Pub Date : 2025-07-01Epub Date: 2025-05-05DOI: 10.1016/j.trre.2025.100935
L.H.M. Pengel , V. Mazarello-Paes , D. Paredes-Zapata , G.C. Oniscu , C. Gouveia Gaglianone , L. Zhu , Y. Wang , N. Dhanda , J. Tocher , L. Aviles
Healthcare professionals (HCPs) play an essential role in organ donation (OD) particularly when approaching families to discuss consent to OD. We synthesized the evidence on experiences of HCPs when approaching potential organ donor families. Fourteen electronic databases were searched to identify studies describing HCP experiences or associations between HCP experiences and consent rates. Methodological quality was assessed by independent reviewers using the Mixed Methods Appraisal Tool. Qualitative data were analysed using thematic synthesis, while quantitative data were summarized by narrative review. Ninety-two studies were included. HCP experiences were conceptualised as a paradox due to the challenges to negotiate the boundaries between life and death. Organisational and personal aspects broadly shape the experiences of professionals. Studies suggest that staff experiences can be improved by training and education, however, quantitative studies did not show a strong association between OD training and improved consent rates. The complexities of the family approach were evident in the variety of interactions between HCPs and the donor family, which may explain why there is no uniform approach across settings and countries. The review highlights the challenges faced by professionals when negotiating policy and practice and informs recommendations to support staff involved in the OD process worldwide.
{"title":"The experiences of clinical staff approaching families for organ donation consent: A systematic review and thematic synthesis of qualitative studies","authors":"L.H.M. Pengel , V. Mazarello-Paes , D. Paredes-Zapata , G.C. Oniscu , C. Gouveia Gaglianone , L. Zhu , Y. Wang , N. Dhanda , J. Tocher , L. Aviles","doi":"10.1016/j.trre.2025.100935","DOIUrl":"10.1016/j.trre.2025.100935","url":null,"abstract":"<div><div>Healthcare professionals (HCPs) play an essential role in organ donation (OD) particularly when approaching families to discuss consent to OD. We synthesized the evidence on experiences of HCPs when approaching potential organ donor families. Fourteen electronic databases were searched to identify studies describing HCP experiences or associations between HCP experiences and consent rates. Methodological quality was assessed by independent reviewers using the Mixed Methods Appraisal Tool. Qualitative data were analysed using thematic synthesis, while quantitative data were summarized by narrative review. Ninety-two studies were included. HCP experiences were conceptualised as a paradox due to the challenges to negotiate the boundaries between life and death. Organisational and personal aspects broadly shape the experiences of professionals. Studies suggest that staff experiences can be improved by training and education, however, quantitative studies did not show a strong association between OD training and improved consent rates. The complexities of the family approach were evident in the variety of interactions between HCPs and the donor family, which may explain why there is no uniform approach across settings and countries. The review highlights the challenges faced by professionals when negotiating policy and practice and informs recommendations to support staff involved in the OD process worldwide.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"39 3","pages":"Article 100935"},"PeriodicalIF":3.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143937927","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 : 2025-07-01Epub Date: 2025-04-23DOI: 10.1016/j.trre.2025.100933
Xiaohan Jin , Haoji Yan , Zengwei Yu , Jier Ma , Xiangyun Zheng , Weiyang Chen , Yaling Liu , Jiaze Li , Qiang Pu , Dong Tian
Background
Whether survival differs between urgent lung transplantation (ULTx) and standard lung transplantation (LTx) remains unclear. This systematic review and meta-analysis aimed to evaluate survival and other post-transplant outcomes between ULTx and standard LTx.
Methods
PubMed, Embase, and Cochrane Library were searched up to July 31, 2024 for relevant studies. A meta-analysis of baseline characteristics and postoperative outcomes was then performed, with subgroup analyses by study designs and indications. Overall survival (OS) was set as the primary outcome in this study. Risk ratio (RR), mean differences (MD) with 95 % confidence interval (CI) were assessed using fixed-effects or random-effects models.
Results
Nine studies with 934 ULTx and 2980 standard LTx patients were included. ULTx group exhibited lower donor PaO2/FiO2 (P = 0.03) and higher pre-operative life support use (P < 0.001) than standard LTx group. No statistical difference in waiting list mortality was found between groups (28.4 % vs. 12.6 %; P = 0.54). ULTx was associated with significantly lower 1-year, 3-year, and 5-year OS than standard LTx (70.2 % vs. 80.0 %, 57.7 % vs. 66.7 %, 46.5 % vs. 56.2 %; all P < 0.001). At each time point, about 10 % OS rate differences were found consistently. In most subgroups, ULTx was associated with worse outcomes, but no difference in OS was observed in cystic fibrosis (CF) patients.
Conclusions
ULTx reduces waiting list mortality in critical patients, but is associated with worse OS than standard LTx. ULTx may limit short-term survival rather than long-term survival compared with standard LTx.
背景急诊肺移植（ULTx）和标准肺移植（LTx）的存活率是否不同仍不清楚。本系统综述和荟萃分析旨在评估ULTx和标准LTx的存活率及其他移植后结果。方法检索了PubMed、Embase和Cochrane图书馆截至2024年7月31日的相关研究。然后对基线特征和术后结果进行了荟萃分析，并根据研究设计和适应症进行了亚组分析。本研究将总生存期（OS）作为主要结果。采用固定效应或随机效应模型评估了风险比（RR）、平均差异（MD）及 95% 置信区间（CI）。与标准 LTx 组相比，ULTx 组的供体 PaO2/FiO2 更低（P = 0.03），术前生命支持使用率更高（P < 0.001）。两组之间的候诊死亡率无统计学差异（28.4% vs. 12.6%；P = 0.54）。ULTx的1年、3年和5年OS明显低于标准LTx（70.2% vs. 80.0%、57.7% vs. 66.7%、46.5% vs. 56.2%；所有P均为0.001）。在每个时间点，OS率差异均在10%左右。在大多数亚组中，ULTx与较差的预后相关，但在囊性纤维化（CF）患者中未观察到OS差异。与标准LTx相比，ULTx可能会限制短期生存而非长期生存。
{"title":"Outcomes of urgent lung transplantation in critically ill patients versus standard lung transplantation: A systematic review and meta-analysis","authors":"Xiaohan Jin , Haoji Yan , Zengwei Yu , Jier Ma , Xiangyun Zheng , Weiyang Chen , Yaling Liu , Jiaze Li , Qiang Pu , Dong Tian","doi":"10.1016/j.trre.2025.100933","DOIUrl":"10.1016/j.trre.2025.100933","url":null,"abstract":"<div><h3>Background</h3><div>Whether survival differs between urgent lung transplantation (ULTx) and standard lung transplantation (LTx) remains unclear. This systematic review and meta-analysis aimed to evaluate survival and other post-transplant outcomes between ULTx and standard LTx.</div></div><div><h3>Methods</h3><div>PubMed, Embase, and Cochrane Library were searched up to July 31, 2024 for relevant studies. A meta-analysis of baseline characteristics and postoperative outcomes was then performed, with subgroup analyses by study designs and indications. Overall survival (OS) was set as the primary outcome in this study. Risk ratio (RR), mean differences (MD) with 95 % confidence interval (CI) were assessed using fixed-effects or random-effects models.</div></div><div><h3>Results</h3><div>Nine studies with 934 ULTx and 2980 standard LTx patients were included. ULTx group exhibited lower donor PaO<sub>2</sub>/FiO<sub>2</sub> (<em>P</em> = 0.03) and higher pre-operative life support use (<em>P</em> < 0.001) than standard LTx group. No statistical difference in waiting list mortality was found between groups (28.4 % vs. 12.6 %; <em>P</em> = 0.54). ULTx was associated with significantly lower 1-year, 3-year, and 5-year OS than standard LTx (70.2 % vs. 80.0 %, 57.7 % vs. 66.7 %, 46.5 % vs. 56.2 %; all <em>P</em> < 0.001). At each time point, about 10 % OS rate differences were found consistently. In most subgroups, ULTx was associated with worse outcomes, but no difference in OS was observed in cystic fibrosis (CF) patients.</div></div><div><h3>Conclusions</h3><div>ULTx reduces waiting list mortality in critical patients, but is associated with worse OS than standard LTx. ULTx may limit short-term survival rather than long-term survival compared with standard LTx.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"39 3","pages":"Article 100933"},"PeriodicalIF":3.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143873710","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}
Xenotransplantation is emerging as one of several potential solutions for addressing organ donor shortages, with significant progress bringing it closer to clinical application. However, challenges remain, particularly concerning complement system dysregulation caused by species differences, as well as xenoantigens and coagulopathy. Complement regulatory proteins expressed on endothelial cells of donor xenografts are less compatible with complement components in recipients. These difficulties contribute to hyperacute rejection, characterized by antibody-mediated complement activation that destroys the graft within 24 h. Moreover, because molecules are incompatible across different species, ischemia-reperfusion injury or infection can easily elicit complement activity via all three pathways, resulting in xenograft loss via complement-mediated vascular injury. Complement activity also stimulate innate and adaptive immune cells. To address this issue, genetic modifications in donor pigs and the development of novel medicines have been tested in preclinical models with promising results. Pigs modified to express human complement-regulating molecules such as CD46, CD55, and CD59 have shown longer kidney xenograft survivals over years in preclinical models with nonhuman primates, paving the way for clinical trials. Anti-complement component agents such as C1 esterase and C5 inhibitors have also been shown to increase xenograft survivals. This review examines the role of the complement system in kidney xenotransplantation, emphasizing new research and clinical trial advancements.
{"title":"Mechanism and regulation of the complement activity in kidney xenotransplantation","authors":"Takayuki Hirose , Kiyohiko Hotta , Ryo Otsuka , Ken-Ichiro Seino","doi":"10.1016/j.trre.2025.100931","DOIUrl":"10.1016/j.trre.2025.100931","url":null,"abstract":"<div><div>Xenotransplantation is emerging as one of several potential solutions for addressing organ donor shortages, with significant progress bringing it closer to clinical application. However, challenges remain, particularly concerning complement system dysregulation caused by species differences, as well as xenoantigens and coagulopathy. Complement regulatory proteins expressed on endothelial cells of donor xenografts are less compatible with complement components in recipients. These difficulties contribute to hyperacute rejection, characterized by antibody-mediated complement activation that destroys the graft within 24 h. Moreover, because molecules are incompatible across different species, ischemia-reperfusion injury or infection can easily elicit complement activity via all three pathways, resulting in xenograft loss via complement-mediated vascular injury. Complement activity also stimulate innate and adaptive immune cells. To address this issue, genetic modifications in donor pigs and the development of novel medicines have been tested in preclinical models with promising results. Pigs modified to express human complement-regulating molecules such as CD46, CD55, and CD59 have shown longer kidney xenograft survivals over years in preclinical models with nonhuman primates, paving the way for clinical trials. Anti-complement component agents such as C1 esterase and C5 inhibitors have also been shown to increase xenograft survivals. This review examines the role of the complement system in kidney xenotransplantation, emphasizing new research and clinical trial advancements.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"39 3","pages":"Article 100931"},"PeriodicalIF":3.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829632","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 : 2025-07-01Epub Date: 2025-05-28DOI: 10.1016/j.trre.2025.100938
Anh Le , Kathleen Gaudio , Alessia N. Paparella , Michael Sullivan , Mara McAdams-DeMarco , Marcelo Cantarovich , Shaifali Sandal
Background
Extensive literature has highlighted the psychological burden experienced by kidney transplant recipients (KTRs) and its association with adverse outcomes. Psychological resilience can serve as a measure of baseline vulnerability, and low resilience is associated with poor mental health. We aimed to synthesize the existing literature that has explored the concept of resilience in kidney transplantation.
Methods
A scoping review was conducted due to the anticipated heterogeneity of the literature. Any empirical study that measured resilience using a validated tool in KTRs was included. Resilience could be a variable, a predictor, or an outcome. All study designs were considered with no time restrictions.
Results
Of the 4525 titles and abstracts screened, 14 were eligible for inclusion. Sample sizes ranged from 10 to 505 KTRs. One study exclusively focused on developing and validating a resilience scale while others used existing tools. Three studies compared resilience between different populations and the results were heterogeneous: similar resilience between KTRs and dialysis/pre-KT patients (n = 2) and another reporting better resilience in KTRs (n = 1). A decline in resilience scores after pediatric-adult transition (n = 1) and 3 months post-transplant (n = 1) was reported. In terms of outcomes, higher resilience was associated with medication adherence (n = 1), lower frailty (n = 2), and lower risk of psychopathology (n = 2). Two of the three included studies reported improvements in resilience scores with an exercise program and a resilience-enhancing program.
Conclusions
Our review highlights that resilience is an underused and poorly explored construct in KTRs. We recommend explorative and interventional work as resilience is measurable and modifiable.
{"title":"Exploring the psychological construct of resilience in kidney transplantation: A scoping review","authors":"Anh Le , Kathleen Gaudio , Alessia N. Paparella , Michael Sullivan , Mara McAdams-DeMarco , Marcelo Cantarovich , Shaifali Sandal","doi":"10.1016/j.trre.2025.100938","DOIUrl":"10.1016/j.trre.2025.100938","url":null,"abstract":"<div><h3>Background</h3><div>Extensive literature has highlighted the psychological burden experienced by kidney transplant recipients (KTRs) and its association with adverse outcomes. Psychological resilience can serve as a measure of baseline vulnerability, and low resilience is associated with poor mental health. We aimed to synthesize the existing literature that has explored the concept of resilience in kidney transplantation.</div></div><div><h3>Methods</h3><div>A scoping review was conducted due to the anticipated heterogeneity of the literature. Any empirical study that measured resilience using a validated tool in KTRs was included. Resilience could be a variable, a predictor, or an outcome. All study designs were considered with no time restrictions.</div></div><div><h3>Results</h3><div>Of the 4525 titles and abstracts screened, 14 were eligible for inclusion. Sample sizes ranged from 10 to 505 KTRs. One study exclusively focused on developing and validating a resilience scale while others used existing tools. Three studies compared resilience between different populations and the results were heterogeneous: similar resilience between KTRs and dialysis/pre-KT patients (<em>n</em> = 2) and another reporting better resilience in KTRs (<em>n</em> = 1). A decline in resilience scores after pediatric-adult transition (n = 1) and 3 months post-transplant (n = 1) was reported. In terms of outcomes, higher resilience was associated with medication adherence (n = 1), lower frailty (n = 2), and lower risk of psychopathology (n = 2). Two of the three included studies reported improvements in resilience scores with an exercise program and a resilience-enhancing program.</div></div><div><h3>Conclusions</h3><div>Our review highlights that resilience is an underused and poorly explored construct in KTRs. We recommend explorative and interventional work as resilience is measurable and modifiable.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"39 3","pages":"Article 100938"},"PeriodicalIF":3.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144189954","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 : 2025-07-01Epub Date: 2025-04-03DOI: 10.1016/j.trre.2025.100919
Esther Mancebo , Fritz Diekmann , Eduard Palou , Carlos Vilches , Marta Crespo , Auxiliadora Mazuecos , José L. Caro , Josep M. Cruzado , David San Segundo , Manuel Muro , Jesús Ontañón , Antonia Álvarez , Oriol Bestard , Constantino Fernández , M. Francisca González , Antonio Nieto , Rocío Vega , Estela Paz-Artal , Elisabeth Coll , Amado Andrés , Beatriz Domínguez-Gil
Highly sensitized patients awaiting kidney transplantation face substantial challenges due to the presence of potential donor-specific anti-HLA antibodies (DSA). These antibodies increase the risk of antibody-mediated rejection (ABMR), but also complicate their access to HLA compatible transplantation. Although advancements in allocation priority programs, such as the Spanish Program for the Access of Highly Sensitized Patients to Kidney Transplantation (PATHI), have introduced virtual crossmatching (v-XM) to streamline compatibility assessments, patients with >99,5 % virtual panel reactive antibodies (vPRA) often remain on waiting lists for extended periods with minimal chances of receiving a transplant.
This article summarizes Spanish guidelines for a harmonized and comprehensive framework for the management of highly sensitized patients. These guidelines focus on strategies to facilitate transplantation in the presence of DSA, including a stepwise approach to delist HLA antigens, prioritizing those recognized as “less deleterious” antibodies, to expand transplant options while minimizing immunological risks. Conventional desensitization techniques are discussed, alongside the innovative use of imlifidase to enable transplants in particularly complex cases. Post-transplant monitoring protocols are also exposed, with a focus on early detection of antibody rebound and effective management of ABMR.
Ultimately, this resource offers clinicians a structured framework to navigate the intricate challenges of kidney transplantation in high-risk populations, aiming to enhance access to life-saving procedures and improve patient outcomes.
{"title":"Spanish guidelines for kidney transplantation in highly sensitized patients with donor-specific anti-HLA antibodies","authors":"Esther Mancebo , Fritz Diekmann , Eduard Palou , Carlos Vilches , Marta Crespo , Auxiliadora Mazuecos , José L. Caro , Josep M. Cruzado , David San Segundo , Manuel Muro , Jesús Ontañón , Antonia Álvarez , Oriol Bestard , Constantino Fernández , M. Francisca González , Antonio Nieto , Rocío Vega , Estela Paz-Artal , Elisabeth Coll , Amado Andrés , Beatriz Domínguez-Gil","doi":"10.1016/j.trre.2025.100919","DOIUrl":"10.1016/j.trre.2025.100919","url":null,"abstract":"<div><div>Highly sensitized patients awaiting kidney transplantation face substantial challenges due to the presence of potential donor-specific anti-HLA antibodies (DSA). These antibodies increase the risk of antibody-mediated rejection (ABMR), but also complicate their access to HLA compatible transplantation. Although advancements in allocation priority programs, such as the Spanish Program for the Access of Highly Sensitized Patients to Kidney Transplantation (PATHI), have introduced virtual crossmatching (v-XM) to streamline compatibility assessments, patients with >99,5 % virtual panel reactive antibodies (vPRA) often remain on waiting lists for extended periods with minimal chances of receiving a transplant.</div><div>This article summarizes Spanish guidelines for a harmonized and comprehensive framework for the management of highly sensitized patients. These guidelines focus on strategies to facilitate transplantation in the presence of DSA, including a stepwise approach to delist HLA antigens, prioritizing those recognized as “less deleterious” antibodies, to expand transplant options while minimizing immunological risks. Conventional desensitization techniques are discussed, alongside the innovative use of imlifidase to enable transplants in particularly complex cases. Post-transplant monitoring protocols are also exposed, with a focus on early detection of antibody rebound and effective management of ABMR.</div><div>Ultimately, this resource offers clinicians a structured framework to navigate the intricate challenges of kidney transplantation in high-risk populations, aiming to enhance access to life-saving procedures and improve patient outcomes.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"39 3","pages":"Article 100919"},"PeriodicalIF":3.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143808653","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 : 2025-04-08DOI: 10.1016/j.trre.2025.100930
Tanguy Lafont , Subhankar Mukhopadhyay , Sohani N. Dassanayake , Maria Hernández-Fuentes , Paramit Chowdhury , Theodoros Kassimatis
Acute rejection (AR) and interstitial fibrosis/tubular atrophy (IFTA) are significant complications of kidney transplantation that have a negative impact on renal graft lifespan. Kidney transplant monitoring is currently performed with the use of on nonspecific biomarkers (serum creatinine and proteinuria) which have significant limitations and detect AR and IFTA only after significant damage to the kidney has been done. Moreover, many transplant patients are found to have histological evidence of rejection despite a stable creatinine (subclinical rejection – SCR). The “gold standard” diagnostic test for AR and IFTA is the transplant biopsy that also comes with limitations and can have major complications; therefore, it is not an ideal test for routine graft monitoring. The use of novel non-invasive (blood and urine) and invasive (graft biopsy) biomarkers, partly driven by advances in omics technologies, can lead to earlier and more accurate detection of AR/SCR and IFTA and to improved graft monitoring. The identification of the immunological pathways of AR/IFTA may also enable the design of tailormade treatments. This minireview provides a state-of-the-art update on current evidence and limitations from key studies on non-invasive and invasive biomarkers of AR/SCR and IFTA and gives a perspective on their potential future implementation and the underlying challenges.
{"title":"Advances in biomarkers of acute allograft rejection and interstitial fibrosis/tubular atrophy in kidney transplantation; future perspective and challenges in clinical implementation","authors":"Tanguy Lafont , Subhankar Mukhopadhyay , Sohani N. Dassanayake , Maria Hernández-Fuentes , Paramit Chowdhury , Theodoros Kassimatis","doi":"10.1016/j.trre.2025.100930","DOIUrl":"10.1016/j.trre.2025.100930","url":null,"abstract":"<div><div>Acute rejection (AR) and interstitial fibrosis/tubular atrophy (IFTA) are significant complications of kidney transplantation that have a negative impact on renal graft lifespan. Kidney transplant monitoring is currently performed with the use of on nonspecific biomarkers (serum creatinine and proteinuria) which have significant limitations and detect AR and IFTA only after significant damage to the kidney has been done. Moreover, many transplant patients are found to have histological evidence of rejection despite a stable creatinine (subclinical rejection – SCR). The “gold standard” diagnostic test for AR and IFTA is the transplant biopsy that also comes with limitations and can have major complications; therefore, it is not an ideal test for routine graft monitoring. The use of novel non-invasive (blood and urine) and invasive (graft biopsy) biomarkers, partly driven by advances in omics technologies, can lead to earlier and more accurate detection of AR/SCR and IFTA and to improved graft monitoring. The identification of the immunological pathways of AR/IFTA may also enable the design of tailormade treatments. This minireview provides a state-of-the-art update on current evidence and limitations from key studies on non-invasive and invasive biomarkers of AR/SCR and IFTA and gives a perspective on their potential future implementation and the underlying challenges.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"39 3","pages":"Article 100930"},"PeriodicalIF":3.6,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143808654","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 : 2025-04-01Epub Date: 2025-01-09DOI: 10.1016/j.trre.2025.100909
Seokjoo Lee, Thomas H. Dohlman, Reza Dana
Immunology depends on maintaining a delicate balance within the human body, and disruptions can result in conditions such as autoimmune diseases, immunodeficiencies, and hypersensitivity reactions. This balance is especially crucial in transplantation immunology, where one of the primary challenges is preventing graft rejection. Such rejection can lead to organ failure, increased patient mortality, and higher healthcare costs due to the limited availability of donor tissues relative to patient needs. Xenotransplantation, like using porcine corneas for human transplants, offers a potential solution to the donor tissue shortage but faces substantial immunological rejection issues. To prevent rejection in both allo- and xenotransplantation, a deep understanding of how the body maintains immunological balance is essential, particularly since achieving tolerance to non-self tissues is considered the “holy grail” of the field. The cornea, the most frequently transplanted solid organ, has a high acceptance rate due to its immune-privileged status and serves as an ideal model for studying graft rejection mechanisms that disrupt tolerance. However, multiple immune pathways complicate our understanding of these mechanisms. This review examines the rejection mechanisms in corneal transplantation, identifying key cells involved and potential therapeutic strategies to induce and maintain immunological tolerance in both allo- and xenografts across various transplants.
{"title":"Immunology in corneal transplantation—From homeostasis to graft rejection","authors":"Seokjoo Lee, Thomas H. Dohlman, Reza Dana","doi":"10.1016/j.trre.2025.100909","DOIUrl":"10.1016/j.trre.2025.100909","url":null,"abstract":"<div><div>Immunology depends on maintaining a delicate balance within the human body, and disruptions can result in conditions such as autoimmune diseases, immunodeficiencies, and hypersensitivity reactions. This balance is especially crucial in transplantation immunology, where one of the primary challenges is preventing graft rejection. Such rejection can lead to organ failure, increased patient mortality, and higher healthcare costs due to the limited availability of donor tissues relative to patient needs. Xenotransplantation, like using porcine corneas for human transplants, offers a potential solution to the donor tissue shortage but faces substantial immunological rejection issues. To prevent rejection in both allo- and xenotransplantation, a deep understanding of how the body maintains immunological balance is essential, particularly since achieving tolerance to non-self tissues is considered the “holy grail” of the field. The cornea, the most frequently transplanted solid organ, has a high acceptance rate due to its immune-privileged status and serves as an ideal model for studying graft rejection mechanisms that disrupt tolerance. However, multiple immune pathways complicate our understanding of these mechanisms. This review examines the rejection mechanisms in corneal transplantation, identifying key cells involved and potential therapeutic strategies to induce and maintain immunological tolerance in both allo- and xenografts across various transplants.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"39 2","pages":"Article 100909"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974252","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 : 2025-04-01Epub Date: 2025-03-02DOI: 10.1016/j.trre.2025.100913
Quentin Perrier , Johan Noble , Sandrine Lablanche
Beta-cell replacement therapies, including islet and pancreas transplantation, offer promising results in term of glycemic control for patients with type 1 diabetes experiencing high glycemic variability and severe hypoglycemia. However, long-term insulin independence remains challenging due to progressive graft function decline. Immunosuppressive regimens, especially calcineurin inhibitors such as tacrolimus, are known to be diabetogenic, contributing to the paradox of impaired beta-cell function in a diabetes treatment setting. Recent studies have focused on CTLA4-Ig (e.g., belatacept) as a potential alternative to calcineurin inhibitors, showing promising results in preclinical and clinical models. This review summarizes key advancements and remaining challenges in CTLA4 applications for beta-cell replacement. First, genetic engineering approaches aiming for CTLA4 expression in islets demonstrated initial success in delaying rejection but remain hindered by immune escape and limited integration efficacy. Coating techniques and exogenous CTLA4-Ig administration offer simpler, albeit transient, immunosuppressive effects, which, combined with encapsulation technologies, can improve graft survival. In non-human primate models, islet transplantation with immunosuppressant regimen using CTLA4-Ig combined with agents such as sirolimus or anti-CD154 has shown extended insulin independence, though full immune tolerance remains elusive. A limited number of human studies using belatacept for beta-cell replacement indicate reduced HbA1c levels and avoidance of severe hypoglycemia, yet consistent absence of rejection remains unachieved. Future research on BCR with CTLA4-Ig should explore graft survival in human islets transplantation and refine immunosuppressive protocols to leverage CTLA4-Ig potential in improving long-term graft function, thus enhancing the sustainability of CTLA4-Ig in clinical beta-cell replacement approach.
{"title":"Transition from preclinical to clinical application of CTLA4-Ig co-stimulation blockage in beta-cell replacement therapy","authors":"Quentin Perrier , Johan Noble , Sandrine Lablanche","doi":"10.1016/j.trre.2025.100913","DOIUrl":"10.1016/j.trre.2025.100913","url":null,"abstract":"<div><div>Beta-cell replacement therapies, including islet and pancreas transplantation, offer promising results in term of glycemic control for patients with type 1 diabetes experiencing high glycemic variability and severe hypoglycemia. However, long-term insulin independence remains challenging due to progressive graft function decline. Immunosuppressive regimens, especially calcineurin inhibitors such as tacrolimus, are known to be diabetogenic, contributing to the paradox of impaired beta-cell function in a diabetes treatment setting. Recent studies have focused on CTLA4-Ig (e.g., belatacept) as a potential alternative to calcineurin inhibitors, showing promising results in preclinical and clinical models. This review summarizes key advancements and remaining challenges in CTLA4 applications for beta-cell replacement. First, genetic engineering approaches aiming for CTLA4 expression in islets demonstrated initial success in delaying rejection but remain hindered by immune escape and limited integration efficacy. Coating techniques and exogenous CTLA4-Ig administration offer simpler, albeit transient, immunosuppressive effects, which, combined with encapsulation technologies, can improve graft survival. In non-human primate models, islet transplantation with immunosuppressant regimen using CTLA4-Ig combined with agents such as sirolimus or anti-CD154 has shown extended insulin independence, though full immune tolerance remains elusive. A limited number of human studies using belatacept for beta-cell replacement indicate reduced HbA1c levels and avoidance of severe hypoglycemia, yet consistent absence of rejection remains unachieved. Future research on BCR with CTLA4-Ig should explore graft survival in human islets transplantation and refine immunosuppressive protocols to leverage CTLA4-Ig potential in improving long-term graft function, thus enhancing the sustainability of CTLA4-Ig in clinical beta-cell replacement approach.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"39 2","pages":"Article 100913"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143550224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-01Epub Date: 2025-03-09DOI: 10.1016/j.trre.2025.100914
Cavizshajan Skanthan , Emily Nguyen , Lakindu Somaweera , Madhumitha Rabindranath , Ani Orchanian-Cheff , Alexandra Viau-Trudel , Myriam Khalili , Olusegun Famure , S. Joseph Kim
Immunosuppressive drugs are used in the management of transplant patients to prevent organ rejection. However, immunosuppression can be associated with adverse effects such as infections and cancers. This study aimed to characterize the measures of cumulative immunosuppressive drug exposure (CIDE) used in the literature and their associated outcomes in transplant patients. A literature search was conducted in Ovid MEDLINE, Ovid EMBASE, Cochrane CENTRAL, and Cochrane Database of Systematic Reviews using search terms related to maintenance immunosuppressants and CIDE. Study risk of bias was assessed using the Quality in Prognostic Studies tool. Thirty-one articles were included in this qualitative synthesis. Sixteen articles (52 %) calculated the total dose of immunosuppression over the treatment period, while eight (26 %) used area-under-the-curve of trough level concentrations to quantify CIDE. Five (16 %) articles investigated time-weighted metrics of calcineurin inhibitors and four (13 %) used other metrics that could not be categorized into the previous groups. Most studies investigated CIDE with calcineurin inhibitors and used additive dosing methods. This approach was also popular with corticosteroids and multi-drug exposures. The variety of metrics used in the literature reveals a lack of standardization in the evaluation of CIDE and long-term outcomes. Future studies should validate these metrics for clinical application, especially pertaining to infectious outcomes.
{"title":"Assessing cumulative exposure to maintenance immunosuppressive drugs: Metrics, outcomes, and implications for transplant patients","authors":"Cavizshajan Skanthan , Emily Nguyen , Lakindu Somaweera , Madhumitha Rabindranath , Ani Orchanian-Cheff , Alexandra Viau-Trudel , Myriam Khalili , Olusegun Famure , S. Joseph Kim","doi":"10.1016/j.trre.2025.100914","DOIUrl":"10.1016/j.trre.2025.100914","url":null,"abstract":"<div><div>Immunosuppressive drugs are used in the management of transplant patients to prevent organ rejection. However, immunosuppression can be associated with adverse effects such as infections and cancers. This study aimed to characterize the measures of cumulative immunosuppressive drug exposure (CIDE) used in the literature and their associated outcomes in transplant patients. A literature search was conducted in Ovid MEDLINE, Ovid EMBASE, Cochrane CENTRAL, and Cochrane Database of Systematic Reviews using search terms related to maintenance immunosuppressants and CIDE. Study risk of bias was assessed using the Quality in Prognostic Studies tool. Thirty-one articles were included in this qualitative synthesis. Sixteen articles (52 %) calculated the total dose of immunosuppression over the treatment period, while eight (26 %) used area-under-the-curve of trough level concentrations to quantify CIDE. Five (16 %) articles investigated time-weighted metrics of calcineurin inhibitors and four (13 %) used other metrics that could not be categorized into the previous groups. Most studies investigated CIDE with calcineurin inhibitors and used additive dosing methods. This approach was also popular with corticosteroids and multi-drug exposures. The variety of metrics used in the literature reveals a lack of standardization in the evaluation of CIDE and long-term outcomes. Future studies should validate these metrics for clinical application, especially pertaining to infectious outcomes.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"39 2","pages":"Article 100914"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610460","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 : 2025-04-01Epub Date: 2025-02-16DOI: 10.1016/j.trre.2025.100912
Bader A. Alfares , Martijn V. Verhagen , Rudi A.J.O. Dierckx , Hubert P. van der Doef , Robbert J. de Haas , Reinoud P.H. Bokkers
Portal vein stenosis (PVS) is a relatively frequent vascular complication after pediatric liver transplantation (pLT) that may result in portal hypertension. The aim of this study was to provide an overview of various diagnostic methods and imaging criteria used to diagnose PVS and to report their diagnostic accuracy. Until August 2024, PubMed and Embase were searched for English-language manuscripts with >5 patients and radiologic features of PVS. Three investigators screened articles and extracted data. The risk of bias was assessed using QUADAS-2. Twenty studies were identified. Doppler ultrasound (DUS) was the most used imaging method, followed by computed tomography (CT) and digital subtraction angiography (DSA). In studies comparing DUS with other diagnostic modalities, an elevated peak systolic velocity (PSV) and velocity ratio (VR) emerged as reliable indicators of PVS. An anastomotic diameter of <3.5 mm showed the best diagnostic performance, with a sensitivity of 100 % and a specificity of 91.8 %. Although DUS is the preferred initial diagnostic tool due to its non-invasive nature, CT and DSA remain essential in cases where DUS findings are inconclusive or when more detailed vascular assessment is necessary. DSA also allows for simultaneous endovascular treatment, further enhancing its utility. This systematic review emphasizes the need for larger, prospective studies to directly compare the diagnostic performance of these imaging modalities and to establish more consistent and reliable criteria for diagnosing PVS after pLT.
门静脉狭窄（PVS）是小儿肝移植（pLT）后比较常见的血管并发症，可能导致门静脉高压。本研究旨在概述用于诊断 PVS 的各种诊断方法和成像标准，并报告其诊断准确性。在2024年8月之前，我们在PubMed和Embase上检索了有>5名患者和PVS放射学特征的英文稿件。三名研究人员筛选了文章并提取了数据。采用QUADAS-2评估偏倚风险。共确定了 20 项研究。多普勒超声（DUS）是最常用的成像方法，其次是计算机断层扫描（CT）和数字减影血管造影（DSA）。在比较 DUS 与其他诊断方法的研究中，峰值收缩速度（PSV）和速度比值（VR）升高成为 PVS 的可靠指标。吻合口直径为 3.5 毫米的诊断效果最佳，敏感性为 100%，特异性为 91.8%。尽管 DUS 因其非侵入性而成为首选的初步诊断工具，但在 DUS 结果不确定或需要进行更详细的血管评估时，CT 和 DSA 仍然是必不可少的。DSA 还可同时进行血管内治疗，进一步提高了其实用性。本系统综述强调有必要进行更大规模的前瞻性研究，以直接比较这些成像模式的诊断性能，并为 pLT 后 PVS 的诊断建立更一致、更可靠的标准。
{"title":"Diagnosing portal vein stenosis after pediatric liver transplantation: A systematic review","authors":"Bader A. Alfares , Martijn V. Verhagen , Rudi A.J.O. Dierckx , Hubert P. van der Doef , Robbert J. de Haas , Reinoud P.H. Bokkers","doi":"10.1016/j.trre.2025.100912","DOIUrl":"10.1016/j.trre.2025.100912","url":null,"abstract":"<div><div>Portal vein stenosis (PVS) is a relatively frequent vascular complication after pediatric liver transplantation (pLT) that may result in portal hypertension. The aim of this study was to provide an overview of various diagnostic methods and imaging criteria used to diagnose PVS and to report their diagnostic accuracy. Until August 2024, PubMed and Embase were searched for English-language manuscripts with >5 patients and radiologic features of PVS. Three investigators screened articles and extracted data. The risk of bias was assessed using QUADAS-2. Twenty studies were identified. Doppler ultrasound (DUS) was the most used imaging method, followed by computed tomography (CT) and digital subtraction angiography (DSA). In studies comparing DUS with other diagnostic modalities, an elevated peak systolic velocity (PSV) and velocity ratio (VR) emerged as reliable indicators of PVS. An anastomotic diameter of <3.5 mm showed the best diagnostic performance, with a sensitivity of 100 % and a specificity of 91.8 %. Although DUS is the preferred initial diagnostic tool due to its non-invasive nature, CT and DSA remain essential in cases where DUS findings are inconclusive or when more detailed vascular assessment is necessary. DSA also allows for simultaneous endovascular treatment, further enhancing its utility. This systematic review emphasizes the need for larger, prospective studies to directly compare the diagnostic performance of these imaging modalities and to establish more consistent and reliable criteria for diagnosing PVS after pLT.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"39 2","pages":"Article 100912"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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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