Pub Date : 2025-02-01DOI: 10.1016/j.ajt.2024.07.029
Maarten Coemans , Thuong Hien Tran , Bernd Döhler , Allan B. Massie , Geert Verbeke , Dorry L. Segev , Sommer E. Gentry , Maarten Naesens
Graft failure and recipient death with functioning graft are important competing outcomes after kidney transplantation. Risk prediction models typically censor for the competing outcome thereby overestimating the cumulative incidence. The magnitude of this overestimation is not well described in real-world transplant data. This retrospective cohort study analyzed data from the European Collaborative Transplant Study (n = 125 250) and from the American Scientific Registry of Transplant Recipients (n = 190 258). Separate cause-specific hazard models using donor and recipient age as continuous predictors were developed for graft failure and recipient death. The hazard of graft failure increased quadratically with increasing donor age and decreased decaying with increasing recipient age. The hazard of recipient death increased linearly with increasing donor and recipient age. The cumulative incidence overestimation due to competing risk-censoring was largest in high-risk populations for both outcomes (old donors/recipients), sometimes amounting to 8.4 and 18.8 percentage points for graft failure and recipient death, respectively. In our illustrative model for posttransplant risk prediction, the absolute risk of graft failure and death is overestimated when censoring for the competing event, mainly in older donors and recipients. Prediction models for absolute risks should treat graft failure and death as competing events.
{"title":"A competing risks model to estimate the risk of graft failure and patient death after kidney transplantation using continuous donor-recipient age combinations","authors":"Maarten Coemans , Thuong Hien Tran , Bernd Döhler , Allan B. Massie , Geert Verbeke , Dorry L. Segev , Sommer E. Gentry , Maarten Naesens","doi":"10.1016/j.ajt.2024.07.029","DOIUrl":"10.1016/j.ajt.2024.07.029","url":null,"abstract":"<div><div>Graft failure and recipient death with functioning graft are important competing outcomes after kidney transplantation. Risk prediction models typically censor for the competing outcome thereby overestimating the cumulative incidence. The magnitude of this overestimation is not well described in real-world transplant data. This retrospective cohort study analyzed data from the European Collaborative Transplant Study (n = 125 250) and from the American Scientific Registry of Transplant Recipients (n = 190 258). Separate cause-specific hazard models using donor and recipient age as continuous predictors were developed for graft failure and recipient death. The hazard of graft failure increased quadratically with increasing donor age and decreased decaying with increasing recipient age. The hazard of recipient death increased linearly with increasing donor and recipient age. The cumulative incidence overestimation due to competing risk-censoring was largest in high-risk populations for both outcomes (old donors/recipients), sometimes amounting to 8.4 and 18.8 percentage points for graft failure and recipient death, respectively. In our illustrative model for posttransplant risk prediction, the absolute risk of graft failure and death is overestimated when censoring for the competing event, mainly in older donors and recipients. Prediction models for absolute risks should treat graft failure and death as competing events.</div></div>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"25 2","pages":"Pages 355-367"},"PeriodicalIF":8.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900177","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 : 2025-02-01DOI: 10.1016/j.ajt.2025.01.020
Krista L. Lentine , Jodi M. Smith , Grace R. Lyden , Jonathan M. Miller , Sarah E. Booker , Thomas G. Dolan , Kayla R. Temple , Samantha Weiss , Dzhuliyana Handarova , Ajay K. Israni , Jon J. Snyder
In 2023, the field of kidney transplantation faced both successes and challenges. A record 28,142 total kidney transplants were achieved in the United States, largely due to an increase in deceased donor kidney transplants (DDKTs). While the number of adult candidates listed for DDKT slightly increased, it remained below the level in 2019, with 11.4% of candidates waiting 5 years or more. Across racial and ethnic groups, Black adult candidates had the largest increase in DDKT rate in 2023, in parallel with the Organ Procurement and Transplantation Network policy to modify waiting time (implemented January 5, 2023). Following increases in death rates during the COVID-19 pandemic, pretransplant mortality declined in 2023 across various age, race and ethnicity, sex, and blood type categories, although mortality continued to vary substantially by donation service area. The rate of deceased donor kidneys that were recovered for transplant but not transplanted (nonuse) increased to a notable high of 27.9%, from 26.6% in 2022, with even higher rates for biopsied kidneys (41.4%), those from donors aged 65 years or older (72.2%), and kidneys with a kidney donor profile index of 85% or higher (72.5%). In contrast, nonuse of kidneys recovered from hepatitis C virus nucleic acid test–positive donors declined to 27.2% in 2023, from 43.0% in 2017, likely reflecting more common use of protocols incorporating direct-acting antiviral therapy. Disparities in access to living donor kidney transplant (LDKT) persist and particularly affect non-White and publicly insured patients. Delayed graft function has risen over the past decade, but appears to have plateaued, at 26.1% overall for adult recipients in 2023. Five-year graft survival rates were 90.0% for LDKT compared with 82.2% for DDKT in recipients aged 18-34 years, and 80.2% for LDKT versus 66.1% for DDKT in those aged 65 years or older.
{"title":"OPTN/SRTR 2023 Annual Data Report: Kidney","authors":"Krista L. Lentine , Jodi M. Smith , Grace R. Lyden , Jonathan M. Miller , Sarah E. Booker , Thomas G. Dolan , Kayla R. Temple , Samantha Weiss , Dzhuliyana Handarova , Ajay K. Israni , Jon J. Snyder","doi":"10.1016/j.ajt.2025.01.020","DOIUrl":"10.1016/j.ajt.2025.01.020","url":null,"abstract":"<div><div>In 2023, the field of kidney transplantation faced both successes and challenges. A record 28,142 total kidney transplants were achieved in the United States, largely due to an increase in deceased donor kidney transplants (DDKTs). While the number of adult candidates listed for DDKT slightly increased, it remained below the level in 2019, with 11.4% of candidates waiting 5 years or more. Across racial and ethnic groups, Black adult candidates had the largest increase in DDKT rate in 2023, in parallel with the Organ Procurement and Transplantation Network policy to modify waiting time (implemented January 5, 2023). Following increases in death rates during the COVID-19 pandemic, pretransplant mortality declined in 2023 across various age, race and ethnicity, sex, and blood type categories, although mortality continued to vary substantially by donation service area. The rate of deceased donor kidneys that were recovered for transplant but not transplanted (nonuse) increased to a notable high of 27.9%, from 26.6% in 2022, with even higher rates for biopsied kidneys (41.4%), those from donors aged 65 years or older (72.2%), and kidneys with a kidney donor profile index of 85% or higher (72.5%). In contrast, nonuse of kidneys recovered from hepatitis C virus nucleic acid test–positive donors declined to 27.2% in 2023, from 43.0% in 2017, likely reflecting more common use of protocols incorporating direct-acting antiviral therapy. Disparities in access to living donor kidney transplant (LDKT) persist and particularly affect non-White and publicly insured patients. Delayed graft function has risen over the past decade, but appears to have plateaued, at 26.1% overall for adult recipients in 2023. Five-year graft survival rates were 90.0% for LDKT compared with 82.2% for DDKT in recipients aged 18-34 years, and 80.2% for LDKT versus 66.1% for DDKT in those aged 65 years or older.</div></div>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"25 2","pages":"Pages S22-S137"},"PeriodicalIF":8.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143386741","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 : 2025-02-01DOI: 10.1016/j.ajt.2025.01.022
Allison J. Kwong , W. Ray Kim , John R. Lake , David P. Schladt , Dzhuliyana Handarova , Jesse Howell , Benjamin Schumacher , Samantha Weiss , Jon J. Snyder , Ajay K. Israni
The number of liver transplants performed in 2023 in the United States reached another record high, totaling 10,659 overall, of which 10,125 (95.0%) were in adult recipients and 534 (5.0%) were in pediatric recipients. This growth was driven by increased recovery of livers from older donors and donation after circulatory death (DCD) donors—likely related to the wider availability of machine perfusion technologies. The overall nonuse rate, or percent of livers recovered for transplant and not transplanted, was 9.7%, a decrease from the preceding years, and 16.7% of transplant recipients accepted DCD livers. There was also growth in living donation, representing 5.7% of adult transplants and 14.6% of pediatric transplants. In July 2023, the model for end-stage liver disease (MELD) 3.0 and pediatric end-stage liver disease (PELD)–creatinine scoring systems were updated from MELD-sodium and PELD, respectively, and criteria for status 1B qualification for pediatric candidates were updated. A major goal of MELD 3.0 was to address the sex disparity in deceased donor transplant rates. In 2023, the gap in deceased donor liver transplant rates between sexes narrowed, although the rate remained higher for adult male candidates compared with female candidates, and pretransplant mortality rates were higher among adult female candidates compared with male candidates. Alcohol-associated liver disease and metabolic dysfunction–associated steatohepatitis remained the leading indications for liver transplant.
{"title":"OPTN/SRTR 2023 Annual Data Report: Liver","authors":"Allison J. Kwong , W. Ray Kim , John R. Lake , David P. Schladt , Dzhuliyana Handarova , Jesse Howell , Benjamin Schumacher , Samantha Weiss , Jon J. Snyder , Ajay K. Israni","doi":"10.1016/j.ajt.2025.01.022","DOIUrl":"10.1016/j.ajt.2025.01.022","url":null,"abstract":"<div><div>The number of liver transplants performed in 2023 in the United States reached another record high, totaling 10,659 overall, of which 10,125 (95.0%) were in adult recipients and 534 (5.0%) were in pediatric recipients. This growth was driven by increased recovery of livers from older donors and donation after circulatory death (DCD) donors—likely related to the wider availability of machine perfusion technologies. The overall nonuse rate, or percent of livers recovered for transplant and not transplanted, was 9.7%, a decrease from the preceding years, and 16.7% of transplant recipients accepted DCD livers. There was also growth in living donation, representing 5.7% of adult transplants and 14.6% of pediatric transplants. In July 2023, the model for end-stage liver disease (MELD) 3.0 and pediatric end-stage liver disease (PELD)–creatinine scoring systems were updated from MELD-sodium and PELD, respectively, and criteria for status 1B qualification for pediatric candidates were updated. A major goal of MELD 3.0 was to address the sex disparity in deceased donor transplant rates. In 2023, the gap in deceased donor liver transplant rates between sexes narrowed, although the rate remained higher for adult male candidates compared with female candidates, and pretransplant mortality rates were higher among adult female candidates compared with male candidates. Alcohol-associated liver disease and metabolic dysfunction–associated steatohepatitis remained the leading indications for liver transplant.</div></div>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"25 2","pages":"Pages S193-S287"},"PeriodicalIF":8.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143386742","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 : 2025-02-01DOI: 10.1016/j.ajt.2025.01.024
Monica M. Colvin , Jodi M. Smith , Yoon Son Ahn , Kelsi A. Lindblad , Dzhuliyana Handarova , Ajay K. Israni , Jon J. Snyder
Despite unintended consequences and ongoing need for revision, the 2018 adult heart transplant policy revision continues to have a favorable impact as evidenced by increased transplant rates, decreased waitlist mortality, and more rapid transplant in higher acuity patients. In 2023, the total number of heart transplants in the United States increased 101.1% since 2012, reaching a record 4,599, of which 4,092 were performed in adults. Between 2022 and 2023 alone, 424 more adult heart transplants were performed, the largest annual increase this decade. Concurrently, the prevalence of heart donors after circulatory death increased to 14.0% in 2023. Candidates listed at adult statuses 1 and 2 underwent transplant more quickly (2,225.8 and 1,088.1 transplants per 100 patient-years, respectively). In 2023, adult waitlist mortality reached a low: 8.5 deaths per 100 patient-years. Multiorgan transplants (heart-liver and heart-kidney) in adults continue to increase, achieving comparable survival to that of heart transplant alone. Adults with congenital heart disease had the lowest pretransplant mortality of all diagnoses but also the lowest posttransplant survival, 76.1% at 5 years, emphasizing the need for consensus on best practices. In pediatric heart transplant, heart transplants increased 36.3% and new listings increased 34.0%, but the transplant rate decreased 14.9% resulting in increased waiting times. High-urgency listings increased, with 83.6% of heart transplants performed for status 1A. Pediatric waitlist mortality has declined 53.4% since 2012, but remains substantial: 11.7 deaths per 100 patient-years. In 2023, 5-year posttransplant survival was 80.3% in adult recipients and 84.4% in pediatric recipients.
{"title":"OPTN/SRTR 2023 Annual Data Report: Heart","authors":"Monica M. Colvin , Jodi M. Smith , Yoon Son Ahn , Kelsi A. Lindblad , Dzhuliyana Handarova , Ajay K. Israni , Jon J. Snyder","doi":"10.1016/j.ajt.2025.01.024","DOIUrl":"10.1016/j.ajt.2025.01.024","url":null,"abstract":"<div><div>Despite unintended consequences and ongoing need for revision, the 2018 adult heart transplant policy revision continues to have a favorable impact as evidenced by increased transplant rates, decreased waitlist mortality, and more rapid transplant in higher acuity patients. In 2023, the total number of heart transplants in the United States increased 101.1% since 2012, reaching a record 4,599, of which 4,092 were performed in adults. Between 2022 and 2023 alone, 424 more adult heart transplants were performed, the largest annual increase this decade. Concurrently, the prevalence of heart donors after circulatory death increased to 14.0% in 2023. Candidates listed at adult statuses 1 and 2 underwent transplant more quickly (2,225.8 and 1,088.1 transplants per 100 patient-years, respectively). In 2023, adult waitlist mortality reached a low: 8.5 deaths per 100 patient-years. Multiorgan transplants (heart-liver and heart-kidney) in adults continue to increase, achieving comparable survival to that of heart transplant alone. Adults with congenital heart disease had the lowest pretransplant mortality of all diagnoses but also the lowest posttransplant survival, 76.1% at 5 years, emphasizing the need for consensus on best practices. In pediatric heart transplant, heart transplants increased 36.3% and new listings increased 34.0%, but the transplant rate decreased 14.9% resulting in increased waiting times. High-urgency listings increased, with 83.6% of heart transplants performed for status 1A. Pediatric waitlist mortality has declined 53.4% since 2012, but remains substantial: 11.7 deaths per 100 patient-years. In 2023, 5-year posttransplant survival was 80.3% in adult recipients and 84.4% in pediatric recipients.</div></div>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"25 2","pages":"Pages S329-S421"},"PeriodicalIF":8.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143386751","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 : 2025-02-01DOI: 10.1016/j.ajt.2024.08.021
Sameer Patel , Clemens Gutmann , Robert Loveridge , Tasneem Pirani , Chris Willars , Andre Vercueil , Milena Angelova-Chee , Varuna Aluvihare , Michael Heneghan , Krishna Menon , Nigel Heaton , William Bernal , Mark McPhail , Elton Gelandt , Lisa Morgan , Michael Whitehorne , Julia Wendon , Georg Auzinger
Data on perioperative extracorporeal membrane oxygenation (ECMO) in liver transplantation (LT) are scarce. ECMO has been used preoperatively, intraoperatively, and postoperatively for a variety of indications at our center. This retrospective, single-center study of ECMO use peri-LT aimed to describe predictors for successful outcome in this highly select cohort of patients. Demographics, support method, and indication for LT were compared between survivors and nonsurvivors. Twenty-nine patients received venovenous (V-V; n = 20), venoarterial (V-A; n = 8), and venoarteriovenous (n = 1) ECMO. Twelve (41.4%) patients were bridged to emergency LT for acute liver failure, and emergency redo LT. Four (13.3%) patients required intraoperative V-A ECMO salvage, 2 necessitating extracorporeal cardiopulmonary resuscitation. Thirteen (43.3%) patients required ECMO support after LT: V-V ECMO (n = 9); V-A ECMO (n = 1); and extracorporeal cardiopulmonary resuscitation (n = 3) between postoperative days 2 to 30. Overall, 19 patients (65.5%) were successfully weaned off ECMO; 15 (51.7%) survived to intensive care unit discharge. All patients who underwent intraoperative salvage ECMO and all who were bridged to emergency redo LT died. Peri-LT ECMO is feasible. Post-LT ECMO outcomes are encouraging, in particular for V-V ECMO. Intraoperative ECMO salvage, uncontrolled sepsis, and graft failure are associated with poor outcomes.
{"title":"Perioperative extracorporeal membrane oxygenation in liver transplantation—bridge to transplantation, intraoperative salvage, and postoperative support: outcomes and predictors for survival in a large-volume liver transplant center","authors":"Sameer Patel , Clemens Gutmann , Robert Loveridge , Tasneem Pirani , Chris Willars , Andre Vercueil , Milena Angelova-Chee , Varuna Aluvihare , Michael Heneghan , Krishna Menon , Nigel Heaton , William Bernal , Mark McPhail , Elton Gelandt , Lisa Morgan , Michael Whitehorne , Julia Wendon , Georg Auzinger","doi":"10.1016/j.ajt.2024.08.021","DOIUrl":"10.1016/j.ajt.2024.08.021","url":null,"abstract":"<div><div>Data on perioperative extracorporeal membrane oxygenation (ECMO) in liver transplantation (LT) are scarce. ECMO has been used preoperatively, intraoperatively, and postoperatively for a variety of indications at our center. This retrospective, single-center study of ECMO use peri-LT aimed to describe predictors for successful outcome in this highly select cohort of patients. Demographics, support method, and indication for LT were compared between survivors and nonsurvivors. Twenty-nine patients received venovenous (V-V; <em>n</em> = 20), venoarterial (V-A; <em>n</em> = 8), and venoarteriovenous (<em>n</em> = 1) ECMO. Twelve (41.4%) patients were bridged to emergency LT for acute liver failure, and emergency redo LT. Four (13.3%) patients required intraoperative V-A ECMO salvage, 2 necessitating extracorporeal cardiopulmonary resuscitation. Thirteen (43.3%) patients required ECMO support after LT: V-V ECMO (n = 9); V-A ECMO (n = 1); and extracorporeal cardiopulmonary resuscitation (<em>n</em> = 3) between postoperative days 2 to 30. Overall, 19 patients (65.5%) were successfully weaned off ECMO; 15 (51.7%) survived to intensive care unit discharge. All patients who underwent intraoperative salvage ECMO and all who were bridged to emergency redo LT died. Peri-LT ECMO is feasible. Post-LT ECMO outcomes are encouraging, in particular for V-V ECMO. Intraoperative ECMO salvage, uncontrolled sepsis, and graft failure are associated with poor outcomes.</div></div>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"25 2","pages":"Pages 396-405"},"PeriodicalIF":8.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054266","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 : 2025-02-01DOI: 10.1016/j.ajt.2024.09.008
Miguel Nunez , Ali Abbasi , Marilyn McEnhill , Jessica Brennan , Taryn Shappell , Sarah Kinnier , Erica Winnicki , Peter Stock
This study aimed to investigate the effects of documentation status on pediatric kidney transplant outcomes in a single-center setting, emphasizing the significance of state insurance access for undocumented patients and federal policies like Deferred Action for Childhood Arrivals (DACA) on patient outcomes. A cohort of 283 patients, including 48 undocumented individuals, who received their first kidney transplant as children between 1998 and 2011 was analyzed. There was no significant difference in unadjusted all-cause (P = .91) and death-censored (P = .38) graft survival between undocumented patients and patients with permanent legal status, subsequently referred to as US residents. Additionally, in the Cox proportional hazards model, immigration status was not significantly associated with all-cause graft survival (hazard ratio 0.87, 95% CI 0.51-1.46, P = .6). Telephone interviews were conducted with the undocumented cohort. Forty-one of 48 of the undocumented recipients were contacted. Ninety-five percent had access to insurance with 68.3% on Medicaid or Medicare. DACA recipients exhibited higher employment rates (88% vs 67%, P = .11) and were more likely to complete a degree beyond high school (47.1% vs 12.5%, P = .01). Immigration status did not impact long-term graft survival, suggesting eligibility expansions for state-funded insurance and DACA may improve access to transplant care for undocumented patients. Moreover, DACA recipients showed trends toward increased employment and education compared to non-DACA recipients.
{"title":"Long-term impact of immigration status on outcomes in pediatric kidney transplant recipients","authors":"Miguel Nunez , Ali Abbasi , Marilyn McEnhill , Jessica Brennan , Taryn Shappell , Sarah Kinnier , Erica Winnicki , Peter Stock","doi":"10.1016/j.ajt.2024.09.008","DOIUrl":"10.1016/j.ajt.2024.09.008","url":null,"abstract":"<div><div>This study aimed to investigate the effects of documentation status on pediatric kidney transplant outcomes in a single-center setting, emphasizing the significance of state insurance access for undocumented patients and federal policies like Deferred Action for Childhood Arrivals (DACA) on patient outcomes. A cohort of 283 patients, including 48 undocumented individuals, who received their first kidney transplant as children between 1998 and 2011 was analyzed. There was no significant difference in unadjusted all-cause (<em>P</em> = .91) and death-censored (<em>P</em> = .38) graft survival between undocumented patients and patients with permanent legal status, subsequently referred to as US residents. Additionally, in the Cox proportional hazards model, immigration status was not significantly associated with all-cause graft survival (hazard ratio 0.87, 95% CI 0.51-1.46, <em>P</em> = .6). Telephone interviews were conducted with the undocumented cohort. Forty-one of 48 of the undocumented recipients were contacted. Ninety-five percent had access to insurance with 68.3% on Medicaid or Medicare. DACA recipients exhibited higher employment rates (88% vs 67%, <em>P</em> = .11) and were more likely to complete a degree beyond high school (47.1% vs 12.5%, <em>P</em> = .01). Immigration status did not impact long-term graft survival, suggesting eligibility expansions for state-funded insurance and DACA may improve access to transplant care for undocumented patients. Moreover, DACA recipients showed trends toward increased employment and education compared to non-DACA recipients.</div></div>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"25 2","pages":"Pages 368-375"},"PeriodicalIF":8.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277483","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 : 2025-02-01DOI: 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":"10.1016/j.ajt.2024.09.022","url":null,"abstract":"","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"25 2","pages":"Pages 234-236"},"PeriodicalIF":8.9,"publicationDate":"2025-02-01","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}
Natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) is a major mechanism of humoral allograft injury. FCGR3A V176/F176 polymorphism influences ADCC activity. Additionally, NK cell FcγRIIc expression, dictated by the Q13/STP13 polymorphism, was never investigated in kidney transplantation. To assess the clinical relevance of FCGR2C Q13/STP13 polymorphism in conjunction with FCGR3A V176/F176 polymorphism, 242 kidney transplant recipients were genotyped. NK cell Fc gamma receptor (FcγR) expression and ADCC activity were assessed. RNA sequencing was performed on kidney allograft biopsies to explore the presence of infiltrating FcγR+ NK cells. The FCGR2C Q13 allele was enriched in antibody-mediated rejection patients. FcγRIIc Q13+ NK cells had higher ADCC activity than FcγRIIc Q13– NK cells. In combination with the high-affinity FCGR3A V176 allele, Q13+V176+ NK cells were the most functionally potent. Q13+ was associated with worse microvascular inflammation and a higher risk of allograft loss. Among V176– patients, previously described in the literature as lower-risk patients, Q13+V176– showed a lower graft survival than Q13–V176– patients. In antibody-mediated rejection biopsies, FCGR2C transcripts were enriched and associated with ADCC-related transcripts. Our results suggest that FCGR2C Q13 in addition to FCGR3A V176 is a significant risk allele that may enhance NK cell-mediated ADCC and contribute to allograft injury and poor survival.
NK 细胞介导的抗体依赖性细胞毒性（ADCC）是体液同种异体移植损伤的主要机制。FCGR3A V176/F176 多态性会影响 ADCC 活性。此外，由 Q13/STP13 多态性决定的 NK 细胞 FcγRIIc 表达在肾移植中从未被研究过。为了评估FCGR2C Q13/STP13多态性与FCGR3A V176/F176多态性的临床相关性，对242名肾移植受者进行了基因分型。对 NK 细胞 FcγR 表达和 ADCC 活性进行了评估。对肾移植活组织进行了 RNA 测序，以探究是否存在浸润的 FcγR+ NK 细胞。FCGR2C Q13等位基因在抗体介导的排斥反应（ABMR）患者中富集。FcγRIIc Q13+ NK细胞的ADCC活性高于FcγRIIc Q13- NK细胞。与高亲和力的 FCGR3A V176 等位基因结合，Q13+V176+ NK 细胞的功能最强。Q13+与更严重的微血管炎症和更高的异体移植损失风险有关。在以前文献中被描述为低风险患者的 V176- 患者中，Q13+V176- 患者的移植物存活率低于 Q13-V176- 患者。在ABMR活检中，FCGR2C转录本富集并与ADCC相关转录本相关。我们的研究结果表明，除FCGR3A V176外，FCGR2C Q13也是一个重要的风险等位基因，它可能会增强NK细胞介导的ADCC，导致异体移植物损伤和存活率低下。
{"title":"FCGR2C Q13 and FCGR3A V176 alleles jointly associate with worse natural killer cell-mediated antibody-dependent cellular cytotoxicity and microvascular inflammation in kidney allograft antibody-mediated rejection","authors":"Elodie Bailly , Camila Macedo , Xinyan Gu , Deborah Hollingshead , Carol Bentlejewski , Erica Fong , Penelope A. Morel , Parmjeet Randhawa , Adriana Zeevi , Carmen Lefaucheur , Diana Metes","doi":"10.1016/j.ajt.2024.09.018","DOIUrl":"10.1016/j.ajt.2024.09.018","url":null,"abstract":"<div><div>Natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) is a major mechanism of humoral allograft injury. <em>FCGR3A</em> V<sup>176</sup>/F<sup>176</sup> polymorphism influences ADCC activity. Additionally, NK cell FcγRIIc expression, dictated by the Q<sup>13</sup>/STP<sup>13</sup> polymorphism, was never investigated in kidney transplantation. To assess the clinical relevance of <em>FCGR2C</em> Q<sup>13</sup>/STP<sup>13</sup> polymorphism in conjunction with <em>FCGR3A</em> V<sup>176</sup>/F<sup>176</sup> polymorphism, 242 kidney transplant recipients were genotyped. NK cell Fc gamma receptor (FcγR) expression and ADCC activity were assessed. RNA sequencing was performed on kidney allograft biopsies to explore the presence of infiltrating FcγR+ NK cells. The <em>FCGR2C</em> Q<sup>13</sup> allele was enriched in antibody-mediated rejection patients. FcγRIIc Q<sup>13</sup>+ NK cells had higher ADCC activity than FcγRIIc Q<sup>13</sup>– NK cells. In combination with the high-affinity <em>FCGR3A</em> V<sup>176</sup> allele, Q<sup>13</sup>+V<sup>176</sup>+ NK cells were the most functionally potent. Q<sup>13</sup>+ was associated with worse microvascular inflammation and a higher risk of allograft loss. Among V<sup>176</sup>– patients, previously described in the literature as lower-risk patients, Q<sup>13</sup>+V<sup>176</sup>– showed a lower graft survival than Q<sup>13</sup>–V<sup>176</sup>– patients. In antibody-mediated rejection biopsies, <em>FCGR2C</em> transcripts were enriched and associated with ADCC-related transcripts. Our results suggest that <em>FCGR2C</em> Q<sup>13</sup> in addition to <em>FCGR3A</em> V<sup>176</sup> is a significant risk allele that may enhance NK cell-mediated ADCC and contribute to allograft injury and poor survival.</div></div>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"25 2","pages":"Pages 302-315"},"PeriodicalIF":8.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142329263","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 : 2025-02-01DOI: 10.1016/j.ajt.2024.09.028
Daniel J. Ahn , Allison J. Kwong , Anji E. Wall , William F. Parker
In the US liver allocation system, nonstandardized model for end-stage liver disease (MELD) exceptions (NSEs) increase the waitlist priority of candidates whose MELD scores are felt to underestimate their true medical urgency. We determined whether NSEs accurately depict pretransplant mortality risk by performing mixed-effects Cox proportional hazards models and estimating concordance indices. We also studied the change in frequency of NSEs after the National Liver Review Board’s implementation in May 2019. Between June 2016 and April 2022, 60,322 adult candidates were listed, of whom 10,280 (17.0%) received an NSE at least once. The mean allocation MELD was 23.9, an increase of 12.0 points from the mean laboratory MELD of 11.9 (P < .001). A 1-point increase in allocation MELD score due to an NSE was associated with, on average, a 2% reduction in hazard of pretransplant death (cause-specific hazard ratio: 0.98; 95% CI: 0.96, 1.00; P = .02) compared with those with the same laboratory MELD. Laboratory MELD was more accurate than allocation MELD with NSEs in rank-ordering candidates (c-index: 0.889 vs 0.857). The proportion of candidates with NSEs decreased significantly after the National Liver Review Board from 21.5% to 12.8% (P < .001). NSEs substantially increase the waitlist priority of candidates with objectively low medical urgency.
{"title":"Association of nonstandardized model for end-stage liver disease score exceptions with waitlist mortality in adult liver transplant candidates","authors":"Daniel J. Ahn , Allison J. Kwong , Anji E. Wall , William F. Parker","doi":"10.1016/j.ajt.2024.09.028","DOIUrl":"10.1016/j.ajt.2024.09.028","url":null,"abstract":"<div><div>In the US liver allocation system, nonstandardized model for end-stage liver disease (MELD) exceptions (NSEs) increase the waitlist priority of candidates whose MELD scores are felt to underestimate their true medical urgency. We determined whether NSEs accurately depict pretransplant mortality risk by performing mixed-effects Cox proportional hazards models and estimating concordance indices. We also studied the change in frequency of NSEs after the National Liver Review Board’s implementation in May 2019. Between June 2016 and April 2022, 60,322 adult candidates were listed, of whom 10,280 (17.0%) received an NSE at least once. The mean allocation MELD was 23.9, an increase of 12.0 points from the mean laboratory MELD of 11.9 (<em>P</em> < .001). A 1-point increase in allocation MELD score due to an NSE was associated with, on average, a 2% reduction in hazard of pretransplant death (cause-specific hazard ratio: 0.98; 95% CI: 0.96, 1.00; <em>P</em> = .02) compared with those with the same laboratory MELD. Laboratory MELD was more accurate than allocation MELD with NSEs in rank-ordering candidates (c-index: 0.889 vs 0.857). The proportion of candidates with NSEs decreased significantly after the National Liver Review Board from 21.5% to 12.8% (<em>P</em> < .001). NSEs substantially increase the waitlist priority of candidates with objectively low medical urgency.</div></div>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"25 2","pages":"Pages 385-395"},"PeriodicalIF":8.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337684","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 : 2025-02-01DOI: 10.1016/j.ajt.2024.09.032
Audrey E. Brown , Yvonne M. Kelly , Arya Zarinsefat , Raphael P.H. Meier , Giulia Worner , Mehdi Tavakol , Minnie M. Sarwal , Zoltan G. Laszik , Peter G. Stock , Tara K. Sigdel
Pancreas transplantation improves glycemic control and mortality in patients with diabetes but requires aggressive immunosuppression to control the alloimmune and autoimmune response. Recent developments in “omics” methods have provided gene transcript-based biomarkers for organ transplant rejection. The tissue Common Response Module (tCRM) score is developed to identify the severity of rejection in kidney, heart, liver, and lung transplants. Still, it has not yet been validated in pancreas transplants (PT). We evaluated the tCRM score’s relevance in PT and additional markers of acute cellular rejection (ACR) for PT. An analysis of 51 pancreas biopsies with ACR identified 37 genes and 56 genes significantly upregulated in the case of grade 3 and grade 2 ACR, respectively (P < .05). Significant differences were seen with higher grades of rejection among several transcripts. Of the 22 genes differentially expressed in grade 3 ACR, 18 were also differentially expressed in grade 2 ACR. The rejection signal was attributable to activated leukocytes’ infiltration. Significantly higher tCRM scores were found in grade 3 ACR (P = .007) and grade 2 ACR (P = .004), compared to normal samples. The tCRM score was able to distinguish treatment-resistant cases from those successfully treated for rejection.
{"title":"Gene expression–based molecular scoring of pancreas transplant rejection for a quantitative assessment of rejection severity and resistance to treatment","authors":"Audrey E. Brown , Yvonne M. Kelly , Arya Zarinsefat , Raphael P.H. Meier , Giulia Worner , Mehdi Tavakol , Minnie M. Sarwal , Zoltan G. Laszik , Peter G. Stock , Tara K. Sigdel","doi":"10.1016/j.ajt.2024.09.032","DOIUrl":"10.1016/j.ajt.2024.09.032","url":null,"abstract":"<div><div>Pancreas transplantation improves glycemic control and mortality in patients with diabetes but requires aggressive immunosuppression to control the alloimmune and autoimmune response. Recent developments in “omics” methods have provided gene transcript-based biomarkers for organ transplant rejection. The tissue Common Response Module (tCRM) score is developed to identify the severity of rejection in kidney, heart, liver, and lung transplants. Still, it has not yet been validated in pancreas transplants (PT). We evaluated the tCRM score’s relevance in PT and additional markers of acute cellular rejection (ACR) for PT. An analysis of 51 pancreas biopsies with ACR identified 37 genes and 56 genes significantly upregulated in the case of grade 3 and grade 2 ACR, respectively (<em>P</em> < .05). Significant differences were seen with higher grades of rejection among several transcripts. Of the 22 genes differentially expressed in grade 3 ACR, 18 were also differentially expressed in grade 2 ACR. The rejection signal was attributable to activated leukocytes’ infiltration. Significantly higher tCRM scores were found in grade 3 ACR (<em>P</em> = .007) and grade 2 ACR (<em>P</em> = .004), compared to normal samples. The tCRM score was able to distinguish treatment-resistant cases from those successfully treated for rejection.</div></div>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"25 2","pages":"Pages 316-328"},"PeriodicalIF":8.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337685","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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