Pub Date : 2024-09-25DOI: 10.1016/j.ajt.2024.09.029
Mia Wungnema,Madelaine Hack,Evgeniya Vaskova,Natali Gulbahce,Hao Zhang,Marica Grskovic,Allison Miller,Megan Stack,Angelo de Mattos,Phillipp W Raess,Wei Xie,Joanna Wiszniewska,Nicole K Andeen,Vanderlene L Kung,Erin Maynard,Shehzad Rehman
Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication of organ transplantation, commonly diagnosed after patients present with nonspecific constitutional symptoms and/or transplant organ dysfunction. Here we report a case of a kidney transplant recipient who was found to have highly elevated circulating donor-derived cell free DNA (dd-cfDNA) levels on routine serum surveillance for allograft rejection, initially without organ dysfunction or evidence of allograft rejection on biopsy. Later for cause imaging revealed retroperitoneal lymphadenopathy and an allograft hilar mass, which was biopsied to show post-transplant lymphoproliferative disorder/diffuse large B-cell lymphoma (DLBCL). The elevated circulating dd-cfDNA levels in this patient prompted targeted next-generation sequencing of the same 266 single-nucleotide polymorphisms used to detect dd-cfDNA on the DLBCL, which identified it as donor-derived. The patient achieved complete remission with retained allograft kidney function after reduced immunosuppression and 6 cycles of immunochemotherapy. This case suggests that dd-cfDNA may be an early detection tool in rare but potentially life-threatening cases of donor-derived malignancy, such as donor-derived PTLD.
{"title":"Donor-derived post-transplant lymphoproliferative disease detection by donor-derived cell free DNA.","authors":"Mia Wungnema,Madelaine Hack,Evgeniya Vaskova,Natali Gulbahce,Hao Zhang,Marica Grskovic,Allison Miller,Megan Stack,Angelo de Mattos,Phillipp W Raess,Wei Xie,Joanna Wiszniewska,Nicole K Andeen,Vanderlene L Kung,Erin Maynard,Shehzad Rehman","doi":"10.1016/j.ajt.2024.09.029","DOIUrl":"https://doi.org/10.1016/j.ajt.2024.09.029","url":null,"abstract":"Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication of organ transplantation, commonly diagnosed after patients present with nonspecific constitutional symptoms and/or transplant organ dysfunction. Here we report a case of a kidney transplant recipient who was found to have highly elevated circulating donor-derived cell free DNA (dd-cfDNA) levels on routine serum surveillance for allograft rejection, initially without organ dysfunction or evidence of allograft rejection on biopsy. Later for cause imaging revealed retroperitoneal lymphadenopathy and an allograft hilar mass, which was biopsied to show post-transplant lymphoproliferative disorder/diffuse large B-cell lymphoma (DLBCL). The elevated circulating dd-cfDNA levels in this patient prompted targeted next-generation sequencing of the same 266 single-nucleotide polymorphisms used to detect dd-cfDNA on the DLBCL, which identified it as donor-derived. The patient achieved complete remission with retained allograft kidney function after reduced immunosuppression and 6 cycles of immunochemotherapy. This case suggests that dd-cfDNA may be an early detection tool in rare but potentially life-threatening cases of donor-derived malignancy, such as donor-derived PTLD.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142329257","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}
Bartonella quintana (BQ) infection is rarely described to be transmitted through solid organ transplant (SOT). We report a cluster of donor-derived BQ infection and attack rate from Bartonella seropositive donors. Retrospective study of SOT recipients that received an organ from an unhoused deceased donor (UDD) in Alberta in 2022-2023. Serology testing for Bartonella was performed with Indirect Immunofluorescent Assay from UDD and recipients from UDD with positive serology. Titers ≥1:64 considered positive. During the study period, 31/32 UDD had IgG to Bartonella (20 negative, 11 positives (D+) for B.quintana and/or B.henselae). 32 organs were transplanted from 11D+. Six SOT recipients developed bartonellosis secondary to BQ (4 SOT received organs from 3 D+, and 2 SOT from 1 UDD with no stored sample for testing). The attack rate for clinical disease from D+ was of 12.5% (4/32). The main presentation: skin nodules/papules (median 5.5 months) with bacillary angiomatosis in 4/6. Bartonella serology was positive in 5/6 (initially negative in 2), blood BQ-qPCR in two. None had visceral involvement. All donors had history of substance use. This outbreak of bartonellosis reinforces the potential for unexpected donor transmitted infections. Clinicians should be aware of high transmission of BQ through transplant from infected UDD.
{"title":"Donor-derived bartonellosis in Solid Organ Transplant recipients from unhoused donors in Alberta.","authors":"Dima Kabbani,Efrat Orenbuch-Harroch,Carl Boodman,Sarah Broad,Manuel Paz-Infanzon,Sara Belga,Oscar A Fernández-García,Emily Christie,Majid Lingani Ncube Sikosana,Soroush Shojai,Sita Gourishankar,Carlos Cervera,Karen Doucette","doi":"10.1016/j.ajt.2024.09.026","DOIUrl":"https://doi.org/10.1016/j.ajt.2024.09.026","url":null,"abstract":"Bartonella quintana (BQ) infection is rarely described to be transmitted through solid organ transplant (SOT). We report a cluster of donor-derived BQ infection and attack rate from Bartonella seropositive donors. Retrospective study of SOT recipients that received an organ from an unhoused deceased donor (UDD) in Alberta in 2022-2023. Serology testing for Bartonella was performed with Indirect Immunofluorescent Assay from UDD and recipients from UDD with positive serology. Titers ≥1:64 considered positive. During the study period, 31/32 UDD had IgG to Bartonella (20 negative, 11 positives (D+) for B.quintana and/or B.henselae). 32 organs were transplanted from 11D+. Six SOT recipients developed bartonellosis secondary to BQ (4 SOT received organs from 3 D+, and 2 SOT from 1 UDD with no stored sample for testing). The attack rate for clinical disease from D+ was of 12.5% (4/32). The main presentation: skin nodules/papules (median 5.5 months) with bacillary angiomatosis in 4/6. Bartonella serology was positive in 5/6 (initially negative in 2), blood BQ-qPCR in two. None had visceral involvement. All donors had history of substance use. This outbreak of bartonellosis reinforces the potential for unexpected donor transmitted infections. Clinicians should be aware of high transmission of BQ through transplant from infected UDD.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328849","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 : 2024-09-24DOI: 10.1016/j.ajt.2024.09.023
Grace S Lee-Riddle,Carrie Thiessen,Brendan Parent,Aviva Goldberg,Jody L Jones,Elisa J Gordon
{"title":"Ethical considerations of conditional directed living donation - A North American perspective.","authors":"Grace S Lee-Riddle,Carrie Thiessen,Brendan Parent,Aviva Goldberg,Jody L Jones,Elisa J Gordon","doi":"10.1016/j.ajt.2024.09.023","DOIUrl":"https://doi.org/10.1016/j.ajt.2024.09.023","url":null,"abstract":"","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328846","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 : 2024-09-24DOI: 10.1016/j.ajt.2024.09.024
Teresa Brevini,Fotios Sampaziotis
{"title":"Time will tell: employing long term normothermic machine perfusion to gain new insight into bile duct regeneration.","authors":"Teresa Brevini,Fotios Sampaziotis","doi":"10.1016/j.ajt.2024.09.024","DOIUrl":"https://doi.org/10.1016/j.ajt.2024.09.024","url":null,"abstract":"","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328900","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 : 2024-09-24DOI: 10.1016/j.ajt.2024.09.021
Andrea Angeletti,Gianluca Caridi,Gian Marco Ghiggeri,Enrico E Verrina
{"title":"Reply to Randone et al - Rescue with Obinutuzumab and Daratumumab as Combined B-cell/Plasma Cell Targeting Approach in Severe Post-Transplant FSGS Recurrence.","authors":"Andrea Angeletti,Gianluca Caridi,Gian Marco Ghiggeri,Enrico E Verrina","doi":"10.1016/j.ajt.2024.09.021","DOIUrl":"https://doi.org/10.1016/j.ajt.2024.09.021","url":null,"abstract":"","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328847","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 : 2024-09-24DOI: 10.1016/j.ajt.2024.09.022
Joel T Adler,Sidharth Sharma
{"title":"Out of sequence allocation: a necessary innovation or a new inequity in transplantation?","authors":"Joel T Adler,Sidharth Sharma","doi":"10.1016/j.ajt.2024.09.022","DOIUrl":"https://doi.org/10.1016/j.ajt.2024.09.022","url":null,"abstract":"","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328848","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 : 2024-09-19DOI: 10.1016/j.ajt.2024.09.017
Timothy L Pruett,Susan M Wolf,Claire Colby McVan,Peter Lyon,Alexander M Capron,James F Childress,Barbara J Evans,Erik B Finger,Insoo Hyun,Rosario Isasi,Gary E Marchant,Andrew D Maynard,Kenneth A Oye,Mehmet Toner,Korkut Uygun,John C Bischof
Time limits on organ viability from retrieval to implantation shape the US system for human organ transplantation. Preclinical research has demonstrated that emerging biopreservation technologies can prolong organ viability, perhaps indefinitely. These technologies could transform transplantation into a scheduled procedure without geographic or time constraints, permitting organ assessment and potential preconditioning of the recipients. However, the safety and efficacy of advanced biopreservation with prolonged storage of vascularized organs followed by reanimation will require new regulatory oversight, as clinicians and transplant centers are not trained in the engineering techniques involved or equipped to assess the manipulated organs. Although the Food and Drug Administration is best situated to provide that process oversight, the agency has until now declined to oversee organ quality and has excluded vascularized organs from the oversight framework of HCT/Ps. Integration of advanced biopreservation technologies will require new facilities for organ preservation, storage, and reanimation plus ethical guidance on immediate organ use versus preservation, national allocation, and governance of centralized organ banks. Realization of the long-term benefit of advanced biopreservation requires anticipation of the necessary legal and ethical oversight tools and that process should begin now.
{"title":"Governing New Technologies that Stop Biological Time: Preparing for Prolonged Biopreservation of Human Organs in Transplantation.","authors":"Timothy L Pruett,Susan M Wolf,Claire Colby McVan,Peter Lyon,Alexander M Capron,James F Childress,Barbara J Evans,Erik B Finger,Insoo Hyun,Rosario Isasi,Gary E Marchant,Andrew D Maynard,Kenneth A Oye,Mehmet Toner,Korkut Uygun,John C Bischof","doi":"10.1016/j.ajt.2024.09.017","DOIUrl":"https://doi.org/10.1016/j.ajt.2024.09.017","url":null,"abstract":"Time limits on organ viability from retrieval to implantation shape the US system for human organ transplantation. Preclinical research has demonstrated that emerging biopreservation technologies can prolong organ viability, perhaps indefinitely. These technologies could transform transplantation into a scheduled procedure without geographic or time constraints, permitting organ assessment and potential preconditioning of the recipients. However, the safety and efficacy of advanced biopreservation with prolonged storage of vascularized organs followed by reanimation will require new regulatory oversight, as clinicians and transplant centers are not trained in the engineering techniques involved or equipped to assess the manipulated organs. Although the Food and Drug Administration is best situated to provide that process oversight, the agency has until now declined to oversee organ quality and has excluded vascularized organs from the oversight framework of HCT/Ps. Integration of advanced biopreservation technologies will require new facilities for organ preservation, storage, and reanimation plus ethical guidance on immediate organ use versus preservation, national allocation, and governance of centralized organ banks. Realization of the long-term benefit of advanced biopreservation requires anticipation of the necessary legal and ethical oversight tools and that process should begin now.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276907","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 : 2024-09-18DOI: 10.1016/j.ajt.2024.09.016
Jonathan de Fallois,Anna Günzel,Christoph Daniel,Julian Stumpf,Martin Busch,Ulrich Pein,Alexander Paliege,Kerstin Amann,Thorsten Wiech,Elena Hantmann,Gunter Wolf,Felix Pfeifer,Matthias Girndt,Tom H Lindner,Antje Weimann,Daniel Seehofer,Anette Bachmann,Klemens Budde,Ronald Biemann,Berend Isermann,Christoph Engel,Katalin Dittrich,Christian Hugo,Jan Halbritter
Predicting future kidney allograft function is challenging. Novel biomarkers, such as urinary Dickkopf-3 (uDKK3), may help guide donor selection and improve allograft outcomes. In this prospective multicenter pilot trial, we investigated whether donor uDKK3 reflects organ quality and is associated with future allograft function. We measured uDKK3/creatinine ratios (uDKK3/crea) from 95 deceased and 46 living kidney donors. Pre-nephrectomy uDKK3/crea levels were 100x higher in deceased than in living donors (9888 pg/mg versus 113 pg/mg, p<0.001). Among deceased donor transplantations, recipients were stratified by their corresponding uDKK3/crea donor levels ranging below (group A, n=68) or above (group B, n=65) median. The primary endpoint of best estimated glomerular filtration rate (eGFR) within the first 3 months after kidney transplantation was superior in group A (56.3 ml/min/1.73 m2) compared to group B (44.2 ml/min/1.73 m2, p=0.0139). Second, the composite clinical endpoint consisting of death, allograft failure or eGFR decline >50% occurred less frequent in group A. By mixed linear regression modelling, donor uDKK3/crea remained an independent predictor of eGFR after transplantation, with a slope of -4.282 ml/min/1.73 m2 per logarithmic increase in donor uDKK3/crea. In summary, urinary DKK3 may serve as a non-invasive, donor-dependent biomarker for assessing organ quality and future allograft function.
{"title":"Deceased donor urinary DKK3 associates with future allograft function following kidney transplantation.","authors":"Jonathan de Fallois,Anna Günzel,Christoph Daniel,Julian Stumpf,Martin Busch,Ulrich Pein,Alexander Paliege,Kerstin Amann,Thorsten Wiech,Elena Hantmann,Gunter Wolf,Felix Pfeifer,Matthias Girndt,Tom H Lindner,Antje Weimann,Daniel Seehofer,Anette Bachmann,Klemens Budde,Ronald Biemann,Berend Isermann,Christoph Engel,Katalin Dittrich,Christian Hugo,Jan Halbritter","doi":"10.1016/j.ajt.2024.09.016","DOIUrl":"https://doi.org/10.1016/j.ajt.2024.09.016","url":null,"abstract":"Predicting future kidney allograft function is challenging. Novel biomarkers, such as urinary Dickkopf-3 (uDKK3), may help guide donor selection and improve allograft outcomes. In this prospective multicenter pilot trial, we investigated whether donor uDKK3 reflects organ quality and is associated with future allograft function. We measured uDKK3/creatinine ratios (uDKK3/crea) from 95 deceased and 46 living kidney donors. Pre-nephrectomy uDKK3/crea levels were 100x higher in deceased than in living donors (9888 pg/mg versus 113 pg/mg, p<0.001). Among deceased donor transplantations, recipients were stratified by their corresponding uDKK3/crea donor levels ranging below (group A, n=68) or above (group B, n=65) median. The primary endpoint of best estimated glomerular filtration rate (eGFR) within the first 3 months after kidney transplantation was superior in group A (56.3 ml/min/1.73 m2) compared to group B (44.2 ml/min/1.73 m2, p=0.0139). Second, the composite clinical endpoint consisting of death, allograft failure or eGFR decline >50% occurred less frequent in group A. By mixed linear regression modelling, donor uDKK3/crea remained an independent predictor of eGFR after transplantation, with a slope of -4.282 ml/min/1.73 m2 per logarithmic increase in donor uDKK3/crea. In summary, urinary DKK3 may serve as a non-invasive, donor-dependent biomarker for assessing organ quality and future allograft function.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275227","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 : 2024-09-17DOI: 10.1016/j.ajt.2024.09.015
Sarah E Booker,Carlos Martinez,Laura A Cartwright,Katrina Gauntt,Joann White,Ty B Dunn,Oyedolamu Olaitan
{"title":"Pancreata recovered for research: Has the increase impacted pancreas transplantation?","authors":"Sarah E Booker,Carlos Martinez,Laura A Cartwright,Katrina Gauntt,Joann White,Ty B Dunn,Oyedolamu Olaitan","doi":"10.1016/j.ajt.2024.09.015","DOIUrl":"https://doi.org/10.1016/j.ajt.2024.09.015","url":null,"abstract":"","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142273386","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 : 2024-09-17DOI: 10.1016/j.ajt.2024.09.014
Sanjay Kulkarni,Keren Ladin
{"title":"Ethical Implications of Prioritizing Utility at all Costs: The Rise of Out-of-Sequence Transplants.","authors":"Sanjay Kulkarni,Keren Ladin","doi":"10.1016/j.ajt.2024.09.014","DOIUrl":"https://doi.org/10.1016/j.ajt.2024.09.014","url":null,"abstract":"","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142273388","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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