Donation After Brain Death Donors Research Articles

Promising Results of Kidney Transplantation From Donors Following Euthanasia During 10-Year Follow-Up: A Nationwide Cohort Study.

The outcome of kidneys transplanted following organ donation after euthanasia (ODE) remains unclear. This study analyzed all kidney transplantations in the Netherlands from January 2012 to December 2021, comparing the outcomes following ODE, donation after circulatory death (DCD-III), and donation after brain death (DBD). 9,208 kidney transplantations were performed: 148 ODE, 2118 DCD-III, and 1845 DBD. Initial graft function was compared between these categories. Immediate graft function, delayed graft function and primary non-function in ODE kidney recipients were 76%, 22%, and 2%, respectively, 47%, 50% and 3% in DCD-III kidney recipients and 73%, 25%, and 2% in DBD kidney recipients (overall p-value: p < 0.001). The number of kidneys transplanted over a median follow-up period of 4.0 years (IQR 2.0-6.6), was 1810, including 72 ODE, 958 DCD-III and 780 DBD kidneys. In this period, 213 grafts (11.8%) failed [7 grafts (9.7%) from ODE donors, 93 grafts (9.7%) from DCD-III donors, and 113 grafts (14.5%) from DBD donors]. Kidneys transplanted after euthanasia have a good immediate graft function, a comparable longitudinal 10years eGFR, and similar graft failure hazard to kidneys from DCD-III and DBD. Kidney transplantation following ODE is a valuable and safe contribution to the donor pool.

Routine end-ischemic hypothermic machine perfusion in liver transplantation from donors after brain death: results of two-year follow-up of a randomized controlled trial.

Data on routine hypothermic machine perfusion of livers procured from donors after brain death (DBD) are scarce, and the benefits of the method have only been demonstrated in extended criteria grafts. The aim of this study was to assess if end-ischemic dual hypothermic oxygenated machine perfusion (dHOPE) is superior to static cold storage (SCS) in preservation of livers procured from DBD donors with respect to long-term outcomes. Existing data on short-term outcomes favours dHOPE in patients receiving high-risk grafts. This prospective randomized controlled trial included 104 recipients of DBD livers randomly assigned to static cold storage arm (78 patients) and dHOPE arm (26 patients). Endpoints of interest were occurrence of biliary complications (biliary fistula, anastomotic, and nonanastomotic strictures) and overall patient (OS) and graft survival (GS) during two-year follow-up. A total of 36 patients developed biliary complications (at least one event) - 6 events in dHOPE arm and 30 in SCS arm. There was no significant difference in biliary complications between groups (23.7% vs. 43.4% [P=0.11]). No differences were found significant with respect to anastomotic (19.9% vs. 33.7% [P=0.20]) and non-anastomotic strictures (0% vs. 11.1% [P=0.10]) as well as biliary fistulas (11.7% vs. 12.2% [P=0.93]). Survival analysis did not show significantly different result in the study population - OS: 92.3% in dHOPE and 83.9% in SCS (P=0.35), and GS: 92.3% and 81.4% (P=0.23), respectively. However, significant difference in GS was noted in recipients of high-risk grafts - 100% in dHOPE and 73.1% in SCS, respectively (P=0.038). The long-term outcome data suggest that the routine use of dHOPE may be beneficial for recipients of high-risk grafts from DBD donors. The present study does not provide any evidence for benefits of dHOPE in low-risk grafts.

Ex Situ Left Ventricular Pressure-Volume Loop Analyses for Donor Hearts: Proof of Concept in an Ovine Experimental Model.

Ex situ heart perfusion (ESHP) has emerged as an important strategy to preserve donation after brain death (DBD) and donation after circulatory death (DCD) donor hearts. Clinically, both DBD and DCD hearts are successfully preserved using ESHP. Viability assessment is currently based on biochemical values, while a reliable method for graft function assessment in a physiologic working mode is unavailable. As functional assessment during ESHP has demonstrated the highest predictive value of outcome post-transplantation, this is an important area for improvement. In this study, a novel method for ex situ assessment of left ventricular function with pressure-volume loop analyses is evaluated. Ovine hearts were functionally evaluated during normothermic ESHP with the novel pressure-volume loop system. This system provides an afterload and adjustable preload to the left ventricle. By increasing the preload and measuring end-systolic elastance, the system could successfully assess the left ventricular function. End-systolic elastance at 60min and 120min was 2.8 ± 1.8mmHg/mL and 2.7 ± 0.7mmHg/mL, respectively. In this study we show a novel method for functional graft assessment with ex situ pressure-loop analyses during ESHP. When further validated, this method for pressure-volume assessments, could be used for better graft selection in both DBD and DCD donor hearts.

Should advanced donor age be a deterrent in the utilization of grafts from donation after cardiac death in deceased donor liver transplantation? The Toronto experience.

Advanced donor age paired with donation after cardiac death (DCD) increases the risk of transplantation, precluding widespread use of grafts from such donors worldwide. Our aim was to analyze outcomes of liver transplantation using grafts from older DCD donors and donation after brain death (DBD) donors. Patients who underwent liver transplantation using grafts from deceased donors between January 2016 and December 2021 were included in the study. Short-and long-term outcomes were analyzed for 4 groups of patients: those who received DCD and DBD grafts from younger (< 50 yr) and older (≥ 50 yr) donors. Of the 807 patients included in the analysis, 44.7% (n = 361) of grafts were received from older donors, with grafts for older DCD donors comprising 4.7% of the total cohort (n = 38). Patients who received grafts from older donors had a lower incidence of biliary strictures than those who received grafts from younger donors (7.9% v. 20.0% for DCD donation, p = 0.14, and 4.9% v. 6.8% for DBD donation, p = 0.34), with a significantly lower incidence of ischemic-type biliary strictures in patients who received grafts from older versus younger DCD donors (2.6% v. 18.0%, p = 0.04). There was no difference in 1- and 3-year graft survival rates among patients who received grafts from older and younger DCD donors (92.1% v. 90.8% and 80.2% v. 80.9%, respectively) and those who received grafts from older and younger DBD donors (90.1% v. 93.2% and 85.3% v. 84.4%, respectively) (p = 0.85). Pretransplantation admission to the intensive care unit (hazard ratio [HR] 9.041, p < 0.001) and nonalcoholic steatohepatitis (HR 2.197, p = 0.02) were found to significantly affect survival of grafts from older donors. Donor age alone should not be the criterion to determine the acceptability of grafts in liver transplantation. With careful selection criteria, older DCD donors could make a valuable contribution to expanding the liver donor pool, with grafts that produce comparable results to those obtained with standard-criteria grafts.

Outcomes of Heart Transplant Donation After Circulatory Death

BackgroundHeart transplantation using donation after circulatory death (DCD) allografts is increasingly common, expanding the donor pool and reducing transplant wait times. However, data remain limited on clinical outcomes. ObjectivesWe sought to compare 6-month and 1-year clinical outcomes between recipients of DCD hearts, most of them recovered with the use of normothermic regional perfusion (NRP), and recipients of donation after brain death (DBD) hearts. MethodsWe conducted a single-center retrospective observational study of all adult heart-only transplants from January 2020 to January 2023. Recipient and donor data were abstracted from medical records and the United Network for Organ Sharing registry, respectively. Survival analysis and Cox regression were used to compare the groups. ResultsDuring the study period, 385 adults (median age 57.4 years [IQR: 48.0-63.7 years]) underwent heart-only transplantation, including 122 (32%) from DCD donors, 83% of which were recovered with the use of NRP. DCD donors were younger and had fewer comorbidities than DBD donors. DCD recipients were less often hospitalized before transplantation and less likely to require pretransplantation temporary mechanical circulatory support compared with DBD recipients. There were no significant differences between groups in 1-year survival, incidence of severe primary graft dysfunction, treated rejection during the first year, or likelihood of cardiac allograft vasculopathy at 1 year after transplantation. ConclusionsIn the largest single-center comparison of DCD and DBD heart transplantations to date, outcomes among DCD recipients are noninferior to those of DBD recipients. This study adds to the published data supporting DCD donors as a safe means to expand the heart donor pool.

Transplant Outcomes After Exposure of Deceased Kidney Donors to Contrast Medium.

The administration of contrast medium is associated with acute kidney injury; however, the effect of exposure of a deceased organ donor to contrast medium on kidney transplant outcomes has been poorly studied. A retrospective analysis of all deceased kidney donors between 2011 and 2021 and their corresponding recipients in the Netherlands was conducted. Multivariable analyses were performed to assess the associations between contrast medium exposure and delayed graft function (DGF)/graft survival. Linear mixed models were used to assess the differences in mean estimated glomerular filtration rate values in recipients 1 to 6 y after transplantation. In total, 2177 donors and 3638 corresponding kidney graft recipients were included. Twenty-four percent of the donors (n = 520) were exposed to contrast medium, corresponding to 23% of recipients (n = 832). DGF was observed in 36% (n = 1321) and primary nonfunction in 3% (n = 122) of recipients. DGF rates for donation after brain death (DBD) and donation after circulatory death (DCD) donors showed no significant effect of contrast medium exposure (P = 0.15 and P = 0.60 for DBD and DCD donors, respectively). In multivariable analyses, contrast medium administration was not significantly associated with a higher DGF risk (odds ratio 1.06; 95% confidence interval, 0.86-1.36; P = 0.63) nor was a significant predictor for death-censored graft failure (hazard ratio 1.01; 95% confidence interval, 0.77-1.33; P = 0.93). Linear mixed models showed no difference in mean estimated glomerular filtration rate values in recipients 1 to 6 y posttransplantation (P = 0.78). This study indicates that contrast medium administration in DBD and DCD donors has no negative effect on early and long-term kidney graft function.

Donation after circulatory death improves probability of heart transplantation in waitlisted candidates and results in post-transplant outcomes similar to those achieved with brain-dead donors

ObjectiveTo quantitate the impact of heart donation after circulatory death (DCD) donor utilization on both waitlist and post-transplant outcomes in the United States. MethodsThe United Network for Organ Sharing database was queried to identify all adult waitlisted and transplanted candidates between October 18, 2018, and December 31, 2022. Waitlisted candidates were stratified according to whether they had been approved for donation after brain death (DBD) offers only or also approved for DCD offers. The cumulative incidence of transplantation was compared between the 2 cohorts. In a post-transplant analysis, 1-year post-transplant survival was compared between unmatched and propensity-score-matched cohorts of DBD and DCD recipients. ResultsA total of 14,803 candidates were waitlisted, including 12,287 approved for DBD donors only and 2516 approved for DCD donors. Overall, DCD approval was associated with an increased sub-hazard ratio (HR) for transplantation and a lower sub-HR for delisting owing to death/deterioration after risk adjustment. In a subgroup analysis, candidates with blood type B and status 4 designation received the greatest benefit from DCD approval. A total of 12,238 recipients underwent transplantation, 11,636 with DBD hearts and 602 with DCD hearts. Median waitlist times were significantly shorter for status 3 and status 4 recipients receiving DCD hearts. One-year post-transplant survival was comparable between unmatched and propensity score–matched cohorts of DBD and DCD recipients. ConclusionsThe use of DCD hearts confers a higher probability of transplantation and a lower incidence of death/deterioration while on the waitlist, particularly among certain subpopulations such as status 4 candidates. Importantly, the use of DCD donors results in similar post-transplant survival as DBD donors.

SP5.10 Is there a difference in Survival Outcomes of Dual Kidney Transplants (DKTs) of Allografts Procured from DCD versus DBD Donors in absence of a Dedicated National Pathology Service? A Propensity Score Analysis of UK Transplant Registry. An Epidemiology in Transplant Study Group (ETrSG) Initiative

Abstract Background Dual kidney transplants (DKTs) are generally from supra-marginal or small-for-size kidneys that are implanted to provide optimum total nephron-mass. Glomerulosclerosis Pathology Scoring is used globally to guide whether single or DKT are indicated for transplant. Additionally, there are reported concerns regarding donation after cardiac death (DCD) transplant outcomes’ inferiority to donation after brain death (DBD) transplants but there are no reported survival outcomes of DKT procured from DCD v/s DBD donors. Aim This study aims to research if there is a difference in survival outcomes of DKTs of allografts procured from DCD versus DBD Donors in the UK. Methods In this exploratory analysis, adults who underwent DKT in the UK between Jan 1, 2000, and December 31, 2019, were identified in the NHSBT-Transplant registry data. Post-transplantation graft survival at 1&amp; 3 years was assessed with cox-regression analysis, with propensity scores being used to control for selection bias. Results 51,961 renal transplants were reported to NHSBT during the study period, of whom 525 were DKT. After confounders were controlled for with propensity scores, no significant differences in survival outcomes were found between DCD and DBD transplants. Region of Transplant (OR 1.6, 1.0-2.5; p=0.02), transplant post-Year-2011 (OR 3.0, 1.7-5.2; p&amp;lt;0.00), and non-diabetic donors (OR 2.1, 1.1-3.9, p=0.009) were associated with better graft survival, while DBD transplants were associated with low delayed graft function rates (OR 0.4, 0.27 - 0.59; p&amp;lt;.001). Conclusions Survival outcomes of DKT procured from DCD versus DBD donors are equivalent. These results are admirable as the UK does not have a dedicated National-Pathology-Service to report pre-transplant renal biopsies.

Decreased Utilization Rate of Grafts for Liver Transplantation After Implementation of Acuity Circle-based Allocation.

The allocation system for livers began using acuity circles (AC) in 2020. In this study, we sought to evaluate the impact of AC policy on the utilization rate for liver transplantation (LT). Using the US national registry data between 2018 and 2022, LTs were equally divided into 2 eras: pre-AC (before February 4, 2020) and post-AC (February 4, 2020, and after). Deceased potential liver donors were defined as deceased donors from whom at least 1 organ was procured. The annual number of deceased potential liver donors increased post-AC (from 10 423 to 12 259), approaching equal to that of new waitlist registrations for LT (n = 12 801). Although the discard risk index of liver grafts was comparable between the pre- and post-AC eras, liver utilization rates in donation after brain death (DBD) and donation after circulatory death (DCD) donors were lower post-AC ( P < 0.01; 79.8% versus 83.4% and 23.7% versus 26.0%, respectively). Recipient factors, ie, no recipient located, recipient determined unsuitable, or time constraints, were more likely to be reasons for nonutilization after implementation of the AC allocation system compared to the pre-AC era (20.0% versus 12.3% for DBD donors and 50.1% versus 40.8% for DCD donors). Among non-high-volume centers, centers with lower utilization of marginal DBD donors or DCD donors were more likely to decrease LT volume post-AC. Although the number of deceased potential liver donors has increased, overall liver utilization among deceased donors has decreased in the post-AC era. To maximize the donor pool for LT, future efforts should target specific reasons for liver nonutilization.

Impact of Portable Normothermic Machine Perfusion for Liver Transplantation From Adult Deceased Donors.

To assess how liver allografts preserved using portable normothermic machine perfusion (NMP) compare against those that underwent ischemic cold storage (ICS) in the setting of donation after brain death (DBD) and donation after circulatory death (DCD) liver transplantation (LT). Compared with conventional ICS, NMP may offer more homeostatic preservation, permit physiological assessment of organ function, and provide opportunities for graft improvement/modification. We report a single-center US experience of liver NMP. A single-center, retrospective analysis of collected data on 541 adult whole LTs from 469 DBD donors [NMP (n = 58) vs ICS (n = 411)] and 72 DCD donors [NMP (n = 52) vs ICS (n = 20)] between January 2016 and December 2022. In DBD LT, male sex [odds ratio (95% CI): 1.83 (1.08-3.09)] and >10% macrosteatosis of the donor liver [1.85 (1.10-3.10)] were statistically significant independent risk factors of early allograft dysfunction (EAD). Donor age >40 years and cold ischemia time >7 hours were independent risk factors of reperfusion syndrome (RPS). One-year, 3-year, and 5-year incidences of ischemic cholangiopathy (IC) did not differ significantly in DBD cases between the NMP and ICS cohorts. In DCD LT, NMP was an independent protective factor against EAD [0.11 (0.03-0.46)] and RPS [0.04 (0.01-0.25)]. The incidence of IC in the DCD cases at 1-year and 3-year time points was significantly lower in the NMP cohort (1.9% compared with 20% in the ICS group). Compared with conventional ICS, NMP can significantly reduce the incidence of EAD, RPS, and IC after DCD LT.

Circulating exosomes from brain death and cardiac death donors have distinct molecular and immunologic properties: A pilot study.

Comparison of donation after brain death (DBD) and donation after cardiac death (DCD) lung tissue before transplantation have demonstrated activation of pro-inflammatory cytokine pathway in DBD donors. The molecular and immunological properties of circulating exosomes from DBD and DCD donors were not previously described. We collected plasma from 18 deceased donors (12 DBD and six DCD). Cytokines were analyzed by 30-Plex luminex Panels. Exosomes were analyzed for liver self-antigen (SAg), Transcription Factors and HLA class II (HLA-DR/DQ) using western blot. C57BL/6 animals were immunized with isolated exosomes to determine strength and magnitude of immune responses. Interferon (IFN)-γ and tumor necrosis factor-α producing cells were quantified by ELISPOT, specific antibodies to HLA class II antigens were measured by ELISA RESULTS: We demonstrate increased plasma levels of IFNγ, EGF, EOTAXIN, IP-10, MCP-1, RANTES, MIP-β, VEGF, and interleukins - 6/8 in DBD plasma versus DCD. MiRNA isolated from exosome of DBD donors demonstrated significant increase in miR-421, which has been reported to correlate with higher level of Interleukin-6. Higher levels of liver SAg Collagen III (p=.008), pro-inflammatory transcription factors (NF-κB, p<.05; HIF1α, p=.021), CIITA (p=.011), and HLA class II (HLA-DR, p=.0003 and HLA-DQ, p=.013) were detected in exosomes from DBD versus DCD plasma. The circulating exosomes isolated from DBD donors were immunogenic in mice and led to the development of Abs to HLA-DR/DQ. This study provides potential new mechanisms by which DBD organs release exosomes that can activate immune pathways leading to cytokine release and allo-immune response.

CARC18: Donor Heart Refusal Following Circulatory Death: An Analysis Of UNOS Refusal Codes

Purpose: Due to the severe shortage of donor hearts, many patients with end-stage cardiac disease die before receiving potentially lifesaving transplantation. In the past, heart donation was restricted to donation after brain death (DBD). Utilizing hearts following controlled donation after circulatory determined death (DCD) is a promising development that could significantly increase the number of hearts available for transplantation. Recent studies demonstrate that survival following transplantation of controlled DCD hearts achieves results similar to transplantation using DBD hearts. Currently, the majority of DCD hearts are discarded because most do not meet the strict criteria required for controlled DCD. Of those that meet controlled DCD criteria, the majority are still refused by the recipient institutions. We sought to explore this discrepancy and characterize the reasons that institutions refuse hearts that appear to meet controlled DCD criteria. Methods: All United Network for Organ Sharing (UNOS) refusal codes used for both DCD and DBD donors in the United States for the years 2021 and 2022 were compiled and analyzed. Rates of donor heart refusal were compared using a Z-test. Odds ratios (OR) with 95% confidence intervals (CI) were calculated to characterize the basis for DCD heart refusal. Results: During the study period 83.3% (2,578/3,094) of potential DCD hearts were declined for transplantation, while 35.5% (3,770/10,610) of potential DBD hearts were declined (p<0.01). Specifically, in 2022 refusal code data demonstrated that DCD hearts were more likely to be declined due to prolonged warm ischemic time than DBD hearts (OR 2.781; 95% CI, 4.253-1.818; p<0.01) and more likely to be declined due to organ preservation concerns (OR 1.612; 95% CI, 2.044-1.272; p<0.01). The most frequently used refusal code for DCD hearts was neurological function. In 2022, 29% (24,989/86,196) of all DCD refusals were attributed to neurological function, presumably because retained neurological function prolonged the period of warm ischemia. Conclusion: The high DCD refusal rates do not appear to align with previous publications showing that results following transplantation of controlled DCD hearts are similar to DBD. Further analysis of transplant recipient team criteria that result in DCD heart refusal should be considered. Understanding and addressing the specific reasons for refusal may substantially increase the number of donor hearts available for transplantation.

Outcomes of lung and liver transplantation after simultaneous recovery using abdominal normothermic regional perfusion in donors after the circulatory determination of death versus donors after brain death

Normothermic regional perfusion (NRP) in controlled donation after the circulatory determination of death (cDCD) is a growing preservation technique for abdominal organs that coexists with the rapid recovery of lungs. We aimed to describe the outcomes of lung transplantation (LuTx) and liver transplantation (LiTx) when both grafts are simultaneously recovered from cDCD donors using NRP and compare them with grafts recovered from donation after brain death (DBD) donors. All LuTx and LiTx meeting these criteria during January 2015 to December 2020 in Spain were included in the study. Simultaneous recovery of lungs and livers was undertaken in 227 (17%) donors after cDCD with NRP and 1879 (21%) DBD donors (P < .001). Primary graft dysfunction grade-3 within the first 72 hours was similar in both LuTx groups (14.7% cDCD vs. 10.5% DBD; P = .139). LuTx survival at 1 and 3 years was 79.9% and 66.4% in cDCD vs. 81.9% and 69.7% in DBD (P = .403). The incidence of primary nonfunction and ischemic cholangiopathy was similar in both LiTx groups. Graft survival at 1 and 3 years was 89.7% and 80.8% in cDCD vs. 88.2% and 82.1% in DBD LiTx (P = .669). In conclusion, the simultaneous rapid recovery of lungs and preservation of abdominal organs with NRP in cDCD donors is feasible and offers similar outcomes in both LuTx and LiTx recipients to transplants using DBD grafts.

A national pilot of donation after circulatory death (DCD) heart transplantation within the United Kingdom

The United Kingdom (UK) was one of the first countries to pioneer heart transplantation from donation after circulatory death (DCD) donors. To facilitate equity of access to DCD hearts by all UK heart transplant centers and expand the retrieval zone nationwide, a Joint Innovation Fund (JIF) pilot was provided by NHS Blood and Transplant (NHSBT) and NHS England (NHSE). The activity and outcomes of this national DCD heart pilot program are reported. This is a national multi-center, retrospective cohort study examining early outcomes of DCD heart transplants performed across 7 heart transplant centers, adult and pediatric, throughout the UK. Hearts were retrieved using the direct procurement and perfusion (DPP) technique by 3 specialist retrieval teams trained in ex-situ normothermic machine perfusion. Outcomes were compared against DCD heart transplants before the national pilot era and against contemporaneous donation after brain death (DBD) heart transplants, and analyzed using Kaplan-Meier analysis, chi-square test, and Wilcoxon's rank-sum. From September 7, 2020 to February 28, 2022, 215 potential DCD hearts were offered of which 98 (46%) were accepted and attended. There were 77 potential donors (36%) which proceeded to death within 2 hours, with 57 (27%) donor hearts successfully retrieved and perfused ex situ and 50 (23%) DCD hearts going on to be transplanted. During this same period, 179 DBD hearts were transplanted. Overall, there was no difference in the 30-day survival rate between DCD and DBD (94% vs 93%) or 90 day survival (90% vs 90%) respectively. There was a higher rate of ECMO use post-DCD heart transplants compared to DBD (40% vs 16%, p=0.0006), and DCD hearts in the pre pilot era, (17%, p=0.002). There was no difference in length of ICU stay (9 DCD vs 8 days DBD, p=0.13) nor hospital stay (28 DCD vs 27 DBD days, p=0.46). During this pilot study, 3 specialist retrieval teams were able to retrieve DCD hearts nationally for all 7 UK heart transplant centers. DCD donors increased overall heart transplantation in the UK by 28% with equivalent early posttransplant survival compared with DBD donors.

Extended criteria brain-dead organ donors: Prevalence and impact on the utilisation of livers for transplantation in Brazil.

Despite its association with higher postoperative morbidity and mortality, the use of extended criteria donor (ECD) livers for transplantation has increased globally due to the high demand for the procedure. To investigate the prevalence of ECD in donation after brain death (DBD) and its impact on organ acceptance for transplantation. Retrospective analysis of DBD organ offers for liver transplantation between 2017 and 2020 in a high-volume transplant centre. The incidence of the Eurotransplant risk factors to define an ECD (ET-ECD) among DBD donors and the likelihood of organ acceptance over the years were analysed. The relationship between organ refusal for transplantation, the occurrence, and the number of ET-ECD was assessed by simple and multiple logistic regression adjustment. A total of 1619 organ donors were evaluated. Of these, 78.31% (n = 1268) had at least one ET-ECD criterion. There was an increase in the acceptance of ECD DBD organs for transplantation (1 criterion: from 23.40% to 31.60%; 2 criteria: from 13.10% to 27.70%; 3 criteria: From 6.30% to 13.60%). For each addition of one ET-ECD variable, the estimated chance of organ refusal was 64.4% higher (OR 1.644, 95%CI 1.469-1.839, P < 0.001). Except for the donor serum sodium > 165 mmol/L (P = 0.310), all ET-ECD criteria increased the estimated chance of organ refusal for transplantation. A high prevalence of ECD DBD was observed. Despite the increase in their utilisation, the presence and the number of extended donor criteria were associated with an increased likelihood of their refusal for transplantation.

The impact of geographic location versus center practice on center volume in liver transplantation after the acuity circle policy.

The allocation system for livers used the acuity circles (AC) beginning in 2020. In this study, we sought to evaluate the effect of the AC policy on center transplant volumes, from geographic and center practice perspectives. Using the US national registry data between 2018 and 2022, adult liver transplantations (LTs) were separated into two eras: before AC and after AC. The number of LT for Model for End-Stage Liver Disease (MELD) scores ≥29 have significantly increased by 10%, and waitlist times for those patients have been significantly shorter after AC. These benefits were not found in patients with MELD scores<29. The geographic distribution of transplant centers reveals that the majority of centers which increased their transplant volume (18 out of 25 centers) are located in high-population states while there are seven transplant centers in nonhigh-population states. The centers in the nonhigh-population states utilized more marginal donation after brain death (DBD) and donation after circulatory death (DCD) donors by 27% and 155%, respectively. MELD scores were significantly lower in the nonhigh-population states compared with those in the high-population states (p<.01). AC improved the LT access for patients with MELD scores ≥29, which benefited the high-population states. However, aggressive center practices to utilize marginal DBD and DCD donors were able to increase transplant volume and lower median allocation MELD scores.

Organ donation after cardiac death in Japan

In Japan, since the revision of the Organ Transplant Law in July 2010, donation after brain death (DBD) has increased, while donation after cardiac death (DCD), which has been mainly used by kidney transplantation, has decreased. The number of DCD donors decreased from 98 in 2009 to 28 in 2019. There is no clear reason for the decrease in DCD donors. Furthermore, since 2020, there has been a marked decrease in DCD due to the influence of the COVID-19 pandemic. On the other hand, the outcomes after kidney transplantation from DCD donors are improving year by year. The outcomes of kidney transplantation from DCD donors in Japan are comparable to those of kidney transplantation from DBD donors in Western countries. In order to further improve transplantation outcomes from DCD donors, the clinical introduction of continuous machine perfusion preservation technology, for the purpose of reducing ischemic reperfusion injury, is expected in Japan.

313.6: Early Graft Disfunction After Hypothermic Oxygenated Machine Perfusion of ECD Criteria Liver Grafts: No Longer A Clinical Issue?

Introduction: Early allograft disfunction (EAD) continues to be an important issue in liver transplantation, varying from 15 to 30%. This rate is particularly high in case of extended criteria donor (ECD) grafts due to significant ischemia-reperfusion injury leading to EAD. This injury is substantially reduced by thermoregulated oxygenated machine perfusion. The aim of the paper was to assess the use of hypothermic oxygenated machine perfusion (HOPE) in ECD liver grafts in a high-volume liver transplantation center using a specific protocol. Method: Grafts with >30% macrosteatosis and with multiple ECD (at least 2 criteria) were perfused using dual HOPE (hepatic artery and portal vein perfusion), while HOPE (portal vein perfusion only) was used for the remaining ECD grafts. The main criteria to establish graft improvement were the improvement of arterial and portal perfusion flows, with lactate under 3 mmol/L throughout the procedure. Results: Between February 2016 and February 2022, 26 ECD liver grafts were harvested from DBD (donation after brain death) donors and benefitted from HOPE. Dual HOPE was used in 8 grafts (30.7%). Criteria for graft improvement were met in all grafts except 5 (19.2%), where lactate was over 3 mmol/L, with a median of 3.6 (range 3.5-6.1). The median follow-up was 5 months (range 2-44). No EAD was encountered. Conclusion: By using a combined protocol of HOPE and dual HOPE, ECD liver grafts may be safely used by avoiding early graft dysfunction.

411.6: Inferior Long-term Outcomes of Simultaneous Liver-Kidney Transplantation Using Donation After Cardiac Deaths Donors in the United Network for Organ Sharing Database

Background: Outcomes of simultaneous liver-kidney transplantation (SLKT) in donation after cardiac death (DCD) have improved over the years, but data are limited. Aim of this study was to assess the long-term outcomes of SLKT from DCD organs and then compare them to donation after brain death (DBD) organs. Methods: We analyzed data from the United Network for Organ Sharing (UNOS) from 2002 to 2021. Adult SLKT were included, other multi-organ and re-transplants were excluded from the analysis. Propensity score matching was performed to assess the outcomes between two groups. P<0.05 was considered as significant. Results: In the United States, 8733 SLKT were performed during the study period (499 SLKT from DCD and 8234 from DBD). Recipients of DCD organs, when compared to recipients of DBD organs, were older (median age 59 vs 58 years, P=0.005), had lower prevalence of dialysis (62 vs 68%, P=0.003), lower Model for End-Stage Liver Disease (MELD) score (24 vs 29, P<0.001) and longer wait-time (89 vs 68 days, P=0.009). Donors of DCD organs were younger (median age 33 vs 35 years, P<0.001), had shorter cold ischemia time in liver (5.8 vs 6.0 hours, P<0.001) and in kidney (9.5 vs 10.5 hours, P<0.001), and had similar kidney donor profile index (31 vs 30 %, P=0.18) compared to DBD donor. The most common primary diagnosis for both recipient groups was alcohol-related liver disease, while non-alcoholic steatohepatitis was more common in DCD group (28 vs 21%). Long-term outcomes including five-year overall survival and liver graft survivals were inferior in DCD recipients (71.4 vs 74.8%, P=0.11; 74.0 vs 67.1%, P=0.0011). After propensity score matching, five-year overall survival and liver graft survivals were inferior (71.4 vs 76.4%, P=0.031; 67.1 vs 76.0%, P<0.001). Multivariable cox-regression analysis in the matched-cohort showed that DCD was an independent risk factor of mortality (hazard ratio {HR}- 1.33; 95% Confidence interval{CI}, 1.04-1.68; P=0.021) and liver graft failure (HR- 1.54; 95% CI, 1.24-1.92; P<0.001). For kidney allograft outcomes in matched-cohort, delayed graft function was higher in DCD (36 vs 20%, P<0.001) and five-year kidney graft outcome was inferior in DCD (67.3 vs 74.7%, P=0.0034). The most common listed causes of five-year mortality were infection (21.4%) and multi-organ failure (20.8%) and there were no differences between two groups. Other factors associated with mortality were recipient older age (HR 1.03; 95%CI 1.02-1.04, P<0.001), male recipient (HR 1.32; 95%CI 1.06-1.64, P=0.014), and donor older age (HR 1.01; 95%CI 1.00-1.02, P=0.024). Conclusion: Recipients of SLKT from DCD donors had inferior long-term post-transplant outcomes with decrease in overall survival and allograft survival. Careful identification of risk factors associated with worse outcomes is required to improve utilization of DCD donors for SLKT.

400.5: Outcomes After Declining a Donation After Cardiac Death (DCD) Liver for Transplant Candidates in the United States

Introduction: In the context of the deceased-donor liver shortage, donation after cardiac death (DCD) provides an opportunity to expand the donor pool, but DCD organs confer higher risk of biliary complications and graft loss. Patients and clinicians who are offered a DCD liver must choose whether to accept the higher risk or remain on the waitlist in hopes of a better offer. We explored outcomes of candidates who declined a DCD offer, and investigated the survival benefit accepting vs declining the offer of a DCD liver. In addition, we estimated the number of additional liver transplants that could be achieved if DCD livers were utilized at the same rate as livers from otherwise-comparable DBD donors. Methods: Using national registry data from the United States (SRTR) 2009-2020, we identified 1,564 candidates who accepted DCD offers (“acceptors”) and 16,981 candidates who declined the same DCD offers (“decliners”). We characterized outcomes of decliners using a competing risk framework. In addition, we compared patient survival of acceptors vs. decliners using Cox regression. We used Poisson regression to compare observed discard of DCD livers to the number of discards expected based on donor characteristics other than DCD. Results: Among DCD decliners, 50.9% died/dropped out from waitlist; only 43.1% were transplanted with a donation after brain death (DBD) liver. DCD acceptors had lower mortality compared to decliners at 10 years post-offer (35.4% vs. 48.9%, p<0.001) (Fiigure 1). After adjustment, DCD acceptors had 46% lower mortality risk compared to DCD decliners (aHR= 0.49 0.54 0.61). The survival benefit of DCD LT varied by MELD stratum. DCD acceptors and decliners with MELD 6-14 at offer had comparable risk of mortality (aHR= 0.56 0.89 1.42, p=0.6). DCD offer acceptors had 55%, 34% and 52% lower risk of mortality compared to DCD offer decliners within MELD strata 15-24 (aHR= 0.39 0.45 0.54, p<0.001), 25-34 (aHR= 0.55 0.66 0.79, p<0.001) and 35 or higher (aHR= 0.29 0.48 0.78, p=0.004), respectively (Figure 2). Out of 1005 recovered DCD livers, 298 were discarded in 2019. If DCD livers were utilized at the same rate as comparable DBD livers, we estimated that 235 (78.9%) of them would have been transplanted. Conclusions: Despite risk of biliary complications, DCD offer acceptance is associated with considerable long-term survival benefit for liver transplant candidates. Increased utilization of DCD livers should be encouraged. This work was supported by grant number K01DK101677 (Massie), 5T32DK007713-23 (Eagleson), and K24DK101828 (Segev) from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The analyses described here are the responsibility of the authors alone and do not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the U.S. Government. The data reported here have been supplied by the Hennepin Healthcare Research Institute (HHRI) as the contractor for the Scientific Registry of Transplant Recipients (SRTR). The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy of or interpretation by the SRTR or the U.S. Government.