Pub Date : 2026-01-06DOI: 10.1016/j.trre.2026.101000
Andréa M. Poupard , Georgie Mullin
Primary graft dysfunction (PGD) remains the leading cause of morbidity and mortality following lung transplantation. This narrative review explores current evidence regarding pharmacological strategies for the prevention and management of PGD. A comprehensive literature search identified randomized controlled trials and clinical studies evaluating therapeutic agents targeting ischemia–reperfusion injury and inflammatory pathways. Interventions assessed include inhaled nitric oxide, surfactants, complement inhibitors, platelet-activating factor antagonists, and novel anti-inflammatory agents. Despite promising preclinical data, most trials failed to demonstrate statistically significant improvements in clinical outcomes, primarily due to small sample sizes and methodological heterogeneity. Current PGD management remains supportive and modeled on acute respiratory distress syndrome (ARDS) principles. Future research should focus on multicenter, adequately powered studies testing multimodal strategies combining pharmacologic and procedural interventions. Preventing PGD will be essential to improving early survival and long-term graft function in lung transplant recipients.
{"title":"Therapeutic agents for the prevention of primary graft dysfunction after lung transplantation: A comprehensive narrative review","authors":"Andréa M. Poupard , Georgie Mullin","doi":"10.1016/j.trre.2026.101000","DOIUrl":"10.1016/j.trre.2026.101000","url":null,"abstract":"<div><div>Primary graft dysfunction (PGD) remains the leading cause of morbidity and mortality following lung transplantation. This narrative review explores current evidence regarding pharmacological strategies for the prevention and management of PGD. A comprehensive literature search identified randomized controlled trials and clinical studies evaluating therapeutic agents targeting ischemia–reperfusion injury and inflammatory pathways. Interventions assessed include inhaled nitric oxide, surfactants, complement inhibitors, platelet-activating factor antagonists, and novel anti-inflammatory agents. Despite promising preclinical data, most trials failed to demonstrate statistically significant improvements in clinical outcomes, primarily due to small sample sizes and methodological heterogeneity. Current PGD management remains supportive and modeled on acute respiratory distress syndrome (ARDS) principles. Future research should focus on multicenter, adequately powered studies testing multimodal strategies combining pharmacologic and procedural interventions. Preventing PGD will be essential to improving early survival and long-term graft function in lung transplant recipients.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"40 2","pages":"Article 101000"},"PeriodicalIF":3.6,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145936897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-02DOI: 10.1016/j.trre.2025.100990
Keshvi Chauhan , Neetika Garg , Matthew R. Wolff , Didier A. Mandelbrot , Ravi Dhingra
Most studies concluding that living kidney donation does not increase cardiovascular risk have been conducted in low-risk cohorts. As transplant programs increasingly encounter medically complex donors, careful consideration of long-term cardiovascular risks is essential. There is significant variation among institutions in the practices regarding the selection of living donors. This comprehensive review examines the existing evidence on post-donation cardiovascular outcomes, and prevalent risk factors in the donor candidate population including older age, hypertension, prediabetes, diabetes, obesity, dyslipidemias and metabolic syndrome. The use of atherosclerotic cardiovascular risk calculators for coronary artery disease screening and medical optimization is discussed. Data on outcomes with commonly encountered electrocardiographic and echocardiographic abnormalities identified on screening tests in the donor population are essentially non-existent. To address this gap, we review the literature on their prevalence, natural history and outcomes in the general population. Extrapolating from these data, we make recommendations on risk stratification, decision-making regarding donor selection and follow up. Uncertainties in the context of living kidney donation are highlighted. This review underscores the importance of informed consent, and the need for ongoing research regarding long-term cardiovascular effects of kidney donation in higher-risk individuals.
{"title":"The cardiovascular evaluation of candidates for living kidney donation","authors":"Keshvi Chauhan , Neetika Garg , Matthew R. Wolff , Didier A. Mandelbrot , Ravi Dhingra","doi":"10.1016/j.trre.2025.100990","DOIUrl":"10.1016/j.trre.2025.100990","url":null,"abstract":"<div><div>Most studies concluding that living kidney donation does not increase cardiovascular risk have been conducted in low-risk cohorts. As transplant programs increasingly encounter medically complex donors, careful consideration of long-term cardiovascular risks is essential. There is significant variation among institutions in the practices regarding the selection of living donors. This comprehensive review examines the existing evidence on post-donation cardiovascular outcomes, and prevalent risk factors in the donor candidate population including older age, hypertension, prediabetes, diabetes, obesity, dyslipidemias and metabolic syndrome. The use of atherosclerotic cardiovascular risk calculators for coronary artery disease screening and medical optimization is discussed. Data on outcomes with commonly encountered electrocardiographic and echocardiographic abnormalities identified on screening tests in the donor population are essentially non-existent. To address this gap, we review the literature on their prevalence, natural history and outcomes in the general population. Extrapolating from these data, we make recommendations on risk stratification, decision-making regarding donor selection and follow up. Uncertainties in the context of living kidney donation are highlighted. This review underscores the importance of informed consent, and the need for ongoing research regarding long-term cardiovascular effects of kidney donation in higher-risk individuals.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"40 2","pages":"Article 100990"},"PeriodicalIF":3.6,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145936907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-26DOI: 10.1016/j.trre.2025.100989
Hiroshi Kagawa , Nicolas Contreras , Matthew Goodwin , Laura Frye , Sanjeev Raman , Barbara Cahill , Ramsey Hachem , Matthew Morrell , Craig H. Selzman
Even with the advances of perioperative management and surgical techniques, the outcomes of lung transplantation remain inferior to other solid organ transplantations, in part due to the high occurrence of primary graft dysfunction (PGD) which occurs in up to 30–50 % of lung transplant recipients. Ischemia-reperfusion injury (IRI) is one of the main causes of PGD. Neutrophils play an important role in the mechanism of IRI. Recent studies showed that neutrophil extracellular traps (NETs) also play an important role in development of PGD. There are also some studies about the innovative devices which can remove NETs and pathogenic cytokines. In this review, we discuss the effects of a leukocyte-depleting filter, NETs disruption with Deoxyribonuclease, NETs removal with filter (NucleoCapture), cytokine adsorption filter (CytoSorb), and neutrophil elastase inhibitor for the prevention of PGD. All of these techniques have been studied mainly in animal lung transplant models or ex vivo lung perfusion models, and have shown to have a potential to prevent PGD after clinical lung transplantation. However, clinical trials are needed to critically assess these novel therapies.
{"title":"Targeting leukocytes, neutrophil extracellular traps and cytokines: A conceptual review to prevent primary graft dysfunction after lung transplantation","authors":"Hiroshi Kagawa , Nicolas Contreras , Matthew Goodwin , Laura Frye , Sanjeev Raman , Barbara Cahill , Ramsey Hachem , Matthew Morrell , Craig H. Selzman","doi":"10.1016/j.trre.2025.100989","DOIUrl":"10.1016/j.trre.2025.100989","url":null,"abstract":"<div><div>Even with the advances of perioperative management and surgical techniques, the outcomes of lung transplantation remain inferior to other solid organ transplantations, in part due to the high occurrence of primary graft dysfunction (PGD) which occurs in up to 30–50 % of lung transplant recipients. Ischemia-reperfusion injury (IRI) is one of the main causes of PGD. Neutrophils play an important role in the mechanism of IRI. Recent studies showed that neutrophil extracellular traps (NETs) also play an important role in development of PGD. There are also some studies about the innovative devices which can remove NETs and pathogenic cytokines. In this review, we discuss the effects of a leukocyte-depleting filter, NETs disruption with Deoxyribonuclease, NETs removal with filter (NucleoCapture), cytokine adsorption filter (CytoSorb), and neutrophil elastase inhibitor for the prevention of PGD. All of these techniques have been studied mainly in animal lung transplant models or ex vivo lung perfusion models, and have shown to have a potential to prevent PGD after clinical lung transplantation. However, clinical trials are needed to critically assess these novel therapies.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"40 2","pages":"Article 100989"},"PeriodicalIF":3.6,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145852385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-19DOI: 10.1016/j.trre.2025.100985
Animesh Singla , Shirley Cai , Ahmer Hameed , Henry Pleass , Tess Cooper , Melanie Wyld , Angela C. Webster
Introduction
Balancing bleeding risk with graft thrombosis is a challenge in transplantation surgery. This systematic review assessed the efficacy and safety of intraoperative administration of intravenous (IV) unfractionated heparin (UFH) bolus during adult kidney transplantation.
Methodology
We searched MEDLINE, Embase, and CENTRAL (from inception to May 2025) for comparative studies of any design recruiting adults undergoing living or deceased donor kidney transplantation (PROSPERO CRD42023391473), that examined intraoperative IV UFH as a perioperative intervention. Study quality was assessed using the Newcastle Ottawa Scale. Outcomes: Graft thrombosis (including subgroup analysis of arterial thromboses), bleeding complications, delayed graft function, and transplant nephrectomy. Relative and absolute effects were synthesised using a random-effects model as risk ratio (RR) with 95 % confidence intervals (CI). Certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach.
Results
Three retrospective cohort studies (1989 participants) met inclusion criteria. Study quality was rated as ‘fair’ in two studies and ‘good’ in one study. There was no difference for graft thrombosis with intraoperative IV UFH (3 studies, 1989 participants, RR 1.02, 95 % CI 0.49–2.12, I2 = 0 %, very low certainty evidence). Sub-group analysis also did not identify any difference for arterial thrombosis risk. Nearly all graft thromboses (17/23) resulted in transplant nephrectomy. IV UFH did not increase bleeding complications (3 studies, 1989 participants, RR 1.29, 95 % CI 0.78–2.13, I2 68 %, very low certainty evidence). There was no difference in delayed graft function (2 studies, 461 participants, RR = 0.95, 95 % CI 0.57 to 1.58, I2 = 40 %, very low certainty evidence).
Conclusion
Despite its common use in clinical practice, evidence supporting intraoperative IV UFH during kidney transplant surgery is sparce and of very low certainty. Current evidence does not demonstrate a reduction in graft thrombosis or delayed graft function demonstrated with intraoperative IV UFH, nor a clear increase in bleeding complications. High-quality prospective studies are needed to clarify the net clinical benefit of intraoperative UFH in kidney transplant surgery.
在移植手术中平衡出血风险和移植物血栓形成是一个挑战。本系统综述评估了成人肾移植术中静脉注射未分割肝素（UFH）丸的有效性和安全性。方法：我们检索MEDLINE， Embase和CENTRAL（从成立到2025年5月），以比较任何设计招募接受活体或已故供体肾移植的成人（PROSPERO CRD42023391473）的研究，这些研究检查术中IV UFH作为围手术期干预。研究质量采用纽卡斯尔渥太华量表进行评估。结果：移植物血栓形成（包括动脉血栓亚组分析），出血并发症，移植物功能延迟，移植肾切除术。相对效应和绝对效应采用随机效应模型作为风险比（RR），置信区间为95%。证据的确定性采用GRADE（建议评估、发展和评价分级）方法进行评估。结果：三个回顾性队列研究（1989名参与者）符合纳入标准。研究质量在两项研究中被评为“一般”，在一项研究中被评为“良好”。术中静脉注射UFH在移植物血栓形成方面没有差异（3项研究，1989名参与者，RR 1.02, 95% CI 0.49-2.12, I2 = 0%，非常低确定性证据）。亚组分析也没有发现动脉血栓形成风险的任何差异。几乎所有的移植物血栓形成（17/23）导致移植肾切除术。IV UFH不增加出血并发症（3项研究，1989名受试者，RR 1.29, 95% CI 0.78-2.13, I2 68%，极低确定性证据）。延迟移植物功能没有差异（2项研究，461名参与者，RR = 0.95, 95% CI 0.57至1.58,I2 = 40%，非常低确定性证据）。结论：尽管在临床实践中普遍使用，但支持肾移植手术术中静脉注射UFH的证据很少，而且确定性很低。目前的证据并没有表明术中静脉UFH能减少移植物血栓形成或延迟移植物功能，也没有明显增加出血并发症。需要高质量的前瞻性研究来阐明术中UFH在肾移植手术中的净临床效益。
{"title":"Intraoperative unfractionated heparin (UFH) for kidney transplantation: A systematic review and meta-analysis","authors":"Animesh Singla , Shirley Cai , Ahmer Hameed , Henry Pleass , Tess Cooper , Melanie Wyld , Angela C. Webster","doi":"10.1016/j.trre.2025.100985","DOIUrl":"10.1016/j.trre.2025.100985","url":null,"abstract":"<div><h3>Introduction</h3><div>Balancing bleeding risk with graft thrombosis is a challenge in transplantation surgery. This systematic review assessed the efficacy and safety of intraoperative administration of intravenous (IV) unfractionated heparin (UFH) bolus during adult kidney transplantation.</div></div><div><h3>Methodology</h3><div>We searched MEDLINE, Embase, and CENTRAL (from inception to May 2025) for comparative studies of any design recruiting adults undergoing living or deceased donor kidney transplantation (PROSPERO CRD42023391473), that examined intraoperative IV UFH as a perioperative intervention. Study quality was assessed using the Newcastle Ottawa Scale. Outcomes: Graft thrombosis (including subgroup analysis of arterial thromboses), bleeding complications, delayed graft function, and transplant nephrectomy. Relative and absolute effects were synthesised using a random-effects model as risk ratio (RR) with 95 % confidence intervals (CI). Certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach.</div></div><div><h3>Results</h3><div>Three retrospective cohort studies (1989 participants) met inclusion criteria. Study quality was rated as ‘fair’ in two studies and ‘good’ in one study. There was no difference for graft thrombosis with intraoperative IV UFH (3 studies, 1989 participants, RR 1.02, 95 % CI 0.49–2.12, I<sup>2</sup> = 0 %, very low certainty evidence). Sub-group analysis also did not identify any difference for arterial thrombosis risk. Nearly all graft thromboses (17/23) resulted in transplant nephrectomy. IV UFH did not increase bleeding complications (3 studies, 1989 participants, RR 1.29, 95 % CI 0.78–2.13, I<sup>2</sup> 68 %, very low certainty evidence). There was no difference in delayed graft function (2 studies, 461 participants, RR = 0.95, 95 % CI 0.57 to 1.58, I<sup>2</sup> = 40 %, very low certainty evidence).</div></div><div><h3>Conclusion</h3><div>Despite its common use in clinical practice, evidence supporting intraoperative IV UFH during kidney transplant surgery is sparce and of very low certainty. Current evidence does not demonstrate a reduction in graft thrombosis or delayed graft function demonstrated with intraoperative IV UFH, nor a clear increase in bleeding complications. High-quality prospective studies are needed to clarify the net clinical benefit of intraoperative UFH in kidney transplant surgery.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"40 1","pages":"Article 100985"},"PeriodicalIF":3.6,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145806976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-17DOI: 10.1016/j.trre.2025.100988
Maggie Cheng , Steven Cao Tri Huynh , Reid Dale , Maria Elizabeth Currie
Current multi-organ candidates are prioritized primarily based on single-organ risk scores. Once the primary organ is allocated, the secondary organ follows to the same recipient, resulting in waitlisted single-organ candidates being skipped in allocation.
Our previous work examined the ethical and statistical alignment of single-organ risk scores. Here, we aim to extend our analysis to multi-organ transplantation policies in the United States, surveying the current state of multi-organ candidate prioritization and the challenges of conducting high-quality research in multi-organ transplantation.
We systematically searched PubMed for published literature on the allocation of all multi-organ pairs involving the liver, kidney, lungs, and heart. After screening based on our inclusion and exclusion criteria, we identified 126 articles to include in this review. These include 31 articles for Heart-Lung, 24 for Heart-Kidney, 52 for Liver-Kidney, and 19 for Liver-Heart transplantation. We did not discuss the remaining organ pairs due to insufficient literature to provide a balanced analysis.
Provider-, center-, and region-dependent variations exist in multi-organ practices due to evolving national guidelines and a lack of standardized institutional protocols for candidate evaluation and listing. The use of single-organ risk scores in multi-organ allocation has not been statistically validated, therefore raising concerns about applicability.
Multi-organ transplant research relies heavily on single-center reports, case studies, and registry-based analyses. The frequent re-use of national registry data limits the novelty and reliability of multi-organ research. We encourage future efforts to consider exploratory, prospective, and perhaps randomized-controlled trials to advance understanding and strengthen the evidence base in multi-organ transplantation.
{"title":"History and challenges of multi-organ allocation in the United States: A systematic review","authors":"Maggie Cheng , Steven Cao Tri Huynh , Reid Dale , Maria Elizabeth Currie","doi":"10.1016/j.trre.2025.100988","DOIUrl":"10.1016/j.trre.2025.100988","url":null,"abstract":"<div><div>Current multi-organ candidates are prioritized primarily based on single-organ risk scores. Once the primary organ is allocated, the secondary organ follows to the same recipient, resulting in waitlisted single-organ candidates being skipped in allocation.</div><div>Our previous work examined the ethical and statistical alignment of single-organ risk scores. Here, we aim to extend our analysis to multi-organ transplantation policies in the United States, surveying the current state of multi-organ candidate prioritization and the challenges of conducting high-quality research in multi-organ transplantation.</div><div>We systematically searched PubMed for published literature on the allocation of all multi-organ pairs involving the liver, kidney, lungs, and heart. After screening based on our inclusion and exclusion criteria, we identified 126 articles to include in this review. These include 31 articles for Heart-Lung, 24 for Heart-Kidney, 52 for Liver-Kidney, and 19 for Liver-Heart transplantation. We did not discuss the remaining organ pairs due to insufficient literature to provide a balanced analysis.</div><div>Provider-, center-, and region-dependent variations exist in multi-organ practices due to evolving national guidelines and a lack of standardized institutional protocols for candidate evaluation and listing. The use of single-organ risk scores in multi-organ allocation has not been statistically validated, therefore raising concerns about applicability.</div><div>Multi-organ transplant research relies heavily on single-center reports, case studies, and registry-based analyses. The frequent re-use of national registry data limits the novelty and reliability of multi-organ research. We encourage future efforts to consider exploratory, prospective, and perhaps randomized-controlled trials to advance understanding and strengthen the evidence base in multi-organ transplantation.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"40 1","pages":"Article 100988"},"PeriodicalIF":3.6,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145822564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-16DOI: 10.1016/j.trre.2025.100987
Nikolaos Koliakos , Phong A. Tran , Dimitrios Papakonstantinou , Nikolaos Machairas , Hung N. Dang , Georgios C. Sotiropoulos , Dimitrios Schizas , Valerio Lucidi
Organ transplantation remains the gold-standard treatment for end-stage organ failure, with brain-dead donors being the primary source of transplantable organs. The timing of organ procurement—particularly the interval between brain death declaration and cold perfusion—has emerged as a critical factor influencing graft outcomes. This systematic review synthesizes evidence on the impact of procurement timing on liver, pancreas, and kidney transplantation outcomes. A comprehensive literature search identified six studies (196,389 patients) meeting inclusion criteria. For patients undergoing liver transplantation, longer procurement intervals (median 34.6 vs. 10.5 h) were associated with improved graft survival and reduced acute rejection. In patients undergoing pancreas transplantation, each 10-h delay correlated with a 5.6 % reduction in graft loss and a 6.3 % lower rejection risk. Studies looking into outcomes after kidney transplantation demonstrated that extended intervals (>20 h) reduced delayed graft function (DGF) in younger donors and improved long-term graft survival, without increasing rejection rates. Contrary to traditional beliefs, prolonged procurement intervals did not harm abdominal organ viability and, in some cases, enhanced outcomes, likely due to improved donor stabilization and reduced inflammatory injury. These findings suggest that transplant teams can adopt more flexible procurement timelines while maintaining graft quality. However, study heterogeneity and limited data warrant further research to refine optimal timing strategies. This review supports a paradigm shift toward individualized, organ-specific procurement protocols to maximize transplantation success.
{"title":"Optimizing the timing of organ procurement from donors after brainstem death: Impact on outcomes in abdominal organ transplantation – A systematic review","authors":"Nikolaos Koliakos , Phong A. Tran , Dimitrios Papakonstantinou , Nikolaos Machairas , Hung N. Dang , Georgios C. Sotiropoulos , Dimitrios Schizas , Valerio Lucidi","doi":"10.1016/j.trre.2025.100987","DOIUrl":"10.1016/j.trre.2025.100987","url":null,"abstract":"<div><div>Organ transplantation remains the gold-standard treatment for end-stage organ failure, with brain-dead donors being the primary source of transplantable organs. The timing of organ procurement—particularly the interval between brain death declaration and cold perfusion—has emerged as a critical factor influencing graft outcomes. This systematic review synthesizes evidence on the impact of procurement timing on liver, pancreas, and kidney transplantation outcomes. A comprehensive literature search identified six studies (196,389 patients) meeting inclusion criteria. For patients undergoing liver transplantation, longer procurement intervals (median 34.6 vs. 10.5 h) were associated with improved graft survival and reduced acute rejection. In patients undergoing pancreas transplantation, each 10-h delay correlated with a 5.6 % reduction in graft loss and a 6.3 % lower rejection risk. Studies looking into outcomes after kidney transplantation demonstrated that extended intervals (>20 h) reduced delayed graft function (DGF) in younger donors and improved long-term graft survival, without increasing rejection rates. Contrary to traditional beliefs, prolonged procurement intervals did not harm abdominal organ viability and, in some cases, enhanced outcomes, likely due to improved donor stabilization and reduced inflammatory injury. These findings suggest that transplant teams can adopt more flexible procurement timelines while maintaining graft quality. However, study heterogeneity and limited data warrant further research to refine optimal timing strategies. This review supports a paradigm shift toward individualized, organ-specific procurement protocols to maximize transplantation success.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"40 1","pages":"Article 100987"},"PeriodicalIF":3.6,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145789599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-15DOI: 10.1016/j.trre.2025.100986
Zhi-Cheng Gao , Hui Wan , Guan-Yue Shan , Yu-Xin Zhang , Zi-Jun Sun , Yun-Peng Shi , Hai-Jun Li
Natural killer (NK) cells are crucial components of the innate immune system and are abundantly present in the liver, a unique immune organ frequently subjected to clinical transplantation. NK cells regulate their functional state through a finely tuned balance between activating and inhibitory receptors, allowing them to eliminate target cells independently of major histocompatibility complex class I (MHC-I) restriction. In the context of liver transplantation, NK cells respond dynamically to ischemia-reperfusion injury, donor-recipient immune mismatch and immunosuppressive treatments, thereby influencing graft acceptance, rejection and infection control. Activated NK cells release a broad range of cytokines and chemokines, shaping both innate and adaptive immune responses. This review highlights the multifaceted roles of NK cells in transplant immunity, emphasizes their clinical and translational significance, and summarizes emerging therapeutic strategies that target NK cells. Collectively, it provides insights into NK cell biology and underscores their potential in improving long-term outcomes after liver transplantation.
{"title":"The role of natural killer cells in the immune response after liver transplantation","authors":"Zhi-Cheng Gao , Hui Wan , Guan-Yue Shan , Yu-Xin Zhang , Zi-Jun Sun , Yun-Peng Shi , Hai-Jun Li","doi":"10.1016/j.trre.2025.100986","DOIUrl":"10.1016/j.trre.2025.100986","url":null,"abstract":"<div><div>Natural killer (NK) cells are crucial components of the innate immune system and are abundantly present in the liver, a unique immune organ frequently subjected to clinical transplantation. NK cells regulate their functional state through a finely tuned balance between activating and inhibitory receptors, allowing them to eliminate target cells independently of major histocompatibility complex class I (MHC-I) restriction. In the context of liver transplantation, NK cells respond dynamically to ischemia-reperfusion injury, donor-recipient immune mismatch and immunosuppressive treatments, thereby influencing graft acceptance, rejection and infection control. Activated NK cells release a broad range of cytokines and chemokines, shaping both innate and adaptive immune responses. This review highlights the multifaceted roles of NK cells in transplant immunity, emphasizes their clinical and translational significance, and summarizes emerging therapeutic strategies that target NK cells. Collectively, it provides insights into NK cell biology and underscores their potential in improving long-term outcomes after liver transplantation.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"40 1","pages":"Article 100986"},"PeriodicalIF":3.6,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145776946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-12DOI: 10.1016/j.trre.2025.100984
Wellgner Fernandes Oliveira Amador , Isabelle Castro Vitor , Milena Ramos Tomé , Igor Boechat Silveira , Marina de Assis Bezerra Cavalcanti Leite , Pedro Robson Costa Passos , Valbert Oliveira Costa Filho , Mariana Macambira Noronha , Yohanna Idsabella Rossi , Rodrigo Vieira Motta , Guilherme Grossi Lopes Cançado
Autoimmune hepatitis (AIH) recurrence after liver transplantation (LT) compromises graft function and outcomes. Evidence on risk factors is heterogeneous. We assessed recurrence rates and patient-, immunological-, clinical-, and donor-related predictors. A systematic review and meta-analysis of observational studies of LT recipients with AIH was conducted. PubMed, Embase, and CENTRAL were searched. Outcomes were recurrence incidence and associated risk factors. Random-effects models were fitted in R, with pooled proportions, odds ratios (ORs), and mean differences (MDs). Thirty-nine studies (n = 2600) met inclusion criteria. The pooled recurrence proportion was 21 % (95 %CI, 18 to 25 %). Recurrence was more frequent in children than adults (31 % vs 21 %; p-interaction = 0.03). Younger age was associated with recurrence (MD, −6.60 years; 95 %CI, −11.43 to −1.76). Acute rejection (OR, 1.92; 95 %CI, 1.11 to 3.31) and chronic rejection (OR, 2.64; 95 %CI, 0.99 to 6.99) were significant predictors. No significant associations were observed for sex, MELD score, AIH subtype, HLA-DR3/DR4 status, primary calcineurin inhibitor (tacrolimus vs cyclosporine), or donor type. Overall, one in five LT recipients with AIH experience recurrence, with a higher burden in pediatric and younger patients. Younger age and prior acute or chronic rejection confer the greatest risk. Targeted monitoring and tailored immunosuppression may help mitigate recurrence.
{"title":"Global epidemiology and determinants of autoimmune hepatitis recurrence post- liver transplantation: A systematic review and meta-analysis","authors":"Wellgner Fernandes Oliveira Amador , Isabelle Castro Vitor , Milena Ramos Tomé , Igor Boechat Silveira , Marina de Assis Bezerra Cavalcanti Leite , Pedro Robson Costa Passos , Valbert Oliveira Costa Filho , Mariana Macambira Noronha , Yohanna Idsabella Rossi , Rodrigo Vieira Motta , Guilherme Grossi Lopes Cançado","doi":"10.1016/j.trre.2025.100984","DOIUrl":"10.1016/j.trre.2025.100984","url":null,"abstract":"<div><div>Autoimmune hepatitis (AIH) recurrence after liver transplantation (LT) compromises graft function and outcomes. Evidence on risk factors is heterogeneous. We assessed recurrence rates and patient-, immunological-, clinical-, and donor-related predictors. A systematic review and meta-analysis of observational studies of LT recipients with AIH was conducted. PubMed, Embase, and CENTRAL were searched. Outcomes were recurrence incidence and associated risk factors. Random-effects models were fitted in R, with pooled proportions, odds ratios (ORs), and mean differences (MDs). Thirty-nine studies (<em>n</em> = 2600) met inclusion criteria. The pooled recurrence proportion was 21 % (95 %CI, 18 to 25 %). Recurrence was more frequent in children than adults (31 % vs 21 %; p-interaction = 0.03). Younger age was associated with recurrence (MD, −6.60 years; 95 %CI, −11.43 to −1.76). Acute rejection (OR, 1.92; 95 %CI, 1.11 to 3.31) and chronic rejection (OR, 2.64; 95 %CI, 0.99 to 6.99) were significant predictors. No significant associations were observed for sex, MELD score, AIH subtype, HLA-DR3/DR4 status, primary calcineurin inhibitor (tacrolimus vs cyclosporine), or donor type. Overall, one in five LT recipients with AIH experience recurrence, with a higher burden in pediatric and younger patients. Younger age and prior acute or chronic rejection confer the greatest risk. Targeted monitoring and tailored immunosuppression may help mitigate recurrence.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"40 1","pages":"Article 100984"},"PeriodicalIF":3.6,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ischemia-reperfusion injury (IRI) critically affects graft survival following organ transplantation, where complement activation mediates the inflammation, endothelial damage, and adaptive immune responses. This review synthesizes the mechanisms through which the classical, lectin, and alternative complement pathways drive organ-specific IRI pathophysiology by generating anaphylatoxins (C3a/C5a) and membrane attack complexes (C5b-9). Specifically, locally synthesized C3 predominates in renal tubular injury, hepatic C3a/C5a paradoxically promote regeneration while exacerbating inflammation, cardiac C4d/C3d deposits correlate with rejection, and lectin pathway activation (notably via mannose-binding lectin, MBL) underlies primary graft dysfunction (PGD) in lung transplantation. Advances in therapeutic research highlight the values of complement inhibitors, including anti-C5 agents (e.g., eculizumab) that mitigate delayed graft function (DGF) in kidney transplantation, C1 esterase inhibitors that attenuate IRI and antibody-mediated rejection (AMR), C5a receptor antagonists (e.g., PMX53) that extend graft survival in preclinical models, and soluble complement receptor 1 (sCR1) that alleviates multi-organ IRI. Future research should focus on optimizing organ-specific targeting strategies, validating the long-term efficacy and safety of these agents via clinical trials, and exploring synergistic immunomodulatory approaches to further improve transplantation outcomes.
{"title":"Research progress on the complement system in ischemia-reperfusion injury of organ transplantation","authors":"Cheng Zhang , Kun Dong , Junze Chen , Guanmiao Chen , Chunqiang Dong","doi":"10.1016/j.trre.2025.100981","DOIUrl":"10.1016/j.trre.2025.100981","url":null,"abstract":"<div><div>Ischemia-reperfusion injury (IRI) critically affects graft survival following organ transplantation, where complement activation mediates the inflammation, endothelial damage, and adaptive immune responses. This review synthesizes the mechanisms through which the classical, lectin, and alternative complement pathways drive organ-specific IRI pathophysiology by generating anaphylatoxins (C3a/C5a) and membrane attack complexes (C5b-9). Specifically, locally synthesized C3 predominates in renal tubular injury, hepatic C3a/C5a paradoxically promote regeneration while exacerbating inflammation, cardiac C4d/C3d deposits correlate with rejection, and lectin pathway activation (notably via mannose-binding lectin, MBL) underlies primary graft dysfunction (PGD) in lung transplantation. Advances in therapeutic research highlight the values of complement inhibitors, including anti-C5 agents (e.g., eculizumab) that mitigate delayed graft function (DGF) in kidney transplantation, C1 esterase inhibitors that attenuate IRI and antibody-mediated rejection (AMR), C5a receptor antagonists (e.g., PMX53) that extend graft survival in preclinical models, and soluble complement receptor 1 (sCR1) that alleviates multi-organ IRI. Future research should focus on optimizing organ-specific targeting strategies, validating the long-term efficacy and safety of these agents via clinical trials, and exploring synergistic immunomodulatory approaches to further improve transplantation outcomes.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"40 1","pages":"Article 100981"},"PeriodicalIF":3.6,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-07DOI: 10.1016/j.trre.2025.100983
Emmanouil Giorgakis , Paulo N. Martins , Amelia J. Hessheimer , Davide Ghinolfi , Dimitrios Moris , Anastasios Giannou , Esteban Calderon , Amit Mathur , Nigel Heaton , Andrea Schlegel
Liver transplant (LT) waitlists keep growing globally. Simultaneously, donation after circulatory death (DCD) LT has evolved from a marginal to a mainstream practice, now representing a vital strategy to expand the donor pool. Historically, livers from older DCD donors (≥60 years) were regarded as high risk due to concerns about post-transplant cholangiopathy, primary non-function, and poorer long-term survival. These risks led many centers to exclude grafts from older DCD donors. Nonetheless, the adoption of dynamic preservation technologies, including in situ normothermic regional perfusion, ex situ normothermic machine perfusion, and ex situ hypothermic oxygenated perfusion modalities, has fundamentally altered this risk-benefit calculus. Contemporary data from national and multicenter registries demonstrate that older DCD grafts can reach patient and graft survival rates comparable to those of younger DCD and donation after brain death livers when dynamically recovered and/or preserved. The United Kingdom and Spain have led this growth, routinely transplanting donors in their 60s and 70s. Italy has pushed boundaries further with the successful use of nonagenarian donors under sequential perfusion protocols. The United States, historically hesitant with older DCDs, has rapidly adopted them since 2020, driven by the approval of machine perfusion and changes in organ allocation. These worldwide trends underscore a fundamental shift: advanced age alone is no longer a definitive barrier to DCD LT when combined with advanced preservation, graft assessment, and careful recipient selection.
{"title":"The expanding frontier: Global use of DCD livers from donors over 60 years","authors":"Emmanouil Giorgakis , Paulo N. Martins , Amelia J. Hessheimer , Davide Ghinolfi , Dimitrios Moris , Anastasios Giannou , Esteban Calderon , Amit Mathur , Nigel Heaton , Andrea Schlegel","doi":"10.1016/j.trre.2025.100983","DOIUrl":"10.1016/j.trre.2025.100983","url":null,"abstract":"<div><div>Liver transplant (LT) waitlists keep growing globally. Simultaneously, donation after circulatory death (DCD) LT has evolved from a marginal to a mainstream practice, now representing a vital strategy to expand the donor pool. Historically, livers from older DCD donors (≥60 years) were regarded as high risk due to concerns about post-transplant cholangiopathy, primary non-function, and poorer long-term survival. These risks led many centers to exclude grafts from older DCD donors. Nonetheless, the adoption of dynamic preservation technologies, including in situ normothermic regional perfusion, ex situ normothermic machine perfusion, and ex situ hypothermic oxygenated perfusion modalities, has fundamentally altered this risk-benefit calculus. Contemporary data from national and multicenter registries demonstrate that older DCD grafts can reach patient and graft survival rates comparable to those of younger DCD and donation after brain death livers when dynamically recovered and/or preserved. The United Kingdom and Spain have led this growth, routinely transplanting donors in their 60s and 70s. Italy has pushed boundaries further with the successful use of nonagenarian donors under sequential perfusion protocols. The United States, historically hesitant with older DCDs, has rapidly adopted them since 2020, driven by the approval of machine perfusion and changes in organ allocation. These worldwide trends underscore a fundamental shift: advanced age alone is no longer a definitive barrier to DCD LT when combined with advanced preservation, graft assessment, and careful recipient selection.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"40 1","pages":"Article 100983"},"PeriodicalIF":3.6,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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