组术后1、2、3、4年总体生存率分别为92.5%、79.6%、79.6%及53.0%,无瘤生存率分别为90.2%、79.3%、76.3%及51.7%;UCSF标准组术后1、2、3、4年总体生存率分别为92.4%、80.9%、73.0及51.1%,无瘤生存率分别为90.2%、79.8%、71.7%及50.2%;超过UCSF标准组术后1、2、3、4年总体生存率分别为66.3%、39.8%、26.5%及15.9%,无瘤生存率分别为64.4%、31.5%、15.8%及15.8%.Milan、UCSF标准组生存率和无瘤生存率与超过UCSF标准组比较有显著差异(P<0.01),Milan标准组与UCSF标准组间生存率和无瘤生存率无显著差异(P>0.05).结论:与Milan标准相比,UCSF标准显著扩大了肝癌肝移植的适应证范围,更符合作为选择肝癌肝移植病人的标准.     

依维莫司在肝细胞癌肝移植术后的临床应用

目的阐述依维莫司(everolimus,EVR)的作用机制以及EVR在肝细胞癌(hepatocellular carcinoma,HCC)患者肝移植术后的应用和疗效及常见不良反应。方法通过万方、知网、PubMed等网站检索近年来的相关文献,进行阅读、分析、总结,得出结论。结果目前用于HCC患者肝移植术后的免疫抑制剂种类众多,免疫抑制治疗方案也多种多样且尚无统一标准。现今临床上使用较为广泛的用于移植术后的免疫抑制剂为钙调磷酸酶抑制剂(calcineurin inhibitors,CNIs),但由于其肾毒性及增加HCC复发概率等副作用,CNIs在HCC患者肝移植术后的使用逐渐受到限制,而哺乳动物雷帕霉素靶点(mammalian target of rapamycin,mTOR)抑制剂则开始受到重视,逐步走入临床,为肝移植术后免疫抑制治疗提供了新思路。EVR作为一种mTOR抑制剂,正逐步应用于HCC患者肝移植术后。结论 EVR作为近年来才被批准使用于HCC患者肝移植术后的mTOR抑制剂,相关文献研究均显示它在提高移植成功率、对肾功能的保护及抑制HCC复发等方面发挥了重要作用。     

不同移植标准下挽救性肝移植的疗效对比分析

目的分析比较符合米兰标准、UCSF标准、杭州标准的肝细胞肝癌(hepatocellular carcinoma, HCC)切除术后肿瘤复发患者肝移植术后的预后情况。方法回顾性分析2015年1月至2019年10月在复旦大学附属华山医院行公民逝世后器官捐献(donation after citizen death, DCD)肝移植的256例HCC患者的临床资料。其中, 行初期肝移植175例(PLT组), 挽救性肝移植81例(SLT组)。采用t检验、秩和检验或χ2检验比较两组受者的一般资料、肿瘤病理特征、术后并发症等, 用Kaplan-Meier法和Log-rank检验比较两组受者的术后总生存率(overall survival rate, OS)和无复发生存率(recurrence-free survival rate, RFS)。SLT组符合米兰标准者31例(米兰标准组)、符合加州大学旧金山分校(UCSF)标准者45例(UCSF标准组)、符合杭州标准者69例(杭州标准组), 比较三组受者的OS和RFS。按肝移植术前是否接受降期/桥接治疗, 将SLT组受者再分为降期治疗组(32例)和未降期...     

西罗莫司应用于肝癌肝移植受者的疗效分析

目的 评估肝癌肝移植受者应用西罗莫司对肿瘤复发和受者存活的影响.方法 回顾性分析2006年1月至2011年1月行肝癌肝移植的142例受者的资料,根据术后是否应用西罗莫司分为研究组(62例)和对照组(80例).采用生存分析方法比较两组患者的无瘤生存时间、带瘤生存时间及受者对西罗莫司的耐受性.结果 两组受者无瘤生存率的差异无统计学意义(P＞0.05).两组符合米兰标准者、超过米兰标准且符合美国加州大学旧金山分校(UCSF)标准者、超过UCSF标准者分别相比较,受者无瘤生存率的差异无统计学意义(P＞0.05).对照组中有35例肝移植后肿瘤复发,其中21例肿瘤复发后加用西罗莫司,带瘤生存时间中位数为12个月;14例复发后继续使用原有免疫抑制剂,带瘤生存时间中位数为8个月;两者带瘤生存时间的差异有统计学意义(P=0.039).研究组新发糖尿病发生率低于对照组,但是口腔溃疡和高脂血症发生率却高于对照组,差异均有统计学意义(P＜0.05).结论 未发现西罗莫司能明显降低肝癌肝移植后肿瘤复发率,但移植后肿瘤复发者应用西罗莫司可延长其带瘤生存时间;应用西罗莫司者移植后糖尿病的发生率较低.     

肝细胞癌肝移植术后长期生存率的影响因素

为研究肝细胞癌原位肝移植术后生存率和无瘤生存率的影响因素,作者收集了1989·1~2005·11意大利Niguarda医院的155例肝细胞癌肝移植病例进行分析。其中116例术前诊断为肝细胞癌,39例肝移植术后病理诊断为肝细胞癌,84%的病例术前符合“米兰”标准,94例病例术前进行了抗肿瘤治疗     

超“UCSF标准”肝细胞癌肝移植术前经肝动脉化疗栓塞的疗效

目的:评估经肝动脉化疗栓塞(TACE)在超"UCSF标准"肝细胞癌(HCC)肝移植术前治疗的安全性及疗效。方法:回顾性分析2003年1月至2013年3月在本院行肝移植治疗的83例超"UCSF标准"的成年HCC病人临床资料,根据术前是否采取TACE治疗分为TACE治疗组(63例)与对照组(20例)。比较两组病人术后急性排异、胆道并发症和血管并发症发生率、无瘤生存率及总生存率。结果:TACE治疗组在肝移植术前平均进行了(2.0±1.3)次TACE疗程,末次治疗至肝移植的平均时间为(15.7±8.4)d。TACE治疗组与对照组相比,在肝移植术后急性排异、肝动脉栓塞和胆道并发症发生率差异无统计学意义(P0.05)。TACE治疗组无瘤生存率及总生存率明显优于对照组(P0.05)。分层分析表明,TACE治疗后获得完全反应或部分反应的HCC病人行肝移植1、3、5年无瘤生存率及总生存率明显高于TACE治疗后无反应组(P0.05)。TACE治疗后肿瘤降期至"UCSF标准"的HCC病人行肝移植1、3、5年无瘤生存率及总生存率明显高于降期治疗后未达到"UCSF标准"的病人(P0.05)。结论:肝移植术前TACE治疗可延长病人无瘤生存及总生存时间。肝移植术前TACE降期治疗安全,仅1例发生肝动脉栓塞并发症。     

不同肝癌肝移植标准受者预后分析

目的分析不同肝癌肝移植标准受者预后情况，评价不同标准之间的差异。 方法回顾性分析2013年1月至2017年12月首都医科大学附属北京朝阳医院原发性肝癌肝移植受者的临床资料，比较不同肝癌肝移植标准受者的预后情况。采用单因素方差分析比较不同肝癌肝移植标准受者年龄、手术时间、无肝期时间和肿瘤最大直径，采用秩和检验比较AFP、终末期肝病模型评分和出血量。采用Kaplan-Meier法绘制生存曲线，采用Log-Rank检验比较生存率。采用卡方检验比较Child分级、肿瘤分化程度等指标。P<0.05为差异有统计学意义。 结果根据肝移植术后病理结果，115例肝癌肝移植受者中符合米兰标准43例；符合美国加州大学旧金山分校(UCSF)标准49例，较米兰标准扩大14.0%；符合杭州标准91例，较米兰标准扩大111.6%，较UCSF标准扩大85.7%。截至2017年12月，115例受者平均随访(19±17)个月，中位生存时间41.5个月(1.0～57.0个月)。除肿瘤最大直径和肿瘤数目外，3组不同肝癌肝移植标准受者均具有可比性(P均>0.05)。不同肝癌肝移植受者术后1～4年总体和和无瘤生存曲线差异均无统计学意义(P均>0.05)。 结论相较于米兰标准和UCSF标准而言，杭州标准安全地扩大了肝癌肝移植适用范围，使更多的原发性肝癌患者受益。     

肝移植治疗原发性肝癌103例疗效观察

目的 比较不同受体选择标准肝癌肝移植的远期疗效,分析肝痛肝移植术后肿瘤复发相关因素.方法 总结北京佑安医院2004年4月至2008年3月间的103例肝癌肝移植的临床资料,按照肿瘤的特征将其分为3组:符合米兰标准组(A组)、超出米兰标准但满足UCSF标准组(B组)和超出UCSF标准组(C组),比较3组的总体生存率及无瘤生存率,并分析影响远期预后的相关因素.结果 103例肝癌肝移植总体1、2、3年存活率分别为84.0%、70.5%和60.2%.其中A组50例,1、2、3年生存率和无瘤生存率分别为93.4%、83.8%、73.2%和97.3%、93.9%、88.7%;B组17例,1、2、3年生存率和无瘤生存率分别为93.3%、79.4%、66.2%和86.7%、79.4%、66.2%;C组36例,1、2、3年生存率和无瘤牛存率分别为67.0%、45.5%、34.1%和65.8%、50.0%、41.7%.远期生存率A组与B组比较无差异(P=0.631),A组、B组与C组比较具有统计学差异(P值分别为0.001,0.045).结论 米兰标准是肝癌肝移植最佳适应证,超出米兰标准但满足UCSF标准也可获得满意的远期疗效;肿瘤的分期和微血管侵犯是影响远期预后的风险因素.     

超“UCSF标准”肝细胞癌肝移植术前经肝动脉化疗栓塞的疗效

目的: 评估经肝动脉化疗栓塞（TACE）在超“UCSF标准”肝细胞癌（HCC）肝移植术前治疗的安全性及疗效。方法: 回顾性分析2003年1月至2013年3月在本院行肝移植治疗的83例超“UCSF标准”的成年HCC病人临床资料,根据术前是否采取TACE治疗分为TACE治疗组（63例）与对照组（20例）。比较两组病人术后急性排异、胆道并发症和血管并发症发生率、无瘤生存率及总生存率。结果: TACE治疗组在肝移植术前平均进行了（2.0±1.3）次TACE疗程,末次治疗至肝移植的平均时间为（15.7±8.4） d。TACE治疗组与对照组相比,在肝移植术后急性排异、肝动脉栓塞和胆道并发症发生率差异无统计学意义（P>0.05）。TACE治疗组无瘤生存率及总生存率明显优于对照组（P<0.05）。分层分析表明,TACE治疗后获得完全反应或部分反应的HCC病人行肝移植1、3、5年无瘤生存率及总生存率明显高于TACE治疗后无反应组（P<0.05）。TACE治疗后肿瘤降期至“UCSF标准”的HCC病人行肝移植1、3、5年无瘤生存率及总生存率明显高于降期治疗后未达到“UCSF标准”的病人（P<0.05）。结论: 肝移植术前TACE治疗可延长病人无瘤生存及总生存时间。肝移植术前TACE降期治疗安全,仅1例发生肝动脉栓塞并发症。     

微小RNA与肝癌肝移植术后肿瘤复发的研究进展

肝细胞癌(肝癌)是全球最常见的恶性肿瘤之一,肝移植是失去根治性切除机会或伴有失代偿性肝硬化肝癌患者唯一有效的治疗方法。然而肝癌肝移植术后肿瘤复发依然严重影响了患者的预后,这也是近年来肝移植领域的研究热点。微小核糖核酸(miRNA)是一类真核细胞中广泛存在长度约21~23 nt的非编码RNA,目前的研究认为miRNA与肝癌肝移植术后肿瘤复发密切相关。联合应用检测miRNA与米兰标准有可能进一步提高肝移植受者的无瘤生存期。miRNA具有调节肿瘤细胞生物学行为的功能,可能成为肝移植术后肿瘤复发的潜在治疗靶点。本文总结了近年来miRNA与肝癌肝移植术后肿瘤复发的相关研究,为肝移植临床医师及科研工作者提供了新的思路。     

肝癌肝移植适应证标准——验证及再思考

目的对不同的原发性肝细胞癌(肝癌)肝移植适应证标准进行评价与验证。方法 2001年至2007年上海七家肝移植中心施行的肝癌肝移植病例共948例,采用Kaplan-Meier法分析符合米兰标准、加利福尼亚标准和上海复旦标准的肝癌肝移植患者的术后4年总体生存率及无复发生存率,并作比较。结果符合米兰标准(369例)、加利福尼亚标准(470例)和上海复旦标准(554例)的患者的术后4年总体生存率及无复发生存率分别为65.8%和74.1%、66.0%和73.6%、63.9%和70.4%。三种标准的总体生存率及无复发生存率比较差异无统计学意义(均为P0.05)。与符合米兰标准的病例相比,超出米兰标准但符合上海复旦标准的185例,其术后4年生存率及无复发生存率分别为61.5%、65.0%,比较差异亦无统计学意义(均为P0.05)。结论上海复旦标准适度扩大了肝癌肝移植适应证范围且生存率满意,可能更符合中国国情。     

以西罗莫司为主的免疫抑制方案在肝细胞癌肝移植术后的应用

目的:评估西罗莫司为主的免疫抑制方案在肝细胞癌行肝移植术后应用的安全性及对术后肿瘤复发和生存的影响。方法:回顾性分析2006年1月至2013年1月在本院肝移植中心因肝细胞癌行肝移植手术的64例病人的临床资料,根据术后是否应用西罗莫司分为西罗莫司组和他克莫司组,比较两组移植术后急性排异、肝动脉栓塞、胆道并发症、切口并发症、代谢疾病、肿瘤复发和病人生存等情况。结果:两组在急性排异、肝动脉栓塞、胆道并发症和切口并发症的发生率方面差异无统计学意义(P>0.05),西罗莫司组新发糖尿病的发生率显著低于他克莫司组,而高血脂的发生率则高于他克莫司组(P<0.05)。与他克莫司组比,西罗莫司组肿瘤1年复发率明显降低,累积生存率明显升高(P<0.05)。结论:肝细胞癌肝移植术后西罗莫司为主的免疫抑制方案并不增加移植术后急性排异、肝动脉栓塞、胆道并发症和切口并发症的发生率,且可延迟肿瘤的复发,提高病人的生存率。     

A single‐center retrospective analysis of liver transplantation on 255 patients with hepatocellular carcinoma

Wang Z‐X, Song S‐H, Teng F, Wang G‐H, Guo W‐Y, Shi X‐M, Ma J, Wu Y‐M, Ding G‐S, Fu Z‐R. A single‐center retrospective analysis of liver transplantation on 255 patients with hepatocellular carcinoma.
Clin Transplant 2010: 24: 752–757. © 2009 John Wiley & Sons A/S. Abstract: Background: Liver transplantation (LT) was advocated as a salvage treatment of choice for patients with unresectable hepatocellular carcinoma (HCC). This study was designed to assess the eligibility of LT criteria for patients with HCC and to analyze the factors influencing the recurrence of HCC following LT, aiming to further improve the efficacy of LT for patients with HCC. Methods: Clinical data of 255 patients with HCC who underwent LT between December 2001 and December 2007 at Shanghai Changzheng Hospital, China were retrospectively analyzed. Results: Among these cases, 75 patients were within the Milan criteria and 180 were beyond it; 110 patients were within the University of California, San Francisco (UCSF) criteria, while 145 were beyond it. The difference in overall survival rates was not only significant between the patients within and beyond the Milan criteria but also between patients within and beyond the UCSF criteria. Tumor‐node‐metastasis (TNM) staging, portal vein tumor thrombus (PVTT), and the pre‐operative alpha‐fetoprotein (AFP) level were independent risk factors affecting the overall survival and post‐operative recurrence‐free survival rates of patients with HCC. Pathological staging and pre‐operative local treatment of HCC had no obvious correlation with the post‐operative recurrence‐free survival rate. Conclusion: LT is an effective treatment modality for HCC. The UCSF criteria did not show better effectiveness than the Milan criteria. TNM staging, PVTT, and the pre‐operative AFP level are closely related to the recurrence of HCC following LT.     

Effects of sirolimus vs. calcineurin inhibitors on renal dysfunction after orthotopic liver transplantation

Small uncontrolled series have suggested that sirolimus favorably impacts renal function after orthotopic liver transplantation (OLT). We sought to retrospectively compare renal dysfunction between cohorts exposed to sirolimus-based and calcineurin inhibitor-based immunosuppression. We retrospectively studied 79 patients converted to sirolimus-based immunosuppression and 100 control subjects continued on calcineurin inhibitor-based immunosuppression after OLT at our institution from 2000 to 2005. We collected clinical, demographic, and medication history. Renal dysfunction was defined as two or more wk of creatinine > or =2.0 mg/dL. Cohorts were compared using Kaplan-Meier survival analysis and Cox proportional hazards modeling. Patients began sirolimus a median 83 d post-OLT and were followed on the medication for median 359 d. Patients in both the sirolimus and calcineurin inhibitor cohorts had median creatinine 1.2 mg/dL at study entry. Sirolimus-based immunosuppression was associated with a 1.8 (0.8-4.3, p = 0.17) hazards ratio for renal dysfunction. Adjusting for presence of hepatocellular carcinoma, combined kidney/liver transplantation, and age, the hazards ratio was 2.0 (0.8-4.8, p = 0.13). These point estimates were not substantially altered after subgroup analysis of sirolimus as the lone immunosuppressant, duration of exposure, and time between OLT and sirolimus conversion. In conclusion, our retrospective, controlled study showed that conversion to sirolimus after OLT did not protect against renal dysfunction. The effect of sirolimus on renal function will need to be prospectively evaluated in a prospective, randomized trial.     

西罗莫司用于治疗肝癌肝移植术后肿瘤复发患者的疗效分析

目的 探讨原发性肝细胞癌(肝癌)肝移植术后肿瘤复发患者在减少钙调磷酸酶抑制剂(他克莫司或环孢素)剂量并联用西罗莫司的临床疗效.方法 24例复发患者随机分为两组:研究组12例,确诊复发后即将钙调磷酸酶抑制剂减量并联合应用西罗莫司(3 mg/d,连用3 d后改为1.5 mg/d,按血药谷浓度4～8 ng/ml调整用量)治疗...     

A Randomized Controlled Trial of Late Conversion from CNI-Based to Sirolimus-Based Immunosuppression Following Renal Transplantation

Maintenance immunosuppression with calcineurin inhibitors (CNIs) following renal transplantation is associated with nephrotoxicity and accelerated graft loss. We aimed to assess whether conversion to sirolimus-based immunosuppression would affect the progression of renal impairment. In this single center, randomized controlled trial, 40 renal transplant recipients between 6 months and 8 years post-transplant were randomly assigned to remain on their CNI (cyclosporin or tacrolimus) or to switch to sirolimus. The primary outcome measure was change in glomerular filtration rate (GFR) measurement at 12 months. Analysis was by intention-to-treat. Of the 40 patients randomized, 2 patients never took the study drugs and were excluded, leaving 19 patients per group. There was a significant change in GFR at 12 months following conversion to sirolimus (12.9 mL/min, 95% CI 6.1-19.7; p < 0.001). Following conversion, the principal adverse events were the development of rashes (68%), particularly acne, and mouth ulcers (32%). No patient in either group experienced an acute rejection episode. In renal transplant recipients, a change in maintenance therapy from CNIs to sirolimus is associated with significant improvement in GFR at 12 months.     

Sirolimus-based immunosuppression for liver transplantation in the presence of extended criteria for hepatocellular carcinoma.

An increasing number of patients with hepatocellular carcinoma (HCC) are undergoing evaluation for listing for liver transplantation. Criteria for selection require ongoing review for suitability. A consecutive series of 40 patients with HCC within the standard Milan criteria (single tumors n = 19 < 5 cm, or up to 3 tumors < 3 cm) and beyond (Extended Criteria; single tumors n = 21 < 7.5 cm, multiple tumors < 5 cm) underwent liver transplant with a sirolimus-based immunosuppressive protocol designed to minimize exposure to calcineurin inhibitors and steroids. At 44.3 +/- 19.3 months (mean +/- standard deviation) follow-up, 1- and 4-year survivals (Kaplan-Meier) are 94.1 +/- 5.7% and 87.4 +/- 9.3%, in the Milan group, respectively, and 90.5 +/- 6.4% and 82.9 +/- 9.3% in the Extended Criteria group, respectively. Five patients died during follow-up, only 1 from recurrent HCC. Five tumor recurrences have occurred at median 17 (mean 22 +/- 17) months posttransplant, 1 in the Milan group and 4 in the Extended Criteria group. Median survival in the patients with recurrent tumor is 42 months (mean 45 +/- 25), and the median postrecurrence survival is 15.5 months (mean 23 +/- 16). The rate of patients who were alive and free of tumor at 1 and 4 years is 94.1 +/- 5.7% and 81.1 +/- 9.9%, respectively, in the Milan group and is 90.5 +/- 6.4% and 76.8 +/- 10.5%, respectively, in the Extended Criteria group. Five patients had sirolimus discontinued for toxicity, while 24 of 35 surviving patients have sirolimus monotherapy immunosuppression. In conclusion, the Milan criteria for liver transplantation in the presence of HCC can be carefully extended without compromising outcomes. This sirolimus based immunosuppression protocol appears to have beneficial effects on tumor recurrence and survival with an acceptable rate of rejection and toxicity.     

Early experience with sirolimus in lung transplant recipients with chronic allograft rejection.

BACKGROUND: Chronic lung allograft rejection, commonly manifest as obliterative bronchiolitis (OB/BOS), hinders long-term survival after lung transplantation (LT). OB/BOS is traditionally treated with augmented immunosuppression and results in short-term stabilization in pulmonary function for most patients. However, peribronchiolar fibroproliferation and airway obstruction usually recur despite initial improvements seen with increases in immunosuppression. In this observational, uncontrolled study, the effect of sirolimus, a novel immunosuppressant with anti-proliferative activity, was assessed in LT patients with OB/BOS. METHODS: Between June 1999 to November 2000, LT recipients with newly diagnosed or progressive OB/BOS received sirolimus in combination with a calcineurin inhibitor (CI) and prednisone. Pulmonary function, laboratory data and adverse effects were monitored for the first 24 weeks of therapy. RESULTS: Sirolimus was utilized in 12 LT recipients with OB/BOS. After drug initiation, 58% of patients required a reduction in CI dose to maintain appropriate CI trough concentrations. Despite CI dose reduction, serum creatinine rose in 75% of patients. Unexpected adverse effects included anemia of chronic disease (100%), edema (50%) and malignancy (17%). For the group, the rate of change in FEV(1) and FEF(25%-75%) was unchanged with sirolimus, but individual responses varied. CONCLUSIONS: For the group, the decline in pulmonary function was not affected by the addition of sirolimus. However, among individuals with rapidly declining pulmonary mechanics, sirolimus resulted in stabilization or improvement in pulmonary function. Significant adverse effects resulted from combination sirolimus plus CI therapy. Until optimal dosing strategies and a more complete adverse effect profile are established, combination therapy should be utilized cautiously in these patients.     

Optimizing the clinical utility of sirolimus‐based immunosuppression for kidney transplantation

While calcineurin inhibitors (CNIs) are effective for preventing acute rejection in kidney transplant recipients, long‐term use may cause chronic kidney injury and is associated with increased risks of cardiovascular events, cancer, and infection‐associated death. Immunosuppression strategies are needed to balance risks of acute and subclinical rejection with long‐term benefits of improved kidney function. Sirolimus, an inhibitor of mammalian target of rapamycin, is used for immunosuppression in kidney transplantation. Its clinical utility has evolved, over more than 15 years, including de novo sirolimus with and without concomitant CNIs and conversion from CNI‐based regimens to sirolimus. Sirolimus‐containing regimens are associated with preservation of good renal function, with promising characteristics for improving long‐term graft and patient survival, including antiviral and anticancer effects. Based on clinical evidence, use of low‐dose sirolimus in a de novo approach with tacrolimus/steroids in the immediate posttransplantation period is appropriate. A feasible alternative is a long term, CNI‐free combination with mycophenolate mofetil (following CNI‐to‐sirolimus conversion at 3‐6 months). These strategies are appropriate for a broad range of patients with various levels of immunologic risk, including those receiving expanded criteria donor kidneys or at increased risk of delayed graft function, particular challenges in Latin America and other global regions.