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}
Pub Date : 2025-12-04DOI: 10.1016/j.trre.2025.100982
Pedro Fragoso , Andreia Borges , Francisco Caramelo , Helena Oliveira Sá , Arnaldo Figueiredo , Rui Alves , Rita Leal
Background
Kidney transplant recipients with graft failure face reduced access to retransplantation due to sensitization. Evidence-based guidance on optimal immunosuppression (IS) management after graft loss is limited. This systematic review with meta-analysis assessed the impact of rapid versus prolonged IS withdrawal on sensitization and safety outcomes.
Methods
Cohort studies comparing IS withdrawal strategies after graft failure were systematically reviewed. Outcomes included HLA sensitization, graft nephrectomy, hospitalization, and mortality. Searches were conducted in Medline, Embase, and the Cochrane Library. Pooled odds ratios (ORs) and weighted mean differences (WMD) were calculated using a random-effects model.
Results
Thirteen studies comprising 1531 patients were included. Prolonging immunosuppression (>3 months of at least two immunosuppressants) was associated with significantly lower odds of graft exclusion (OR 0.41; 95 % CI 0.27–0.64), and a trend toward reduced donor-specific antibody formation and cPRA stabilization, although not statistically significant. Sensitivity analysis confirmed an association between early IS withdrawal and higher cPRA at follow-up (WMD +0.30, 0.01–0.59). The IS withdrawal strategy did not impact hospitalization, mortality, or retransplantation.
Conclusion
Prolonging IS after kidney graft failure reduces nephrectomy risk and favours a decrease in HLA sensitization, without added morbidity and mortality. Further prospective studies are warranted to provide stronger evidence-based data.
背景：肾移植失败的受者由于致敏性降低了再移植的机会。基于证据的移植物丢失后最佳免疫抑制（IS）管理指导是有限的。本系统综述和荟萃分析评估了快速和长期停药对致敏性和安全性结果的影响。方法：系统回顾比较移植失败后IS退出策略的队列研究。结果包括HLA致敏、移植肾切除术、住院和死亡率。在Medline、Embase和Cochrane图书馆进行了检索。采用随机效应模型计算合并优势比（ORs）和加权平均差（WMD）。结果：纳入13项研究，1531例患者。延长免疫抑制（至少使用两种免疫抑制剂3个月）与移植物排斥几率显著降低相关（OR 0.41; 95% CI 0.27-0.64），并有减少供体特异性抗体形成和cPRA稳定的趋势，尽管没有统计学意义。敏感性分析证实早期IS戒断与随访时较高的cPRA之间存在关联（WMD +0.30, 0.01-0.59）。IS退出策略不影响住院、死亡率或再移植。结论：肾移植失败后延长IS可降低肾切除术风险，有利于降低HLA敏化，未增加发病率和死亡率。进一步的前瞻性研究有必要提供更有力的循证数据。
{"title":"The impact of immunosuppression withdrawal strategies on sensitization and safety outcomes after kidney transplant failure: A systematic review with meta-analysis","authors":"Pedro Fragoso , Andreia Borges , Francisco Caramelo , Helena Oliveira Sá , Arnaldo Figueiredo , Rui Alves , Rita Leal","doi":"10.1016/j.trre.2025.100982","DOIUrl":"10.1016/j.trre.2025.100982","url":null,"abstract":"<div><h3>Background</h3><div>Kidney transplant recipients with graft failure face reduced access to retransplantation due to sensitization. Evidence-based guidance on optimal immunosuppression (IS) management after graft loss is limited. This systematic review with meta-analysis assessed the impact of rapid versus prolonged IS withdrawal on sensitization and safety outcomes.</div></div><div><h3>Methods</h3><div>Cohort studies comparing IS withdrawal strategies after graft failure were systematically reviewed. Outcomes included HLA sensitization, graft nephrectomy, hospitalization, and mortality. Searches were conducted in Medline, Embase, and the Cochrane Library. Pooled odds ratios (ORs) and weighted mean differences (WMD) were calculated using a random-effects model.</div></div><div><h3>Results</h3><div>Thirteen studies comprising 1531 patients were included. Prolonging immunosuppression (>3 months of at least two immunosuppressants) was associated with significantly lower odds of graft exclusion (OR 0.41; 95 % CI 0.27–0.64), and a trend toward reduced donor-specific antibody formation and cPRA stabilization, although not statistically significant. Sensitivity analysis confirmed an association between early IS withdrawal and higher cPRA at follow-up (WMD +0.30, 0.01–0.59). The IS withdrawal strategy did not impact hospitalization, mortality, or retransplantation.</div></div><div><h3>Conclusion</h3><div>Prolonging IS after kidney graft failure reduces nephrectomy risk and favours a decrease in HLA sensitization, without added morbidity and mortality. Further prospective studies are warranted to provide stronger evidence-based data.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"40 1","pages":"Article 100982"},"PeriodicalIF":3.6,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717243","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 : 2025-12-03DOI: 10.1016/j.trre.2025.100980
Annie Mae Goncalves Bullock , Ascanio Tridente , Nina C. Dempsey
Systemic hyper-inflammation is an established cause of organ dysfunction, evidenced by the multi-organ failure observed in sepsis. Similarly, the process of death invokes a complex set of events leading to profound hyper-inflammation. It is reasonable to infer that in deceased organ donors, death-induced hyperinflammation could have significant consequences for organs being offered for transplant. This systematic review aimed to; 1) clarify what is currently known about the sources of inflammation following death, and 2) systematically review the current body of evidence reporting levels of inflammation in deceased donors and living donors and linking donor inflammation with kidney transplant outcome. The systematic review was conducted in agreement with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines 8. We searched the Medline, Web of Science, Scopus and CINHAL databases from January 2000 to March 2023 for articles relating donor inflammation with kidney transplant outcomes. The National Institute of Health ‘Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies’ was used to assess validity of studies. Twenty-one studies were analysed, collectively totalling 3397 donors and 4596 recipients. A high degree of heterogeneity in inflammatory markers and transplant outcomes studied existed between studies, yet collective evidence showed higher inflammation, complement activation, and tissue injury in deceased donors compared with living donors, and strongly suggested associations with poorer short- and long-term transplant outcomes.
全身过度炎症是器官功能障碍的一个确定的原因，在败血症中观察到的多器官衰竭证明了这一点。同样，死亡的过程会引发一系列复杂的事件，导致严重的高度炎症。我们有理由推断，在已故的器官供者中，死亡引起的过度炎症可能对供移植的器官产生重大影响。本系统综述旨在；1)澄清目前已知的死亡后炎症的来源，2)系统地回顾目前报告死亡供体和活体供体炎症水平的证据，并将供体炎症与肾移植结果联系起来。系统评价按照系统评价和荟萃分析的首选报告项目（PRISMA）指南进行8。从2000年1月到2023年3月，我们检索了Medline、Web of Science、Scopus和CINHAL数据库，查找供体炎症与肾移植结果相关的文章。使用美国国立卫生研究院的“观察性队列和横断面研究质量评估工具”来评估研究的有效性。分析了21项研究，总共有3397名捐赠者和4596名接受者。研究之间存在炎症标志物和移植结果的高度异质性，但集体证据表明，与活体供体相比，死亡供体的炎症、补体激活和组织损伤更高，并强烈提示与较差的短期和长期移植结果相关。
{"title":"Inflammation in deceased kidney donors in the pre-organ retrieval period and the association with transplant outcomes: A systematic review","authors":"Annie Mae Goncalves Bullock , Ascanio Tridente , Nina C. Dempsey","doi":"10.1016/j.trre.2025.100980","DOIUrl":"10.1016/j.trre.2025.100980","url":null,"abstract":"<div><div>Systemic hyper-inflammation is an established cause of organ dysfunction, evidenced by the multi-organ failure observed in sepsis. Similarly, the process of death invokes a complex set of events leading to profound hyper-inflammation. It is reasonable to infer that in deceased organ donors, death-induced hyperinflammation could have significant consequences for organs being offered for transplant. This systematic review aimed to; 1) clarify what is currently known about the sources of inflammation following death, and 2) systematically review the current body of evidence reporting levels of inflammation in deceased donors and living donors and linking donor inflammation with kidney transplant outcome. The systematic review was conducted in agreement with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines 8. We searched the Medline, Web of Science, Scopus and CINHAL databases from January 2000 to March 2023 for articles relating donor inflammation with kidney transplant outcomes. The National Institute of Health ‘Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies’ was used to assess validity of studies. Twenty-one studies were analysed, collectively totalling 3397 donors and 4596 recipients. A high degree of heterogeneity in inflammatory markers and transplant outcomes studied existed between studies, yet collective evidence showed higher inflammation, complement activation, and tissue injury in deceased donors compared with living donors, and strongly suggested associations with poorer short- and long-term transplant outcomes.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"40 1","pages":"Article 100980"},"PeriodicalIF":3.6,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145727891","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 : 2025-11-29DOI: 10.1016/j.trre.2025.100979
Yalong Zhang , Rui Yan , Hao Wang , Kangyu Wang , Jiangwei Man , Li Yang
With the widespread use of immunosuppressants and improved post-transplant survival, cryptococcosis has become a consequential opportunistic infection in kidney transplant recipients. This review synthesizes recent advances in epidemiology, pathogenesis, clinical presentation, diagnostics, treatment, and prognosis. Kidney transplant–associated cryptococcosis often presents insidiously, is prone to central nervous system involvement, and carries substantial risks of mortality and allograft loss. The adoption of rapid cryptococcal antigen lateral flow assays, broader access to liposomal amphotericin B, and individualized adjustments of immunosuppression have improved outcomes; however, challenges persist, including relapse, drug toxicities, and immune reconstitution inflammatory syndrome. We summarize current evidence and outline priorities for research and clinical practice, aiming to support timely diagnosis and optimized, phase-based antifungal strategies in this high-risk population.
{"title":"Cryptococcosis in kidney transplant recipients: Pathogenesis, clinical challenges, and evolving therapeutic strategies","authors":"Yalong Zhang , Rui Yan , Hao Wang , Kangyu Wang , Jiangwei Man , Li Yang","doi":"10.1016/j.trre.2025.100979","DOIUrl":"10.1016/j.trre.2025.100979","url":null,"abstract":"<div><div>With the widespread use of immunosuppressants and improved post-transplant survival, cryptococcosis has become a consequential opportunistic infection in kidney transplant recipients. This review synthesizes recent advances in epidemiology, pathogenesis, clinical presentation, diagnostics, treatment, and prognosis. Kidney transplant–associated cryptococcosis often presents insidiously, is prone to central nervous system involvement, and carries substantial risks of mortality and allograft loss. The adoption of rapid cryptococcal antigen lateral flow assays, broader access to liposomal amphotericin B, and individualized adjustments of immunosuppression have improved outcomes; however, challenges persist, including relapse, drug toxicities, and immune reconstitution inflammatory syndrome. We summarize current evidence and outline priorities for research and clinical practice, aiming to support timely diagnosis and optimized, phase-based antifungal strategies in this high-risk population.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"40 1","pages":"Article 100979"},"PeriodicalIF":3.6,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145663228","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 : 2025-11-10DOI: 10.1016/j.trre.2025.100969
Kaixin Li , Trent Payne , Ross Francis , Ruth E. Hubbard , Emily H. Gordon
Introduction
Frailty is increasingly recognized among patients with advanced organ disease (AOD). Solid organ transplantation (SOT) improves survival rates of patients with AOD and also impacts frailty status. However, there is considerable heterogeneity in frailty changes post-SOT reported in the literature. This study aims to determine whether the type of frailty tool contributes to heterogeneity in frailty outcomes after transplantation.
Methods
We searched PubMed, Embase, MEDLINE, Scopus, and Web of Science up to 1 August 2025 for studies assessing frailty before and after SOT in adults. Frailty tools were classified as phenotypic or deficit accumulation tools. Meta-analyses were conducted on baseline prevalence and changes in prevalence, with subgroup analyses by tool type and organ type. Narrative synthesis described changes in frailty scores, state transitions, and domain-specific outcomes across early, intermediate, and late post-transplant stages.
Results
Forteen studies (n = 3443) were included. Overall, phenotypic tools consistently captured reductions in frailty prevalence during the intermediate stage (6–12 months) post-transplant (mean difference, MD: −0.09; 95 % CI: −0.12 to −0.07; I2 = 0 %). In contrast, studies using deficit accumulation tools showed inconsistent results with high heterogeneity (MD: −0.19; 95 % CI: −1.18 to 0.79; I2 = 96.9 %). The organ-specific subgroup analysis revealed substantial heterogeneity within organ groups. Improvements in frailty scores and transitions to non-frail states were more frequently observed with the phenotypic tools with physical domains such as grip strength and activity improvement, while some deficit accumulation tools demonstrated deterioration.
Conclusions
Phenotypic frailty tools consistently detect improvements during intermediate post-SOT recovery, while deficit accumulation tools yield variable findings, highlighting the importance of appropriate frailty tool choice.
{"title":"A systematic review of frailty changes following solid organ transplantation: Is it all about the frailty tool?","authors":"Kaixin Li , Trent Payne , Ross Francis , Ruth E. Hubbard , Emily H. Gordon","doi":"10.1016/j.trre.2025.100969","DOIUrl":"10.1016/j.trre.2025.100969","url":null,"abstract":"<div><h3>Introduction</h3><div>Frailty is increasingly recognized among patients with advanced organ disease (AOD). Solid organ transplantation (SOT) improves survival rates of patients with AOD and also impacts frailty status. However, there is considerable heterogeneity in frailty changes post-SOT reported in the literature. This study aims to determine whether the type of frailty tool contributes to heterogeneity in frailty outcomes after transplantation.</div></div><div><h3>Methods</h3><div>We searched PubMed, Embase, MEDLINE, Scopus, and Web of Science up to 1 August 2025 for studies assessing frailty before and after SOT in adults. Frailty tools were classified as phenotypic or deficit accumulation tools. Meta-analyses were conducted on baseline prevalence and changes in prevalence, with subgroup analyses by tool type and organ type. Narrative synthesis described changes in frailty scores, state transitions, and domain-specific outcomes across early, intermediate, and late post-transplant stages.</div></div><div><h3>Results</h3><div>Forteen studies (<em>n</em> = 3443) were included. Overall, phenotypic tools consistently captured reductions in frailty prevalence during the intermediate stage (6–12 months) post-transplant (mean difference, MD: −0.09; 95 % CI: −0.12 to −0.07; I<sup>2</sup> = 0 %). In contrast, studies using deficit accumulation tools showed inconsistent results with high heterogeneity (MD: −0.19; 95 % CI: −1.18 to 0.79; I<sup>2</sup> = 96.9 %). The organ-specific subgroup analysis revealed substantial heterogeneity within organ groups. Improvements in frailty scores and transitions to non-frail states were more frequently observed with the phenotypic tools with physical domains such as grip strength and activity improvement, while some deficit accumulation tools demonstrated deterioration.</div></div><div><h3>Conclusions</h3><div>Phenotypic frailty tools consistently detect improvements during intermediate post-SOT recovery, while deficit accumulation tools yield variable findings, highlighting the importance of appropriate frailty tool choice.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"40 1","pages":"Article 100969"},"PeriodicalIF":3.6,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145544847","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}
Late-onset Pneumocystis jirovecii pneumonia (PCP) is increasingly recognized in kidney transplant recipients (KTRs) despite widespread prophylaxis. However, its prevalence and risk factors remain unclear.
Methods
We systematically searched electronic databases for studies published up to May 1, 2025, that reported prevalence or risk factors of late-onset PCP. Pooled prevalence, weighted mean differences (WMDs), and pooled odds ratios (ORs) were synthesized using a random-effects model.
Results
Of 1448 studies screened, 24 met inclusion criteria, comprising 57,662 KTRs, of whom 556 developed late-onset PCP. The pooled prevalence was 1.28 % (95 %CI 0.90–1.65). Lymphocyte counts were significantly lower in the infection group (WMD –408.34 cells/μL; 95 %CI –706.03 to −110.66). Risk was significantly increased with ABO-incompatible transplantation (OR 4.12; 95 %CI 1.04–16.30), rituximab induction (OR 4.77; 95 %CI, 1.50–15.21), corticosteroid (OR 2.56; 95 %CI 1.00–6.52) or mammalian target of rapamycin inhibitor (mTORi) maintenance (OR 2.37; 95 %CI 1.27–4.42), CMV infection (OR 5.21; 95 %CI 2.45–11.10), and rejection episodes (OR 2.93; 95 %CI 1.72–4.99), particularly when treated with plasma exchange, intravenous methylprednisolone, or rituximab. In contrast, cotrimoxazole prophylaxis reduced risk (OR 0.06; 95 %CI 0.01–0.60). Late-onset PCP was associated with graft loss (OR 6.11; 95 %CI 2.98–12.55) and mortality (OR 10.48; 95 %CI 1.92–57.16).
Conclusions
Although uncommon, late-onset PCP in KTRs is strongly linked with ABO-incompatible transplantation, lack of cotrimoxazole prophylaxis, lymphopenia, CMV infection, corticosteroid and mTORi, and rejection. KTRs with these high-risk features, including those receiving mTORi and corticosteroid maintenance, should be considered for prolonged or life-long PCP prophylaxis.
背景：迟发性肺囊虫肺炎（PCP）越来越多地在肾移植受者（KTRs）中得到认可，尽管广泛的预防。然而，其流行程度和危险因素仍不清楚。方法：我们系统地检索了电子数据库中截至2025年5月1日发表的关于迟发性PCP患病率或危险因素的研究。合并患病率、加权平均差异（wmd）和合并优势比（ORs）采用随机效应模型进行综合。结果：在筛选的1448项研究中，24项符合纳入标准，包括57,662例ktr，其中556例发展为晚发性PCP。合并患病率为1.28% （95% CI 0.90-1.65）。感染组淋巴细胞计数明显降低（WMD为-408.34 cells/μL； 95% CI为-706.03 ~ -110.66）。abo血型不相容移植（OR 4.12; 95% CI 1.04-16.30）、利妥昔单抗诱导（OR 4.77; 95% CI 1.50-15.21）、皮质类固醇（OR 2.56; 95% CI 1.00-6.52）或哺乳动物雷帕霉素靶抑制剂（mTORi）维持（OR 2.37; 95% CI 1.27-4.42）、巨细胞病毒感染（OR 5.21; 95% CI 2.45-11.10）和排斥事件（OR 2.93; 95% CI 1.72-4.99），尤其是当接受血浆交换、静脉注射甲基泼尼松龙或利妥昔单抗治疗时，风险显著增加。相反，复方新诺明预防可降低风险（OR 0.06; 95% CI 0.01-0.60）。晚发性PCP与移植物丢失（OR 6.11; 95% CI 2.98-12.55）和死亡率（OR 10.48; 95% CI 1.92-57.16）相关。结论：虽然不常见，但KTRs的晚发性PCP与abo血型不相容移植、缺乏复方新诺明预防、淋巴细胞减少、巨细胞病毒感染、皮质类固醇和mTORi以及排斥反应密切相关。具有这些高风险特征的ktr患者，包括那些接受mTORi和皮质类固醇维持治疗的患者，应考虑长期或终身预防PCP。
{"title":"Late-onset pneumocystis pneumonia after kidney transplantation: A systematic review and meta-analysis of prevalence, risk factors, and outcomes","authors":"Sirihatai Konwai , Chanyanuch Rakpithayanon , Thunyatorn Wuttiputhanun , Asada Leelahavanichkul , Natavudh Townamchai , Jakapat Vanichanan , Kamonwan Jutivorakool , Yingyos Avihingsanon , Kearkiat Praditpornsilpa , Suwasin Udomkarnjananun","doi":"10.1016/j.trre.2025.100972","DOIUrl":"10.1016/j.trre.2025.100972","url":null,"abstract":"<div><h3>Background</h3><div>Late-onset <em>Pneumocystis jirovecii</em> pneumonia (PCP) is increasingly recognized in kidney transplant recipients (KTRs) despite widespread prophylaxis. However, its prevalence and risk factors remain unclear.</div></div><div><h3>Methods</h3><div>We systematically searched electronic databases for studies published up to May 1, 2025, that reported prevalence or risk factors of late-onset PCP. Pooled prevalence, weighted mean differences (WMDs), and pooled odds ratios (ORs) were synthesized using a random-effects model.</div></div><div><h3>Results</h3><div>Of 1448 studies screened, 24 met inclusion criteria, comprising 57,662 KTRs, of whom 556 developed late-onset PCP. The pooled prevalence was 1.28 % (95 %CI 0.90–1.65). Lymphocyte counts were significantly lower in the infection group (WMD –408.34 cells/μL; 95 %CI –706.03 to −110.66). Risk was significantly increased with ABO-incompatible transplantation (OR 4.12; 95 %CI 1.04–16.30), rituximab induction (OR 4.77; 95 %CI, 1.50–15.21), corticosteroid (OR 2.56; 95 %CI 1.00–6.52) or mammalian target of rapamycin inhibitor (mTORi) maintenance (OR 2.37; 95 %CI 1.27–4.42), CMV infection (OR 5.21; 95 %CI 2.45–11.10), and rejection episodes (OR 2.93; 95 %CI 1.72–4.99), particularly when treated with plasma exchange, intravenous methylprednisolone, or rituximab. In contrast, cotrimoxazole prophylaxis reduced risk (OR 0.06; 95 %CI 0.01–0.60). Late-onset PCP was associated with graft loss (OR 6.11; 95 %CI 2.98–12.55) and mortality (OR 10.48; 95 %CI 1.92–57.16).</div></div><div><h3>Conclusions</h3><div>Although uncommon, late-onset PCP in KTRs is strongly linked with ABO-incompatible transplantation, lack of cotrimoxazole prophylaxis, lymphopenia, CMV infection, corticosteroid and mTORi, and rejection. KTRs with these high-risk features, including those receiving mTORi and corticosteroid maintenance, should be considered for prolonged or life-long PCP prophylaxis.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"40 1","pages":"Article 100972"},"PeriodicalIF":3.6,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145491378","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 : 2025-11-03DOI: 10.1016/j.trre.2025.100971
Michael Corr , Nawal Khan , Dessi Malinova , Alexander P. Maxwell , Gareth J. McKay , Matthew D. Griffin
Kidney transplantation provides the best survival advantage for children, adolescents, and young adults with end-stage kidney disease, yet this group paradoxically experiences the poorest long-term graft survival. Immune-mediated rejection is the predominant cause, but the cellular mechanisms that underpin this age-related disparity remain incompletely defined. This review synthesises current evidence on the impact of immune ageing across adaptive and innate compartments, focusing on T cells, B cells, and natural killer (NK) cells. In younger recipients, a large naïve T- and B-cell pool, robust thymic output, and efficient germinal centre activity confer heightened alloimmune reactivity, driving increased risk of acute cellular and antibody-mediated rejection. In contrast, older recipients exhibit features of immunosenescence, including loss of CD28 expression, accumulation of terminally differentiated effector subsets, impaired germinal centre responses, and attenuated NK cytotoxicity, resulting in diminished capacity to mount de novo responses but greater vulnerability to infection. These immune trajectories have direct clinical implications: younger recipients may require intensified, mechanism-targeted immunosuppression, whereas older recipients may be more amenable to minimisation or tolerance protocols. We further highlight emerging evidence for premature immunosenescence in paediatric dialysis populations, the contribution of age-associated B cells and NK subsets, and the role of immunophenotype-guided therapeutic strategies. Current uniform immunosuppression protocols inadequately account for developmental and age-related immune heterogeneity. We argue for an age- and immune phenotype–informed approach to therapy, integrating longitudinal immune profiling, biomarker development, and systems immunology to improve risk stratification, promote tolerance, and ultimately extend allograft survival across all age groups.
{"title":"Immune cell subsets in young kidney transplant recipients: Mechanistic and clinical perspectives","authors":"Michael Corr , Nawal Khan , Dessi Malinova , Alexander P. Maxwell , Gareth J. McKay , Matthew D. Griffin","doi":"10.1016/j.trre.2025.100971","DOIUrl":"10.1016/j.trre.2025.100971","url":null,"abstract":"<div><div>Kidney transplantation provides the best survival advantage for children, adolescents, and young adults with end-stage kidney disease, yet this group paradoxically experiences the poorest long-term graft survival. Immune-mediated rejection is the predominant cause, but the cellular mechanisms that underpin this age-related disparity remain incompletely defined. This review synthesises current evidence on the impact of immune ageing across adaptive and innate compartments, focusing on T cells, B cells, and natural killer (NK) cells. In younger recipients, a large naïve T- and B-cell pool, robust thymic output, and efficient germinal centre activity confer heightened alloimmune reactivity, driving increased risk of acute cellular and antibody-mediated rejection. In contrast, older recipients exhibit features of immunosenescence, including loss of CD28 expression, accumulation of terminally differentiated effector subsets, impaired germinal centre responses, and attenuated NK cytotoxicity, resulting in diminished capacity to mount de novo responses but greater vulnerability to infection. These immune trajectories have direct clinical implications: younger recipients may require intensified, mechanism-targeted immunosuppression, whereas older recipients may be more amenable to minimisation or tolerance protocols. We further highlight emerging evidence for premature immunosenescence in paediatric dialysis populations, the contribution of age-associated B cells and NK subsets, and the role of immunophenotype-guided therapeutic strategies. Current uniform immunosuppression protocols inadequately account for developmental and age-related immune heterogeneity. We argue for an age- and immune phenotype–informed approach to therapy, integrating longitudinal immune profiling, biomarker development, and systems immunology to improve risk stratification, promote tolerance, and ultimately extend allograft survival across all age groups.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"40 1","pages":"Article 100971"},"PeriodicalIF":3.6,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145442533","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 : 2025-11-02DOI: 10.1016/j.trre.2025.100970
Kristen D. Belfield , Krysta Walter , Jennifer E. Marvin , Ryan W. Bonner , Rebecca B. Carlson , Kristen R. Szempruch
Introduction
Current methods of estimating glomerular filtration rate (eGFR) are commonly based on serum creatinine (SCr); however, cystatin C (CysC)-based methods have recently become more available with increased uptake of CysC testing. Currently, there is a gap in literature reviewing the use of CysC in non-kidney transplant recipients. The aim of this literature review is to evaluate the use of CysC in the assessment of GFR in non-kidney transplant recipients.
Methods
Electronic databases Embase, PubMed, Cumulative Index for Nursing and Allied Health Literature, ClinicalTrials.gov, and EU Clinical Trials Register were searched.
Results
Of the 487 unique citations, 11 were included (eight liver, two lung, and one heart transplant). Five liver transplant studies found a better prognostic parameter or correlation to measured GFR with CysC based equations, and two liver and two lung transplant studies found the combined Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFRSCr-CysC equation demonstrated higher correlation, accuracy, or performance than with either SCr or CysC-based equations.
Conclusion
The inclusion of CysC-based eGFR measurements, in particular the 2012 and 2021 CKD-EPI eGFRSCr-CysC equation, for GFR assessment overall correlated with the control assessments more than its comparators in non-kidney transplant recipients while maintaining accuracy.
目前估计肾小球滤过率（eGFR）的方法通常基于血清肌酐（SCr）；然而，基于胱抑素C （CysC）的方法最近随着CysC检测的增加而变得更加可行。目前，关于CysC在非肾移植受者中的应用的文献综述存在空白。本文献综述的目的是评估CysC在评估非肾移植受者GFR中的应用。方法检索Embase、PubMed、Nursing and Allied Health Literature Cumulative Index、ClinicalTrials.gov和EU ClinicalTrials Register等电子数据库。结果487例文献引用中，有11例文献被引用（8例肝移植，2例肺移植，1例心脏移植）。五项肝移植研究发现基于CysC的方程与测量的GFR有更好的预后参数或相关性，两项肝和两项肺移植研究发现慢性肾脏疾病流行病学合作（CKD-EPI）联合egfrcr -CysC方程比基于SCr或CysC的方程具有更高的相关性、准确性或性能。结论纳入基于cysc的eGFR测量，特别是2012年和2021年CKD-EPI egfrcr - cysc方程，用于GFR评估总体上与非肾移植受者对照评估的相关性大于其比较物，同时保持准确性。
{"title":"Use of cystatin C as a marker for estimated glomerular filtration rate in non-kidney transplant recipients","authors":"Kristen D. Belfield , Krysta Walter , Jennifer E. Marvin , Ryan W. Bonner , Rebecca B. Carlson , Kristen R. Szempruch","doi":"10.1016/j.trre.2025.100970","DOIUrl":"10.1016/j.trre.2025.100970","url":null,"abstract":"<div><h3>Introduction</h3><div>Current methods of estimating glomerular filtration rate (eGFR) are commonly based on serum creatinine (SCr); however, cystatin C (CysC)-based methods have recently become more available with increased uptake of CysC testing. Currently, there is a gap in literature reviewing the use of CysC in non-kidney transplant recipients. The aim of this literature review is to evaluate the use of CysC in the assessment of GFR in non-kidney transplant recipients.</div></div><div><h3>Methods</h3><div>Electronic databases Embase, PubMed, Cumulative Index for Nursing and Allied Health Literature, <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>, and EU Clinical Trials Register were searched.</div></div><div><h3>Results</h3><div>Of the 487 unique citations, 11 were included (eight liver, two lung, and one heart transplant). Five liver transplant studies found a better prognostic parameter or correlation to measured GFR with CysC based equations, and two liver and two lung transplant studies found the combined Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR<sub>SCr-CysC</sub> equation demonstrated higher correlation, accuracy, or performance than with either SCr or CysC-based equations.</div></div><div><h3>Conclusion</h3><div>The inclusion of CysC-based eGFR measurements, in particular the 2012 and 2021 CKD-EPI eGFR<sub>SCr-CysC</sub> equation, for GFR assessment overall correlated with the control assessments more than its comparators in non-kidney transplant recipients while maintaining accuracy.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"40 1","pages":"Article 100970"},"PeriodicalIF":3.6,"publicationDate":"2025-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145520974","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 : 2025-10-17DOI: 10.1016/j.trre.2025.100967
Jad Kassir , Kevin Kaulanjan , Marc Olivier Timsit , Sarah Drouin , Thomas Prudhomme , Romain Boissier , Lionel Badet , Xavier Matillon , Julien Branchereau , Emilien Seizilles de Mazancourt
Introduction
Simulation-based training is increasingly recognized as a cornerstone of surgical education, aiming to improve technical skills while reducing risks for patients. In kidney transplantation, however, simulation remains poorly explored, and the validity and educational value of available models are unclear.
Materials and methods
A systematic literature search was performed in PubMed, Embase, Cochrane Library, and Google Scholar from inception until December 31, 2024. Studies in English and French reporting on kidney transplantation simulators were included. Two independent reviewers screened titles, abstracts, and full texts, with disagreements resolved by discussion. Data were extracted on study design, simulator characteristics, validation methods, outcomes, and biases.
Results
The search identified 3343 records, of which 8 studies met the inclusion criteria. Three focused on robot-assisted transplantation and five on open transplantation. Most publications described the development or construction of simulators rather than their validation. Three studies evaluated participant satisfaction through questionnaires, and two assessed technical performance using validated rating scales. However, other domains of validity—including content, construct, concurrent, and predictive validity—as well as educational impact were not formally assessed in any study. Overall, the methodological quality was low, with small sample sizes, heterogeneous evaluation methods, and no comparators.
Conclusion
The literature on kidney transplantation simulators remains limited. Existing studies focus largely on describing model development rather than providing robust validation or demonstrating educational benefit. Future research should emphasize standardized validation frameworks and structured evaluation to define the role of simulators in transplantation training.
{"title":"A systematic review of simulators for kidney transplantation surgical training","authors":"Jad Kassir , Kevin Kaulanjan , Marc Olivier Timsit , Sarah Drouin , Thomas Prudhomme , Romain Boissier , Lionel Badet , Xavier Matillon , Julien Branchereau , Emilien Seizilles de Mazancourt","doi":"10.1016/j.trre.2025.100967","DOIUrl":"10.1016/j.trre.2025.100967","url":null,"abstract":"<div><h3>Introduction</h3><div>Simulation-based training is increasingly recognized as a cornerstone of surgical education, aiming to improve technical skills while reducing risks for patients. In kidney transplantation, however, simulation remains poorly explored, and the validity and educational value of available models are unclear.</div></div><div><h3>Materials and methods</h3><div>A systematic literature search was performed in PubMed, Embase, Cochrane Library, and Google Scholar from inception until December 31, 2024. Studies in English and French reporting on kidney transplantation simulators were included. Two independent reviewers screened titles, abstracts, and full texts, with disagreements resolved by discussion. Data were extracted on study design, simulator characteristics, validation methods, outcomes, and biases.</div></div><div><h3>Results</h3><div>The search identified 3343 records, of which 8 studies met the inclusion criteria. Three focused on robot-assisted transplantation and five on open transplantation. Most publications described the development or construction of simulators rather than their validation. Three studies evaluated participant satisfaction through questionnaires, and two assessed technical performance using validated rating scales. However, other domains of validity—including content, construct, concurrent, and predictive validity—as well as educational impact were not formally assessed in any study. Overall, the methodological quality was low, with small sample sizes, heterogeneous evaluation methods, and no comparators.</div></div><div><h3>Conclusion</h3><div>The literature on kidney transplantation simulators remains limited. Existing studies focus largely on describing model development rather than providing robust validation or demonstrating educational benefit. Future research should emphasize standardized validation frameworks and structured evaluation to define the role of simulators in transplantation training.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"39 4","pages":"Article 100967"},"PeriodicalIF":3.6,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319586","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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