Heithem Jeddou, Stylianos Tzedakis, Hector Prudhomme, Aline Wautier, Corentin Sumner, Eya Ben Nejma, Mohamad Ali Zorkot, Raffaele Vincenzo De Rosa, Gennaro Mazzarella, Mohamed Ali Chaouch, Michel Samson, Karim Boudjema
Background
Normothermic machine perfusion (NMP) is an alternative to static cold storage (SCS) for liver graft preservation, potentially reducing ischemia–reperfusion injury and improving organ utilization.
Methods
We systematically reviewed RCTs comparing end-ischemic NMP with SCS in adult liver transplantation (MEDLINE, EMBASE, CENTRAL to July 9, 2025). Outcomes of interest included early allograft dysfunction (EAD), organ utilization, patient and graft survival, peak AST, primary non-function (PNF), and biliary complications.
Results
Four RCTs (801 patients; NMP 418; SCS 383) met inclusion. NMP reduced EAD [16.4% vs. 27.2%; RR 0.61, 95% confidence interval (95% CI) 0.38–0.99; p = 0.05] and increased organ utilization (75.5% vs. 69.4%; RR 1.10, 95% CI 1.02–1.18; p = 0.01). No significant differences were observed for patient or graft survival, peak AST, PNF, or biliary complications, though the latter trended in favor of NMP (RR 0.73, p = 0.07).
Conclusion
In adult liver transplantation, NMP reduces EAD and improves organ utilization compared with SCS, without significant differences in survival or major postoperative complications. Evidence remains limited to few trials; larger RCTs are needed to assess long-term benefits.
背景：常温机器灌注（NMP）是静态冷库（SCS）保存肝移植物的替代方法，可能减少缺血再灌注损伤，提高器官利用率。方法：我们系统地回顾了比较终末缺血NMP和SCS在成人肝移植中的rct （MEDLINE， EMBASE， CENTRAL至2025年7月9日）。研究结果包括早期同种异体移植物功能障碍（EAD）、器官利用、患者和移植物存活、AST峰值、原发性无功能（PNF）和胆道并发症。结果：4项rct（801例患者；NMP 418例；SCS 383例）符合纳入标准。NMP减少EAD [16.4% vs. 27.2%；RR 0.61, 95%可信区间（95% CI） 0.38-0.99；p = 0.05]和器官利用率增加（75.5%比69.4%;RR 1.10, 95% CI 1.02-1.18; p = 0.01）。在患者或移植物存活、AST峰值、PNF或胆道并发症方面没有观察到显著差异，尽管后者倾向于NMP （RR 0.73, p = 0.07）。结论：在成人肝移植中，与SCS相比，NMP可减少EAD，提高器官利用率，生存率及术后主要并发症无显著差异。证据仍然局限于少数试验；需要更大的随机对照试验来评估长期效益。
{"title":"Normothermic Perfusion Versus Static Cold Storage in Liver Transplantation: A Meta-Analysis of Randomized Trials","authors":"Heithem Jeddou, Stylianos Tzedakis, Hector Prudhomme, Aline Wautier, Corentin Sumner, Eya Ben Nejma, Mohamad Ali Zorkot, Raffaele Vincenzo De Rosa, Gennaro Mazzarella, Mohamed Ali Chaouch, Michel Samson, Karim Boudjema","doi":"10.1111/ctr.70372","DOIUrl":"10.1111/ctr.70372","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Normothermic machine perfusion (NMP) is an alternative to static cold storage (SCS) for liver graft preservation, potentially reducing ischemia–reperfusion injury and improving organ utilization.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We systematically reviewed RCTs comparing end-ischemic NMP with SCS in adult liver transplantation (MEDLINE, EMBASE, CENTRAL to July 9, 2025). Outcomes of interest included early allograft dysfunction (EAD), organ utilization, patient and graft survival, peak AST, primary non-function (PNF), and biliary complications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Four RCTs (801 patients; NMP 418; SCS 383) met inclusion. NMP reduced EAD [16.4% vs. 27.2%; RR 0.61, 95% confidence interval (95% CI) 0.38–0.99; <i>p</i> = 0.05] and increased organ utilization (75.5% vs. 69.4%; RR 1.10, 95% CI 1.02–1.18; <i>p</i> = 0.01). No significant differences were observed for patient or graft survival, peak AST, PNF, or biliary complications, though the latter trended in favor of NMP (RR 0.73, <i>p</i> = 0.07).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In adult liver transplantation, NMP reduces EAD and improves organ utilization compared with SCS, without significant differences in survival or major postoperative complications. Evidence remains limited to few trials; larger RCTs are needed to assess long-term benefits.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"39 11","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ctr.70372","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145596133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kimberly M. Feeney, Leonie van Leeuwen, Rachel Todd, Avery K. Fortier, Andrew Rosowicz, Antonios Arvelakis, Joseph DiNorcia, Marcelo Facciuto, Matthew Holzner, Jang Moon, Chiara Rocha, Parissa Tabrizian, Thomas Schiano, M. Zeeshan Akhtar, Leona Kim-Schluger, Sander S. Florman
Since FDA approval in 2021, normothermic machine perfusion (NMP) has emerged as a transformative tool to expand transplantation access for patients with end-stage liver disease. This study details the design, implementation, and outcomes of our liver NMP program, highlighting implementation of a stratification algorithm for grafts into low-, medium-, and high-risk categories and evaluation of high-risk grafts from the first 100 cases. A secondary analysis compares NMP outcomes with historical cohorts.
The final analysis included 53 grafts from donation after brain death (DBD) and 39 from donation after circulatory death (DCD) donors, excluding eight NMP grafts that were not transplanted. No significant differences were observed in allograft dysfunction, primary non-function, biliary or arterial complications, or patient survival, even among high-risk graft recipients. NMP significantly reduced intraoperative cryoprecipitate (0.41 vs. 1.44 units, p = 0.003) and platelet (0.59 vs. 1.56 units, p = 0.001) use in DCD recipients. While recipients of DBD-NMP grafts experienced longer ICU stays (17.17 vs. 8.96 days, p = 0.03) and higher rates of renal replacement therapy (41.14% vs. 20.75%, p = 0.04) than the historic cohort, inpatient length of stay and long-term dialysis requirements were unaffected. Higherrisk graft use facilitated transplant access for patients with lower MELD scores at our center.
These findings highlight NMP's potential to safely expand the donor pool, facilitating transplantation of previously non-utilized livers while maintaining comparable outcomes. The risk stratification developed alongside our program provides a practical algorithm to advance equity in organ allocation through NMP by enabling safe access to high-risk grafts and demonstrates its value in optimizing liver transplantation practices.
{"title":"Initial Efforts to Stratify Patients and Donors Utilizing Normothermic Machine Preservation of Livers for Transplant","authors":"Kimberly M. Feeney, Leonie van Leeuwen, Rachel Todd, Avery K. Fortier, Andrew Rosowicz, Antonios Arvelakis, Joseph DiNorcia, Marcelo Facciuto, Matthew Holzner, Jang Moon, Chiara Rocha, Parissa Tabrizian, Thomas Schiano, M. Zeeshan Akhtar, Leona Kim-Schluger, Sander S. Florman","doi":"10.1111/ctr.70378","DOIUrl":"https://doi.org/10.1111/ctr.70378","url":null,"abstract":"<div>\u0000 \u0000 <p>Since FDA approval in 2021, normothermic machine perfusion (NMP) has emerged as a transformative tool to expand transplantation access for patients with end-stage liver disease. This study details the design, implementation, and outcomes of our liver NMP program, highlighting implementation of a stratification algorithm for grafts into low-, medium-, and high-risk categories and evaluation of high-risk grafts from the first 100 cases. A secondary analysis compares NMP outcomes with historical cohorts.</p>\u0000 <p>The final analysis included 53 grafts from donation after brain death (DBD) and 39 from donation after circulatory death (DCD) donors, excluding eight NMP grafts that were not transplanted. No significant differences were observed in allograft dysfunction, primary non-function, biliary or arterial complications, or patient survival, even among high-risk graft recipients. NMP significantly reduced intraoperative cryoprecipitate (0.41 vs. 1.44 units, <i>p</i> = 0.003) and platelet (0.59 vs. 1.56 units, <i>p</i> = 0.001) use in DCD recipients. While recipients of DBD-NMP grafts experienced longer ICU stays (17.17 vs. 8.96 days, <i>p</i> = 0.03) and higher rates of renal replacement therapy (41.14% vs. 20.75%, <i>p</i> = 0.04) than the historic cohort, inpatient length of stay and long-term dialysis requirements were unaffected. Higherrisk graft use facilitated transplant access for patients with lower MELD scores at our center.</p>\u0000 <p>These findings highlight NMP's potential to safely expand the donor pool, facilitating transplantation of previously non-utilized livers while maintaining comparable outcomes. The risk stratification developed alongside our program provides a practical algorithm to advance equity in organ allocation through NMP by enabling safe access to high-risk grafts and demonstrates its value in optimizing liver transplantation practices.</p>\u0000 </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"39 12","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145585273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mustafa Guldan, Rama Al-Shiab, Aladin Rustamov, Lasin Ozbek, Charles J. Ferro, Mehmet Kanbay
Despite substantial advances in surgical technique and immunosuppressive therapy, kidney transplantation continues to face limitations in long-term graft and patient survival. Increasingly, attention is shifting toward the exposome, the comprehensive profile of environmental, social, and biological exposures accumulated across the lifespan, as a critical yet under-investigated determinant of transplant outcomes. Evidence from diverse domains, including air pollution, heavy metal burden, dietary composition, infections, microbiome dynamics, psychosocial context, and digital health engagement, suggests that these factors exert profound effects on immune regulation, metabolic health, and graft integrity. By applying innovative approaches such as exposome-wide association studies, high-resolution biomonitoring, and multi-omics integration, researchers can begin to unravel complex exposure–disease relationships and identify previously unrecognized modifiable risks. Positioning the exposome within the kidney transplantation paradigm offers a pathway toward precision environmental medicine, enabling refined risk stratification, novel preventive strategies, and ultimately improved durability of both graft function and patient survival. However, exposome influences are highly individualized and interact in complex, non-additive ways; current evidence remains largely associative and hypothesis-generating rather than causal.
{"title":"The Exposome Era in Kidney Transplantation: A New Frontier in Graft Outcomes and Precision Medicine","authors":"Mustafa Guldan, Rama Al-Shiab, Aladin Rustamov, Lasin Ozbek, Charles J. Ferro, Mehmet Kanbay","doi":"10.1111/ctr.70384","DOIUrl":"10.1111/ctr.70384","url":null,"abstract":"<div>\u0000 \u0000 <p>Despite substantial advances in surgical technique and immunosuppressive therapy, kidney transplantation continues to face limitations in long-term graft and patient survival. Increasingly, attention is shifting toward the exposome, the comprehensive profile of environmental, social, and biological exposures accumulated across the lifespan, as a critical yet under-investigated determinant of transplant outcomes. Evidence from diverse domains, including air pollution, heavy metal burden, dietary composition, infections, microbiome dynamics, psychosocial context, and digital health engagement, suggests that these factors exert profound effects on immune regulation, metabolic health, and graft integrity. By applying innovative approaches such as exposome-wide association studies, high-resolution biomonitoring, and multi-omics integration, researchers can begin to unravel complex exposure–disease relationships and identify previously unrecognized modifiable risks. Positioning the exposome within the kidney transplantation paradigm offers a pathway toward precision environmental medicine, enabling refined risk stratification, novel preventive strategies, and ultimately improved durability of both graft function and patient survival. However, exposome influences are highly individualized and interact in complex, non-additive ways; current evidence remains largely associative and hypothesis-generating rather than causal.</p>\u0000 </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"39 11","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145586037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The role of failure to rescue (FTR) in solid organ transplantation (SOT) is less clear. This scoping review aimed to evaluate the incidence, complications, and risk factors for FTR in SOT.
Methods
We systematically searched PubMed, Scopus, and Web of Science for studies reporting on FTR in SOT. Data on incidence, complications, risk factors, and definitions were extracted and synthesized narratively due to heterogeneity across studies.
Results
Seven studies were identified: four in liver transplantation, two in lung transplantation, and one in heart transplantation; none addressed kidney or pancreas transplantation. Definitions of FTR varied by time window, complication set, and analytic unit. Reported FTR rates ranged from 4.6% to 39.6% in liver, 19% to 26% in lung, and 11.5% in heart transplantation. Across organs, dialysis-requiring acute kidney injury (AKI) was the most frequent proximate pathway to death. Risk signals spanned patient-level factors (age, comorbidities, frailty/sarcopenia, functional status), donor factors (age, sex, race/ethnicity), and system-level factors (center volume, mortality tertile, insurance coverage). Notably, heart transplantation data revealed higher adjusted odds of FTR among Hispanic recipients.
Conclusions
Evidence on FTR in transplantation remains sparse and heterogeneous, but early findings suggest that both patient vulnerability and system capacity shape rescue outcomes, with AKI consistently emerging as a cross-organ target. Standardized definitions, multicenter analyses, and extension to kidney and pancreas transplantation are needed to establish FTR as a transplant-specific quality metric and to guide interventions that optimize rescue.
背景：抢救失败（FTR）在实体器官移植（SOT）中的作用尚不清楚。本综述旨在评估SOT患者FTR的发生率、并发症和危险因素。方法：我们系统地检索PubMed、Scopus和Web of Science关于SOT中FTR的研究报告。由于研究的异质性，我们提取并综合了关于发病率、并发症、危险因素和定义的数据。结果：确定了7项研究：4项肝移植，2项肺移植，1项心脏移植；没有涉及肾脏或胰腺移植。FTR的定义因时间窗、并发症集和分析单位而异。报道的肝移植的FTR率为4.6% - 39.6%，肺移植为19% - 26%，心脏移植为11.5%。在各个器官中，需要透析的急性肾损伤（AKI）是最常见的直接死亡途径。风险信号跨越患者层面因素（年龄、合并症、虚弱/肌肉减少症、功能状态）、供体因素（年龄、性别、种族/民族）和系统层面因素（中心容积、死亡率、保险覆盖率）。值得注意的是，心脏移植数据显示，西班牙裔受者的FTR调整几率更高。结论：移植中FTR的证据仍然稀少且不一致，但早期研究结果表明，患者易感性和系统能力共同决定了抢救结果，AKI一直是跨器官靶点。需要标准化的定义、多中心分析和扩展到肾脏和胰腺移植，以建立FTR作为移植特异性质量指标，并指导优化抢救的干预措施。
{"title":"Understanding Failure to Rescue in Solid Organ Transplantation: A Scoping Review","authors":"Jiro Kimura, Ayham Asassfeh, Emily Cooper, Kondragunta Rajendra Prasad, Matthew Cooper, Badi Rawashdeh","doi":"10.1111/ctr.70393","DOIUrl":"10.1111/ctr.70393","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The role of failure to rescue (FTR) in solid organ transplantation (SOT) is less clear. This scoping review aimed to evaluate the incidence, complications, and risk factors for FTR in SOT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We systematically searched PubMed, Scopus, and Web of Science for studies reporting on FTR in SOT. Data on incidence, complications, risk factors, and definitions were extracted and synthesized narratively due to heterogeneity across studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Seven studies were identified: four in liver transplantation, two in lung transplantation, and one in heart transplantation; none addressed kidney or pancreas transplantation. Definitions of FTR varied by time window, complication set, and analytic unit. Reported FTR rates ranged from 4.6% to 39.6% in liver, 19% to 26% in lung, and 11.5% in heart transplantation. Across organs, dialysis-requiring acute kidney injury (AKI) was the most frequent proximate pathway to death. Risk signals spanned patient-level factors (age, comorbidities, frailty/sarcopenia, functional status), donor factors (age, sex, race/ethnicity), and system-level factors (center volume, mortality tertile, insurance coverage). Notably, heart transplantation data revealed higher adjusted odds of FTR among Hispanic recipients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Evidence on FTR in transplantation remains sparse and heterogeneous, but early findings suggest that both patient vulnerability and system capacity shape rescue outcomes, with AKI consistently emerging as a cross-organ target. Standardized definitions, multicenter analyses, and extension to kidney and pancreas transplantation are needed to establish FTR as a transplant-specific quality metric and to guide interventions that optimize rescue.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"39 11","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lucia De Gregorio, Oswaldo Aguirre, Gianna Mladenova, Luis Fernandez, Raquel Garcia-Roca
Introduction
Despite the efforts by the Organ Procurement and Transplantation Network (OPTN) to improve utilization of organs from very small pediatric donors, en bloc kidney grafts are still disproportionately discarded. Although associated with increased technical complications, en bloc kidney transplants achieve excellent graft function and longevity. We present our single-center experience with en bloc kidney transplants in adult recipients and compare outcomes between donation after cardio-circulatory death (DCD) and brain death/death by neurologic criteria (BD/DNC) organs.
Methods
Retrospective analysis was completed of all en bloc kidney transplants performed at a single-center academic transplant program, between 2008 and 2023. Two groups were defined according to the type of pediatric donor: DCD or BD/DNC. Demographic data, clinical variables, postoperative complications, and survival outcomes were compared between both groups.
Results
Forty-two adult recipients received pediatric en bloc kidneys, 11 of these from DCD donors. The DGF rate was higher for DCD en bloc kidneys (27% vs. 16% for BD/DNC); however, this difference was not statistically significant. Nearly one third of patients required re-operation during the index transplant admission (28.6%). Four grafts were lost secondary to thrombosis −4(10%). Urological complications occurred in 9.5% of cases. Nevertheless, technical complications were not statistically different between both groups. Patient and graft survival rates were excellent in both groups. All recipients sustained serum creatinine values below 1 mg/dL beyond the first year post-transplant.
Conclusion
Although en bloc kidney transplantation of pediatric en bloc kidneys can be associated with greater rates of technical complications, these grafts can lead to excellent graft function and patient longevity. Diligent patient selection and an experienced surgical team are paramount to optimize the outcomes of en bloc kidney transplants.
尽管器官获取和移植网络（OPTN）努力提高来自非常小的儿童供体的器官的利用率，但整体肾脏移植仍然不成比例地被丢弃。尽管与技术并发症增加有关，整体肾移植获得了良好的移植物功能和寿命。我们介绍了成人肾移植整体移植的单中心经验，并通过神经系统标准（BD/DNC）器官比较了心血管死亡（DCD）和脑死亡/死亡后捐赠的结果。方法：回顾性分析2008年至2023年间在单中心学术移植项目中进行的所有整体肾移植。根据儿童供体类型分为两组：DCD或BD/DNC。比较两组的人口学数据、临床变量、术后并发症和生存结果。结果：42名成人受者接受了儿童整体肾脏，其中11名来自DCD供者。DCD组的DGF率更高（27% vs. BD/DNC组的16%）；然而，这种差异在统计学上并不显著。近三分之一的患者在指数移植入院时需要再次手术（28.6%）。4个移植物因血栓形成而丢失-4（10%）。9.5%的病例出现泌尿系统并发症。然而，技术并发症在两组之间没有统计学差异。两组患者和移植物存活率均极好。移植后一年后，所有受者的血清肌酐值均低于1 mg/dL。结论：尽管儿童整体肾移植可能与更高的技术并发症发生率相关，但这些移植物可以带来良好的移植物功能和患者寿命。勤奋的患者选择和经验丰富的手术团队是优化整体肾移植结果的关键。
{"title":"Utilization of Pediatric En Bloc Kidneys from Donation After Cardio-Circulatory Determination of Death: 15 Years of Experience","authors":"Lucia De Gregorio, Oswaldo Aguirre, Gianna Mladenova, Luis Fernandez, Raquel Garcia-Roca","doi":"10.1111/ctr.70397","DOIUrl":"10.1111/ctr.70397","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Despite the efforts by the Organ Procurement and Transplantation Network (OPTN) to improve utilization of organs from very small pediatric donors, en bloc kidney grafts are still disproportionately discarded. Although associated with increased technical complications, en bloc kidney transplants achieve excellent graft function and longevity. We present our single-center experience with en bloc kidney transplants in adult recipients and compare outcomes between donation after cardio-circulatory death (DCD) and brain death/death by neurologic criteria (BD/DNC) organs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Retrospective analysis was completed of all en bloc kidney transplants performed at a single-center academic transplant program, between 2008 and 2023. Two groups were defined according to the type of pediatric donor: DCD or BD/DNC. Demographic data, clinical variables, postoperative complications, and survival outcomes were compared between both groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Forty-two adult recipients received pediatric en bloc kidneys, 11 of these from DCD donors. The DGF rate was higher for DCD en bloc kidneys (27% vs. 16% for BD/DNC); however, this difference was not statistically significant. Nearly one third of patients required re-operation during the index transplant admission (28.6%). Four grafts were lost secondary to thrombosis −4(10%). Urological complications occurred in 9.5% of cases. Nevertheless, technical complications were not statistically different between both groups. Patient and graft survival rates were excellent in both groups. All recipients sustained serum creatinine values below 1 mg/dL beyond the first year post-transplant.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Although en bloc kidney transplantation of pediatric en bloc kidneys can be associated with greater rates of technical complications, these grafts can lead to excellent graft function and patient longevity. Diligent patient selection and an experienced surgical team are paramount to optimize the outcomes of en bloc kidney transplants.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"39 11","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ctr.70397","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Evelien Kanaan, Sinja Ohlsson, Simone Kathemann, Benas Prusinskas, Sofia Tsaka, Falko M. Heinemann, Andreas Heinold, Maren Schulze, Lars Pape, Elke Lainka
Background
Following pediatric liver transplantation (pLT), the significance and management of donor-specific antibodies (DSA) against human leukocyte antigen (HLA) remain undefined. The aim of this single-center study was to investigate the occurrence of DSA, their clinical impact on predictors for and protectors against DSA.
Patients and Methods
We compared anti-HLA DSA (cutoff for mean fluorescence intensity (MFI) ≥ 1000), clinical and laboratory results and outcome in a routine (RG, n = 142, standard DSA testing) and a hepatopathy group (HG, n = 19, DSA testing following indeterminate hepatopathy) in 161 pLT patients, treated 2000–2021, retrospectively.
Results
40% of RG and 32% of HG patients were DSA+ (39% of all patients, of which 13% with antibody-mediated rejection [AMR]). Most frequent DSA subtypes were HLA-DQ3, -DQ1, -DQ2 in RG and HLA-DQ2, -DR15 in HG. MFI was higher for anti-HLA II DSA (15 257 DSA+ vs. 5500 DSA−, p = 0.003), especially with AMR (21 000 DSA+ with AMR vs. 14 584 DSA+ without AMR, p = 0.042). Predictors for DSA included age at pLT, re-pLT, and cystic fibrosis. Living donation and cold ischemia time <8 h appeared to offer protection. Graft survival was poorer with DSA (RG 78% DSA+ vs. 97% DSA−, p = 0.018, HG 67% DSA+ vs. 100% DSA−, p = 0.0007). Patient survival was 97% for the entire cohort.
Conclusions
DSA were detectable in 39% and associated with AMR in 13% of children post-pLT in addition to worse graft survival in all patients. Patient survival of 97% was not influenced. Potential DSA and predictors and protectors were identified. Therefore, DSA diagnostics are recommended after pLT.
背景：在儿童肝移植（pLT）后，供体特异性抗体（DSA）对抗人类白细胞抗原（HLA）的意义和管理仍不明确。这项单中心研究的目的是调查DSA的发生，它们对DSA预测因子和预防因子的临床影响。患者和方法：我们回顾性比较了2000-2021年治疗的161例pLT患者的常规（RG, n = 142，标准DSA检测）和肝病组（HG, n = 19，不确定肝病后DSA检测）的抗hla DSA（平均荧光强度(MFI)≥1000的截止值）、临床和实验室结果和预后。结果：40%的RG患者和32%的HG患者为DSA+（占所有患者的39%，其中13%为抗体介导的排斥反应[AMR]）。最常见的DSA亚型为RG中的HLA-DQ3、- dq1、- dq2和HG中的HLA-DQ2、- dr15。抗hla - II DSA的MFI较高（15 257个DSA+ vs 5500个DSA-， p = 0.003），尤其是AMR（21 000个AMR + vs 14 584个AMR +， p = 0.042）。DSA的预测因素包括pLT年龄、再pLT年龄和囊性纤维化。结论：39%的plt后儿童检测到DSA， 13%的plt后儿童与AMR相关，所有患者的移植物存活率均较差。97%的患者生存率未受影响。确定了潜在的DSA、预测因子和保护因子。因此，建议在pLT后进行DSA诊断。
{"title":"Assessment of Donor-Specific Human Leukocyte Antigen Antibodies Following Pediatric Liver Transplantation: Predictors, Protectors, and Clinical Relevance","authors":"Evelien Kanaan, Sinja Ohlsson, Simone Kathemann, Benas Prusinskas, Sofia Tsaka, Falko M. Heinemann, Andreas Heinold, Maren Schulze, Lars Pape, Elke Lainka","doi":"10.1111/ctr.70390","DOIUrl":"10.1111/ctr.70390","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Following pediatric liver transplantation (pLT), the significance and management of donor-specific antibodies (DSA) against human leukocyte antigen (HLA) remain undefined. The aim of this single-center study was to investigate the occurrence of DSA, their clinical impact on predictors for and protectors against DSA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Patients and Methods</h3>\u0000 \u0000 <p>We compared anti-HLA DSA (cutoff for mean fluorescence intensity (MFI) ≥ 1000), clinical and laboratory results and outcome in a routine (RG, <i>n</i> = 142, standard DSA testing) and a hepatopathy group (HG, <i>n</i> = 19, DSA testing following indeterminate hepatopathy) in 161 pLT patients, treated 2000–2021, retrospectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>40% of RG and 32% of HG patients were DSA+ (39% of all patients, of which 13% with antibody-mediated rejection [AMR]). Most frequent DSA subtypes were HLA-DQ3, -DQ1, -DQ2 in RG and HLA-DQ2, -DR15 in HG. MFI was higher for anti-HLA II DSA (15 257 DSA+ vs. 5500 DSA−, <i>p </i>= 0.003), especially with AMR (21 000 DSA+ with AMR vs. 14 584 DSA+ without AMR, <i>p </i>= 0.042). Predictors for DSA included age at pLT, re-pLT, and cystic fibrosis. Living donation and cold ischemia time <8 h appeared to offer protection. Graft survival was poorer with DSA (RG 78% DSA+ vs. 97% DSA−, <i>p </i>= 0.018, HG 67% DSA+ vs. 100% DSA−, <i>p </i>= 0.0007). Patient survival was 97% for the entire cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>DSA were detectable in 39% and associated with AMR in 13% of children post-pLT in addition to worse graft survival in all patients. Patient survival of 97% was not influenced. Potential DSA and predictors and protectors were identified. Therefore, DSA diagnostics are recommended after pLT.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"39 11","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ctr.70390","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nan-Su Huang, Jingyao Hong, Akanksha Nalatwad, Yiting Li, Nidhi Ghildayal, Nicole M. Ali, Aarti Mathur, Babak J. Orandi, Dorry L. Segev, Mara A. McAdams-DeMarco
Background
Frail kidney transplant (KT) candidates, characterized by low physical activity/function, have decreased chances of listing and increased risk of waitlist mortality. Impairments in these physical domains contribute to perceived physical burden and may exacerbate one another. Further, understanding the association of each domain individually with adverse outcomes may improve pre-KT risk stratification.
Methods
We leveraged 2708 KT candidates (age ≥ 18) from a two-center prospective cohort study (2014–2024). We assessed physical activity (Minnesota Leisure Time Physical Activity Questionnaire), physical function (gait speed), and physical burden (10 questions from the Kidney Disease Quality of Life Short Form) at evaluation. We quantified the association of these three physical domains with listing (Cox proportional hazards) and waitlist mortality (competing risks, Harrell's C-statistic).
Results
Among 2708 candidates, 40% had low physical activity, 16% had low physical function, and 54% had high physical burden. Candidates with impairment in these three physical domains were less likely to be listed (activity: adjusted hazard ratio [aHR] = 0.86, 95% confidence interval [CI]: 0.75–0.99; function: aHR = 0.54, 95%CI: 0.45–0.64; burden: aHR = 0.75, 95%CI: 0.67–0.83) and had a higher risk of waitlist mortality (activity: adjusted sub-hazard ratio [aSHR] = 1.51, 95%CI: 1.11–2.04; function: aSHR = 1.83, 95%CI: 1.30–2.58; burden: aSHR = 1.40, 95%CI: 1.09–1.82). Physical burden showed the best discrimination in predicting mortality after adjustment (Harrell's C-statistic = 0.6899).
Conclusion
Although impairment in physical activity, function, and burden was all associated with KT listing and waitlist mortality, physical burden was the strongest predictor of waitlist mortality. KT centers should consider measuring physical burden – a simple, low-cost tool to help identify high-risk candidates for prehabilitation.
{"title":"Physical Domains, Access to Kidney Transplantation, and Waitlist Mortality","authors":"Nan-Su Huang, Jingyao Hong, Akanksha Nalatwad, Yiting Li, Nidhi Ghildayal, Nicole M. Ali, Aarti Mathur, Babak J. Orandi, Dorry L. Segev, Mara A. McAdams-DeMarco","doi":"10.1111/ctr.70388","DOIUrl":"10.1111/ctr.70388","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Frail kidney transplant (KT) candidates, characterized by low physical activity/function, have decreased chances of listing and increased risk of waitlist mortality. Impairments in these physical domains contribute to perceived physical burden and may exacerbate one another. Further, understanding the association of each domain individually with adverse outcomes may improve pre-KT risk stratification.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We leveraged 2708 KT candidates (age ≥ 18) from a two-center prospective cohort study (2014–2024). We assessed physical activity (Minnesota Leisure Time Physical Activity Questionnaire), physical function (gait speed), and physical burden (10 questions from the Kidney Disease Quality of Life Short Form) at evaluation. We quantified the association of these three physical domains with listing (Cox proportional hazards) and waitlist mortality (competing risks, Harrell's <i>C</i>-statistic).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 2708 candidates, 40% had low physical activity, 16% had low physical function, and 54% had high physical burden. Candidates with impairment in these three physical domains were less likely to be listed (activity: adjusted hazard ratio [aHR] = 0.86, 95% confidence interval [CI]: 0.75–0.99; function: aHR = 0.54, 95%CI: 0.45–0.64; burden: aHR = 0.75, 95%CI: 0.67–0.83) and had a higher risk of waitlist mortality (activity: adjusted sub-hazard ratio [aSHR] = 1.51, 95%CI: 1.11–2.04; function: aSHR = 1.83, 95%CI: 1.30–2.58; burden: aSHR = 1.40, 95%CI: 1.09–1.82). Physical burden showed the best discrimination in predicting mortality after adjustment (Harrell's <i>C</i>-statistic = 0.6899).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Although impairment in physical activity, function, and burden was all associated with KT listing and waitlist mortality, physical burden was the strongest predictor of waitlist mortality. KT centers should consider measuring physical burden – a simple, low-cost tool to help identify high-risk candidates for prehabilitation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"39 11","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heparin induced thrombocytopenia (HIT) is often suspected among lung transplant recipients (LTRs) due to a high prevalence of thrombocytopenia and frequent heparin use. This study explores the utility of the 4Ts score in stratifying HIT risk among adult LTRs.
Methods
LTRs from a single large transplant center with post-transplant platelet factor 4 (PF4) antibody testing between January 2020 and June 2024 were included in the analysis. The 4Ts score was calculated retrospectively, and the risk of HIT was classified as low (4Ts score ≤3), intermediate (4–5), or high (≥6). The 4Ts risk classification was correlated with HIT laboratory testing results, with a positive serotonin release assay (SRA) representing confirmed HIT.
Results
A total of 205 LTRs were included. The median 4Ts score was 2 (IQR 2–4), 153 patients (74.6%) were classified as low risk, and 52 (25.4%) were intermediate or high risk. Among low-risk patients, none had confirmed HIT. In contrast, among intermediate or high-risk patients, six had HIT (11.5%), representing an overall incidence of 2.9%. Using a low 4Ts score to rule out HIT would have averted 153 PF4 tests (75% of total), 17 SRA tests (50% of total), and nine orders for direct thrombin inhibitors (53% of total).
Conclusion
A low 4Ts score ruled out HIT among LTRs at our large transplant center. Incorporating the 4Ts clinical risk assessment into the diagnostic process may help avoid unnecessary HIT testing and use of alternative anticoagulation.
{"title":"Optimizing Heparin Induced Thrombocytopenia Risk Assessment: Investigating the Role of the 4Ts Score After Lung Transplantation","authors":"Nicole Unwin, Kellie J. Goodlet, Josna Padiyar, Sofya Tokman, Christine Pham, Rhiannon Garcia","doi":"10.1111/ctr.70396","DOIUrl":"10.1111/ctr.70396","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Heparin induced thrombocytopenia (HIT) is often suspected among lung transplant recipients (LTRs) due to a high prevalence of thrombocytopenia and frequent heparin use. This study explores the utility of the 4Ts score in stratifying HIT risk among adult LTRs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>LTRs from a single large transplant center with post-transplant platelet factor 4 (PF4) antibody testing between January 2020 and June 2024 were included in the analysis. The 4Ts score was calculated retrospectively, and the risk of HIT was classified as low (4Ts score ≤3), intermediate (4–5), or high (≥6). The 4Ts risk classification was correlated with HIT laboratory testing results, with a positive serotonin release assay (SRA) representing confirmed HIT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 205 LTRs were included. The median 4Ts score was 2 (IQR 2–4), 153 patients (74.6%) were classified as low risk, and 52 (25.4%) were intermediate or high risk. Among low-risk patients, none had confirmed HIT. In contrast, among intermediate or high-risk patients, six had HIT (11.5%), representing an overall incidence of 2.9%. Using a low 4Ts score to rule out HIT would have averted 153 PF4 tests (75% of total), 17 SRA tests (50% of total), and nine orders for direct thrombin inhibitors (53% of total).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>A low 4Ts score ruled out HIT among LTRs at our large transplant center. Incorporating the 4Ts clinical risk assessment into the diagnostic process may help avoid unnecessary HIT testing and use of alternative anticoagulation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"39 11","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Raphaël M. J. Fischer, Nicolas Muñoz, Olivia Ong, Peter L. Abt, Angelika C. Gruessner, Ronald F. Parsons
Background
Normothermic regional perfusion (NRP) is rapidly gaining adoption for donation after cardiac death (DCD) organ recovery in the United States. However, little is known about trends in NRP procured grafts for simultaneous pancreas–kidney transplantation (SPK).
Design
SPK recipients between January 2021 and June 2025 were identified using the United Network for Organ Sharing (UNOS)/Organ Procurement and Transplantation Network (OPTN) national data.
Patients
DCD-SPK donors and recipients were included and grouped by recovery method.
Measurements
Donor and recipient demographic data were described. Primary outcomes were pancreas and kidney graft survival at 1 year, evaluated with Kaplan–Meier survival curves. Kidney outcomes included delayed graft function and creatinine levels.
Results
A total of 137 DCD SPKs were included, with NRP and super-rapid recovery (SRR) performed in 33 (24%) and 104 (76%) of donors, respectively. Donors in the NRP group were older (28 [22–34] vs. 22 [18–29], p < 0.05) and had a longer withdrawal-to-death time (22 [18–24] vs. 18 [15–22], p < 0.05). Recipients in the NRP group were younger (38 [35–46] vs. 48 [39-55], p < 0.05), more frequently transplanted for Type 1 diabetes, and had worse functional status at the time of transplant. NRP was associated with lower rates of delayed kidney graft function (6% vs. 33%, p < 0.05) and a trend toward lower 6-month creatinine (1.1 vs. 1.3 mg/dL, p = 0.054), with similar 1-year values. One-year pancreas and kidney graft survival following NRP were 91% and 100%, respectively.
Conclusions
Since the introduction of NRP, 24% of the DCD-SPK grafts were procured with NRP. Comparable 1-year kidney and pancreas graft survival between SRR and NRP with lower rates of kidney dysfunction following NRP.
{"title":"Emerging National Trends in Normothermic Regional Perfusion for Simultaneous Pancreas–Kidney Transplantation","authors":"Raphaël M. J. Fischer, Nicolas Muñoz, Olivia Ong, Peter L. Abt, Angelika C. Gruessner, Ronald F. Parsons","doi":"10.1111/ctr.70389","DOIUrl":"10.1111/ctr.70389","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Normothermic regional perfusion (NRP) is rapidly gaining adoption for donation after cardiac death (DCD) organ recovery in the United States. However, little is known about trends in NRP procured grafts for simultaneous pancreas–kidney transplantation (SPK).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Design</h3>\u0000 \u0000 <p>SPK recipients between January 2021 and June 2025 were identified using the United Network for Organ Sharing (UNOS)/Organ Procurement and Transplantation Network (OPTN) national data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Patients</h3>\u0000 \u0000 <p>DCD-SPK donors and recipients were included and grouped by recovery method.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Measurements</h3>\u0000 \u0000 <p>Donor and recipient demographic data were described. Primary outcomes were pancreas and kidney graft survival at 1 year, evaluated with Kaplan–Meier survival curves. Kidney outcomes included delayed graft function and creatinine levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 137 DCD SPKs were included, with NRP and super-rapid recovery (SRR) performed in 33 (24%) and 104 (76%) of donors, respectively. Donors in the NRP group were older (28 [22–34] vs. 22 [18–29], <i>p</i> < 0.05) and had a longer withdrawal-to-death time (22 [18–24] vs. 18 [15–22], <i>p</i> < 0.05). Recipients in the NRP group were younger (38 [35–46] vs. 48 [39-55], <i>p</i> < 0.05), more frequently transplanted for Type 1 diabetes, and had worse functional status at the time of transplant. NRP was associated with lower rates of delayed kidney graft function (6% vs. 33%, <i>p</i> < 0.05) and a trend toward lower 6-month creatinine (1.1 vs. 1.3 mg/dL, <i>p</i> = 0.054), with similar 1-year values. One-year pancreas and kidney graft survival following NRP were 91% and 100%, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Since the introduction of NRP, 24% of the DCD-SPK grafts were procured with NRP. Comparable 1-year kidney and pancreas graft survival between SRR and NRP with lower rates of kidney dysfunction following NRP.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"39 11","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12629267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145548552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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