Pub Date : 2024-08-23DOI: 10.1016/j.ajt.2024.08.016
Luckmini N Liyanage, Daniyar Akizhanov, Suhani S Patel, Dorry L Segev, Allan B Massie, Darren E Stewart, Sommer E Gentry
Since 2021, the OPTN has reported a nearly 10-fold rise in out-of-sequence (OOS) kidney allocation, generating concern and halting development of continuous distribution policies. We report contemporary (2022-2023) practice patterns in OOS allocation using OPTN data. We examined in sequence vs. OOS donors with multivariable logistic regression and skipped vs. OOS-accepting recipients with conditional logistic regression. Nearly 20% of kidney placements were OOS, varying from 0% to 43% across OPOs; the 5 highest-OOS OPOs accounted for 29% of all OOS. Of OOS kidneys, 33% were declined >100 times in the standard allocation sequence and 51% were declined by >10 centers before OOS allocation began; 4.5% were made without any in-sequence declines. Nearly all OOS offers were open offers. OOS kidneys were more likely to be from female, Black, older, DCD, hypertensive, diabetic, and elevated creatinine donors. Candidates receiving OOS kidneys were more likely female, Asian, and older than skipped candidates. Higher-volume centers and centers with more White, fewer Hispanic, and more educated waiting list patients transplanted disproportionately more OOS kidneys. These findings suggest that the current, highly variable, discretionary use of OOS might exacerbate disparities, yet the impact of OOS on organ utilization cannot be determined with data now collected.
{"title":"Contemporary Prevalence and Practice Patterns of Out-of-Sequence Kidney Allocation.","authors":"Luckmini N Liyanage, Daniyar Akizhanov, Suhani S Patel, Dorry L Segev, Allan B Massie, Darren E Stewart, Sommer E Gentry","doi":"10.1016/j.ajt.2024.08.016","DOIUrl":"https://doi.org/10.1016/j.ajt.2024.08.016","url":null,"abstract":"<p><p>Since 2021, the OPTN has reported a nearly 10-fold rise in out-of-sequence (OOS) kidney allocation, generating concern and halting development of continuous distribution policies. We report contemporary (2022-2023) practice patterns in OOS allocation using OPTN data. We examined in sequence vs. OOS donors with multivariable logistic regression and skipped vs. OOS-accepting recipients with conditional logistic regression. Nearly 20% of kidney placements were OOS, varying from 0% to 43% across OPOs; the 5 highest-OOS OPOs accounted for 29% of all OOS. Of OOS kidneys, 33% were declined >100 times in the standard allocation sequence and 51% were declined by >10 centers before OOS allocation began; 4.5% were made without any in-sequence declines. Nearly all OOS offers were open offers. OOS kidneys were more likely to be from female, Black, older, DCD, hypertensive, diabetic, and elevated creatinine donors. Candidates receiving OOS kidneys were more likely female, Asian, and older than skipped candidates. Higher-volume centers and centers with more White, fewer Hispanic, and more educated waiting list patients transplanted disproportionately more OOS kidneys. These findings suggest that the current, highly variable, discretionary use of OOS might exacerbate disparities, yet the impact of OOS on organ utilization cannot be determined with data now collected.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":null,"pages":null},"PeriodicalIF":8.9,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054231","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 : 2024-08-22DOI: 10.1016/j.ajt.2024.08.017
Li Xiao
{"title":"Regarding the novel scoring system to predict short-term mortality after living donor liver transplantation for acute liver failure.","authors":"Li Xiao","doi":"10.1016/j.ajt.2024.08.017","DOIUrl":"https://doi.org/10.1016/j.ajt.2024.08.017","url":null,"abstract":"","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":null,"pages":null},"PeriodicalIF":8.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054267","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 : 2024-08-21DOI: 10.1016/j.ajt.2024.08.008
Hye-Mee Kwon, Jae Hwan Kim, Sung-Hoon Kim, In-Gu Jun, Jun-Gol Song, Deok-Bog Moon, Gyu-Sam Hwang
We evaluated the liver transplantation (LT) criteria in acute-on-chronic liver failure (ACLF), incorporating an urgent living-donor LT (LDLT) program. Critically ill patients with a Chronic Liver Failure Consortium (CLIF-C) ACLF score (CLIF-C_ACLF_score) ≥65, previously considered unsuitable for LT, were included to explore the excess mortality threshold of the CLIF-C_ACLF_score (CLIF-C_ACLF_score_threshold). We followed 854 consecutive patients with ACLF (276 ACLF grade 2 and 215 ACLF grade 3) over 10 years among 4432 LT recipients between 2008 and 2019. For advanced ACLF patients without immediate deceased-donor (DD) allocation, an urgent LDLT program was expedited. The CLIF-C_ACLF_score_threshold was determined by the metrics of transplant survival benefit: >60% 1-year and >50% 5-year survival rate. In predicting post-LT mortality, the CLIF-C_ACLF_score outperformed the (model for end-stage liver disease-sodium) MELD-Na and (model for end-stage liver disease) MELD-3.0 scores but was comparable to the Sundaram ACLF-LT-mortality score. A CLIF-C_ACLF_score ≥65 (n = 54) demonstrated posttransplant survival benefits, with 1-year and 5-year survival rates of 66.7% and 50.4% (P < .001), respectively. Novel CLIF-C_ACLF_score_threshold for 1-year and 5-year mortalities was 70 and 69, respectively. A CLIF-C_ACLF_score-based nomogram for predicting survival probabilities, integrating cardiovascular disease, diabetes, and donor type (LDLT vs DDLT), was generated. This study suggests reconsidering the criteria for unsuitable LT with a CLIF-C_ACLF_score ≥65. Implementing a timely salvage LT strategy, and incorporating urgent LDLT, can enhance survival rates.
{"title":"Benefits of liver transplant in critically ill patients with acute-on-chronic liver failure: Implementation of an urgent living-donor program.","authors":"Hye-Mee Kwon, Jae Hwan Kim, Sung-Hoon Kim, In-Gu Jun, Jun-Gol Song, Deok-Bog Moon, Gyu-Sam Hwang","doi":"10.1016/j.ajt.2024.08.008","DOIUrl":"10.1016/j.ajt.2024.08.008","url":null,"abstract":"<p><p>We evaluated the liver transplantation (LT) criteria in acute-on-chronic liver failure (ACLF), incorporating an urgent living-donor LT (LDLT) program. Critically ill patients with a Chronic Liver Failure Consortium (CLIF-C) ACLF score (CLIF-C_ACLF_score) ≥65, previously considered unsuitable for LT, were included to explore the excess mortality threshold of the CLIF-C_ACLF_score (CLIF-C_ACLF_score_threshold). We followed 854 consecutive patients with ACLF (276 ACLF grade 2 and 215 ACLF grade 3) over 10 years among 4432 LT recipients between 2008 and 2019. For advanced ACLF patients without immediate deceased-donor (DD) allocation, an urgent LDLT program was expedited. The CLIF-C_ACLF_score_threshold was determined by the metrics of transplant survival benefit: >60% 1-year and >50% 5-year survival rate. In predicting post-LT mortality, the CLIF-C_ACLF_score outperformed the (model for end-stage liver disease-sodium) MELD-Na and (model for end-stage liver disease) MELD-3.0 scores but was comparable to the Sundaram ACLF-LT-mortality score. A CLIF-C_ACLF_score ≥65 (n = 54) demonstrated posttransplant survival benefits, with 1-year and 5-year survival rates of 66.7% and 50.4% (P < .001), respectively. Novel CLIF-C_ACLF_score_threshold for 1-year and 5-year mortalities was 70 and 69, respectively. A CLIF-C_ACLF_score-based nomogram for predicting survival probabilities, integrating cardiovascular disease, diabetes, and donor type (LDLT vs DDLT), was generated. This study suggests reconsidering the criteria for unsuitable LT with a CLIF-C_ACLF_score ≥65. Implementing a timely salvage LT strategy, and incorporating urgent LDLT, can enhance survival rates.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":null,"pages":null},"PeriodicalIF":8.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141998930","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 : 2024-08-18DOI: 10.1016/j.ajt.2024.08.011
Christian T J Magyar, Zhihao Li, Laia Aceituno, Marco P A W Claasen, Tommy Ivanics, Woo Jin Choi, Luckshi Rajendran, Blayne A Sayed, Roxana Bucur, Nadia Rukavina, Nazia Selzner, Anand Ghanekar, Mark Cattral, Gonzalo Sapisochin
Living donor liver transplantation (LDLT) is a curative treatment for various liver diseases, reducing waitlist times and associated mortality. We aimed to assess the overall survival (OS), identify predictors for mortality, and analyze differences in risk factors over time. Adult patients undergoing LDLT were selected from the United Network for Organ Sharing database from inception (1987) to 2023. The Kaplan-Meier method was used for analysis, and multivariable Cox proportional hazard models were conducted. In total, 7257 LDLT recipients with a median age of 54 years (interquartile range [IQR]: 45-61 years), 54% male, 80% non-Hispanic White, body mass index of 26.3 kg/m2 (IQR: 23.2-30.0 kg/m2), and model for end-stage liver disease score of 15 (IQR: 11-19) were included. The median cold ischemic time was 1.6 hours (IQR: 1.0-2.3 hours) with 88% right lobe grafts. The follow-up was 4.0 years (IQR: 1.0-9.2 years). The contemporary reached median OS was 17.0 years (95% CI: 16.1, 18.1 years), with the following OS estimates: 1 year 95%; 3 years 89%; 5 years 84%; 10 years 72%; 15 years 56%; and 20 years 43%. Nine independent factors associated with mortality were identified, with an independent improved OS in the recent time era (adjusted hazards ratio: 0.53; 95% CI: 0.39, 0.71). The median center-caseload per year was 5 (IQR: 2-10), with observed center-specific improvement of OS. LDLT is a safe procedure with excellent OS. Its efficacy has improved despite an increase of risk parameters, suggesting its limits are yet to be met.
{"title":"Temporal evolution of living donor liver transplantation survival-A United Network for Organ Sharing registry study.","authors":"Christian T J Magyar, Zhihao Li, Laia Aceituno, Marco P A W Claasen, Tommy Ivanics, Woo Jin Choi, Luckshi Rajendran, Blayne A Sayed, Roxana Bucur, Nadia Rukavina, Nazia Selzner, Anand Ghanekar, Mark Cattral, Gonzalo Sapisochin","doi":"10.1016/j.ajt.2024.08.011","DOIUrl":"10.1016/j.ajt.2024.08.011","url":null,"abstract":"<p><p>Living donor liver transplantation (LDLT) is a curative treatment for various liver diseases, reducing waitlist times and associated mortality. We aimed to assess the overall survival (OS), identify predictors for mortality, and analyze differences in risk factors over time. Adult patients undergoing LDLT were selected from the United Network for Organ Sharing database from inception (1987) to 2023. The Kaplan-Meier method was used for analysis, and multivariable Cox proportional hazard models were conducted. In total, 7257 LDLT recipients with a median age of 54 years (interquartile range [IQR]: 45-61 years), 54% male, 80% non-Hispanic White, body mass index of 26.3 kg/m<sup>2</sup> (IQR: 23.2-30.0 kg/m<sup>2</sup>), and model for end-stage liver disease score of 15 (IQR: 11-19) were included. The median cold ischemic time was 1.6 hours (IQR: 1.0-2.3 hours) with 88% right lobe grafts. The follow-up was 4.0 years (IQR: 1.0-9.2 years). The contemporary reached median OS was 17.0 years (95% CI: 16.1, 18.1 years), with the following OS estimates: 1 year 95%; 3 years 89%; 5 years 84%; 10 years 72%; 15 years 56%; and 20 years 43%. Nine independent factors associated with mortality were identified, with an independent improved OS in the recent time era (adjusted hazards ratio: 0.53; 95% CI: 0.39, 0.71). The median center-caseload per year was 5 (IQR: 2-10), with observed center-specific improvement of OS. LDLT is a safe procedure with excellent OS. Its efficacy has improved despite an increase of risk parameters, suggesting its limits are yet to be met.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":null,"pages":null},"PeriodicalIF":8.9,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142007900","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 : 2024-08-17DOI: 10.1016/j.ajt.2024.08.012
Al-Faraaz Kassam, David A Axelrod, Sunil K Geevarghese
Moral injury in healthcare is characterized as the lasting psychological, biological, and social impact on providers which occurs following an adverse patient outcome. Moral injury can contribute to second victim syndrome and lasting psychological harm. While many surgeons face moral injury due to patient acuity and the potential for intraoperative or post operative complications, the transplant ecosystem compounds the impact of moral injury. Institutional blame placed on the transplant surgeon following a post-transplant death or graft loss is magnified by public reporting. Centers whose outcomes fall below threshold levels are subject to regulatory citation and financial loss. Moral injury can also result in risk aversion, limiting access to transplant for higher risk candidates and reduced acceptance of marginal organs hurting donor families. Strategies to increase resilience, reduce accusation and blame, and focus on system quality improvement are vital to mitigate the impact of moral injury on transplant professionals. The transplant community must proactively work to reduce Moral Injury to protect surgeons, ensure access to life saving transplant procedures, and avoid unnecessary organ offer declines.
{"title":"Moral Injury: An Unspoken Burden of Transplant Surgery.","authors":"Al-Faraaz Kassam, David A Axelrod, Sunil K Geevarghese","doi":"10.1016/j.ajt.2024.08.012","DOIUrl":"https://doi.org/10.1016/j.ajt.2024.08.012","url":null,"abstract":"<p><p>Moral injury in healthcare is characterized as the lasting psychological, biological, and social impact on providers which occurs following an adverse patient outcome. Moral injury can contribute to second victim syndrome and lasting psychological harm. While many surgeons face moral injury due to patient acuity and the potential for intraoperative or post operative complications, the transplant ecosystem compounds the impact of moral injury. Institutional blame placed on the transplant surgeon following a post-transplant death or graft loss is magnified by public reporting. Centers whose outcomes fall below threshold levels are subject to regulatory citation and financial loss. Moral injury can also result in risk aversion, limiting access to transplant for higher risk candidates and reduced acceptance of marginal organs hurting donor families. Strategies to increase resilience, reduce accusation and blame, and focus on system quality improvement are vital to mitigate the impact of moral injury on transplant professionals. The transplant community must proactively work to reduce Moral Injury to protect surgeons, ensure access to life saving transplant procedures, and avoid unnecessary organ offer declines.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":null,"pages":null},"PeriodicalIF":8.9,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003152","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 : 2024-08-14DOI: 10.1016/j.ajt.2024.08.003
Amelie Kurnikowski, Espen Nordheim, Elisabeth Schwaiger, Simon Krenn, Jürgen Harreiter, Alexandra Kautzky-Willer, Michael Leutner, Johannes Werzowa, Andrea Tura, Klemens Budde, Kathrin Eller, Julio Pascual, Michael Krebs, Trond Geir Jenssen, Manfred Hecking
{"title":"Corrigendum to 'Criteria for prediabetes and posttransplant diabetes mellitus after kidney transplantation: A 2-year diagnostic accuracy study of participants from a randomized controlled trial' [American Journal of Transplantation 22 (2022)2880-2891].","authors":"Amelie Kurnikowski, Espen Nordheim, Elisabeth Schwaiger, Simon Krenn, Jürgen Harreiter, Alexandra Kautzky-Willer, Michael Leutner, Johannes Werzowa, Andrea Tura, Klemens Budde, Kathrin Eller, Julio Pascual, Michael Krebs, Trond Geir Jenssen, Manfred Hecking","doi":"10.1016/j.ajt.2024.08.003","DOIUrl":"https://doi.org/10.1016/j.ajt.2024.08.003","url":null,"abstract":"","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":null,"pages":null},"PeriodicalIF":8.9,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003151","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 : 2024-08-14DOI: 10.1016/j.ajt.2024.08.009
Manuel Luis Rodríguez-Perálvarez, Avik Majumdar, Emmanuel Tsochatzis
{"title":"Sex disparities in accessing liver transplantation: Biased renal function assessment is the main culprit.","authors":"Manuel Luis Rodríguez-Perálvarez, Avik Majumdar, Emmanuel Tsochatzis","doi":"10.1016/j.ajt.2024.08.009","DOIUrl":"10.1016/j.ajt.2024.08.009","url":null,"abstract":"","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":null,"pages":null},"PeriodicalIF":8.9,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141994811","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 : 2024-08-13DOI: 10.1016/j.ajt.2024.08.006
Inge Jonkman, Maaike M E Jacobs, Yutaka Negishi, Cansu Yanginlar, Joost H A Martens, Marijke Baltissen, Michiel Vermeulen, Martijn W F van den Hoogen, Marije Baas, Johan van der Vlag, Zahi A Fayad, Abraham J P Teunissen, Joren C Madsen, Jordi Ochando, Leo A B Joosten, Mihai G Netea, Willem J M Mulder, Musa M Mhlanga, Luuk B Hilbrands, Nils Rother, Raphaël Duivenvoorden
The innate immune system plays an essential role in regulating the immune responses to kidney transplantation, but the mechanisms through which innate immune cells influence long-term graft survival are unclear. The current study highlights the vital role of trained immunity in kidney allograft survival. Trained immunity describes the epigenetic and metabolic changes that innate immune cells undergo following an initial stimulus, allowing them have a stronger inflammatory response to subsequent stimuli. We stimulated healthy peripheral blood mononuclear cells with pretransplant and posttransplant serum of kidney transplant patients and immunosuppressive drugs in an in vitro trained immunity assay and measured tumor necrosis factor and interleukin 6 cytokine levels in the supernatant as a readout for trained immunity. We show that the serum of kidney transplant recipients collected 1 week after transplantation can suppress trained immunity. Importantly, we found that kidney transplant recipients whose serum most strongly suppressed trained immunity rarely experienced graft loss. This suppressive effect of posttransplant serum is likely mediated by previously unreported effects of immunosuppressive drugs. Our findings provide mechanistic insights into the role of innate immunity in kidney allograft survival, uncovering trained immunity as a potential therapeutic target for improving graft survival.
{"title":"Trained immunity suppression determines kidney allograft survival.","authors":"Inge Jonkman, Maaike M E Jacobs, Yutaka Negishi, Cansu Yanginlar, Joost H A Martens, Marijke Baltissen, Michiel Vermeulen, Martijn W F van den Hoogen, Marije Baas, Johan van der Vlag, Zahi A Fayad, Abraham J P Teunissen, Joren C Madsen, Jordi Ochando, Leo A B Joosten, Mihai G Netea, Willem J M Mulder, Musa M Mhlanga, Luuk B Hilbrands, Nils Rother, Raphaël Duivenvoorden","doi":"10.1016/j.ajt.2024.08.006","DOIUrl":"10.1016/j.ajt.2024.08.006","url":null,"abstract":"<p><p>The innate immune system plays an essential role in regulating the immune responses to kidney transplantation, but the mechanisms through which innate immune cells influence long-term graft survival are unclear. The current study highlights the vital role of trained immunity in kidney allograft survival. Trained immunity describes the epigenetic and metabolic changes that innate immune cells undergo following an initial stimulus, allowing them have a stronger inflammatory response to subsequent stimuli. We stimulated healthy peripheral blood mononuclear cells with pretransplant and posttransplant serum of kidney transplant patients and immunosuppressive drugs in an in vitro trained immunity assay and measured tumor necrosis factor and interleukin 6 cytokine levels in the supernatant as a readout for trained immunity. We show that the serum of kidney transplant recipients collected 1 week after transplantation can suppress trained immunity. Importantly, we found that kidney transplant recipients whose serum most strongly suppressed trained immunity rarely experienced graft loss. This suppressive effect of posttransplant serum is likely mediated by previously unreported effects of immunosuppressive drugs. Our findings provide mechanistic insights into the role of innate immunity in kidney allograft survival, uncovering trained immunity as a potential therapeutic target for improving graft survival.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":null,"pages":null},"PeriodicalIF":8.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141986955","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 : 2024-08-13DOI: 10.1016/j.ajt.2024.08.007
Allison J Kwong, Alina M Allen, Julie Heimbach
{"title":"Disparities in liver transplantation: One size may not fit all.","authors":"Allison J Kwong, Alina M Allen, Julie Heimbach","doi":"10.1016/j.ajt.2024.08.007","DOIUrl":"10.1016/j.ajt.2024.08.007","url":null,"abstract":"","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":null,"pages":null},"PeriodicalIF":8.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141986954","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 : 2024-08-12DOI: 10.1016/j.ajt.2024.08.005
Kathleen M Wragg, Matthew J Worley, Jane C Deng, Morgan Salmon, Daniel R Goldstein
Alterations in mitochondrial function and associated quality control programs, including mitochondrial-specific autophagy, termed mitophagy, are gaining increasing recognition in the context of disease. However, the role of mitophagy in organ transplant rejection remains poorly understood. Using mice deficient in Parkin, a ubiquitin ligase that tags damaged or dysfunctional mitochondria for autophagic clearance, we assessed the impact of Parkin-dependent mitophagy on skin-graft rejection. We observed accelerated graft loss in Parkin-deficient mice across multiple skin graft models. Immune cell distributions posttransplant were largely unperturbed compared to wild-type; however, the CD8+ T cells of Parkin-deficient mice expressed more T-bet, IFNγ, and Ki67, indicating greater priming toward effector function. This was accompanied by increased circulating levels of IL-12p70 in Parkin-deficient mice. Using a mixed leukocyte reaction, we demonstrated that naïve Parkin-deficient CD4+ and CD8+ T cells exhibit enhanced activation marker expression and proliferative responses to alloantigen, which were attenuated with administration of a pharmacological mitophagy inducer (p62-mediated mitophagy inducer), known to increase mitophagy in the absence of a functional PINK1-Parkin pathway. These findings indicate a role for Parkin-dependent mitophagy in curtailing skin-graft rejection.
{"title":"Deficiency in the mitophagy mediator Parkin accelerates murine skin allograft rejection.","authors":"Kathleen M Wragg, Matthew J Worley, Jane C Deng, Morgan Salmon, Daniel R Goldstein","doi":"10.1016/j.ajt.2024.08.005","DOIUrl":"10.1016/j.ajt.2024.08.005","url":null,"abstract":"<p><p>Alterations in mitochondrial function and associated quality control programs, including mitochondrial-specific autophagy, termed mitophagy, are gaining increasing recognition in the context of disease. However, the role of mitophagy in organ transplant rejection remains poorly understood. Using mice deficient in Parkin, a ubiquitin ligase that tags damaged or dysfunctional mitochondria for autophagic clearance, we assessed the impact of Parkin-dependent mitophagy on skin-graft rejection. We observed accelerated graft loss in Parkin-deficient mice across multiple skin graft models. Immune cell distributions posttransplant were largely unperturbed compared to wild-type; however, the CD8+ T cells of Parkin-deficient mice expressed more T-bet, IFNγ, and Ki67, indicating greater priming toward effector function. This was accompanied by increased circulating levels of IL-12p70 in Parkin-deficient mice. Using a mixed leukocyte reaction, we demonstrated that naïve Parkin-deficient CD4+ and CD8+ T cells exhibit enhanced activation marker expression and proliferative responses to alloantigen, which were attenuated with administration of a pharmacological mitophagy inducer (p62-mediated mitophagy inducer), known to increase mitophagy in the absence of a functional PINK1-Parkin pathway. These findings indicate a role for Parkin-dependent mitophagy in curtailing skin-graft rejection.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":null,"pages":null},"PeriodicalIF":8.9,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141981274","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}