Donation After Circulatory Death Grafts Research Articles

Dexmedetomidine and argon in combination against ferroptosis through tackling TXNIP-mediated oxidative stress in DCD porcine livers

Graft availability from donation after circulatory death (DCD) is significantly limited by ischaemia reperfusion (IR) injury. Effective strategies to mitigate IR injury in DCD grafts are essential to improve graft quality and expand the donor pool. In this study, liver grafts from DCD pigs were preserved in the University of Wisconsin (UW) solution saturated with 0.1 nM dexmedetomidine (Dex) and various concentrations of noble gases Argon (Ar) and/or Xenon (Xe) at 4 °C for 24 or 72 h. The combined 50% Ar and Dex provided maximum protection to liver grafts by reducing morphological damage, apoptosis, necroptosis, ferroptosis, hepatocyte glycogen depletion, reticulin framework collapse, iron deposition, and oxidative stress. In vitro, human liver Hep G2 cells were preserved in the UW solution saturated with 0.1 nM Dex and 50% Ar in combination at 4 °C for 24 h, followed by recovery in medium at 37 °C for up to 48 h to mimic clinical IR injury. This treatment significantly increased the expression of anti-oxidative stress proteins by promoting the translocation of thioredoxin-interacting protein (TXNIP) to mitochondria, thereby inhibiting ferroptosis, increasing plasma membrane integrity, and maintaining cell viability.In summary, The combination of 0.1 nM Dex and 50% Ar may be a promising strategy to reduce ferroptosis and other form cell death, and preserve liver grafts.

Subnormothermic Oxygenated Machine Perfusion (24 h) in DCD Kidney Transplantation.

Ex vivo kidney perfusion is an evolving platform that demonstrates promise in preserving and rehabilitating the kidney grafts. Despite this, there is little consensus on the optimal perfusion conditions. Hypothermic perfusion offers limited functional assessment, whereas normothermic perfusion requires a more complex mechanical system and perfusate. Subnormothermic machine perfusion (SNMP) has the potential to combine the advantages of both approaches but has undergone limited investigation. Therefore, the present study sought to determine the suitability of SNMP for extended kidney preservation. SNMP at 22-25 °C was performed on a portable device for 24 h with porcine kidneys. Graft assessment included measurement of mechanical parameters and biochemical analysis of the perfusate using point-of-care tests. To investigate the viability of kidneys preserved by SNMP, porcine kidney autotransplants were performed in a donation after circulatory death (DCD) model. SNMP was also compared with static cold storage (SCS). Finally, follow-up experiments were conducted in a subset of human kidneys to test the translational significance of findings in porcine kidneys. In the perfusion-only cohort, porcine kidneys all displayed successful perfusion for 24 h by SNMP, evidenced by stable mechanical parameters and biological markers of graft function. Furthermore, in the transplant cohort, DCD grafts with 30 min of warm ischemic injury demonstrated superior posttransplant graft function when preserved by SNMP in comparison with SCS. Finally, human kidneys that underwent 24-h perfusion exhibited stable functional and biological parameters consistent with observations in porcine organs. These observations demonstrate the suitability and cross-species generalizability of subnormothermic machine perfusion to maintain stable kidney perfusion and provide foundational evidence for improved posttransplant graft function of DCD kidneys after SNMP compared with SCS.

Financial impact of donation after circulatory death heart transplantation: A single-center analysis.

Clinical success of donation after circulatory death (DCD) heart transplantation is leading to growing adoption of this technique. In comparison to procurement from a brain-dead donor, DCD requires additional resources. The economic impact of DCD heart transplantation from the hospital perspective is not well known. We compared the financial data of patients who received DCD allografts to those who received a DBD organ at our institution from January 1, 2021 to December 31, 2022. We also compared the cost of ex-situ machine perfusion to in-situ organ perfusion employed during DCD recovery. We performed 58 DBD and 22 DCD heart-alone transplantations during the study period. Out of 22 DCD grafts, 16 were recovered with thoracoabdominal normothermic regional perfusion (TA-NRP) and six with direct procurement followed by normothermic machine perfusion (DP-NMP). The contribution margin per case for DBD versus DCD was $234,362 and $235,440 (P=.72). The direct costs did not significantly differ between the two groups ($171,949 and 186,250; P=.49). In comparing the two methods of procuring hearts from DCD donors, the direct cost of TA-NRP was $155,955 in comparison to $223,399 for DP-NMP (P=.21). This difference translated into a clinically meaningful but not statistically significant greater contribution margin for TA-NRP ($242, 657vs. $175,768; P=.34). Our data showed that the adoption of DCD procurement did not have a negative financial impact on the contribution margin in our institution. Programs considering starting DCD heart transplantation, and those who are currently performing DCD procurement should evaluate their own financial situation.

Outcomes of liver transplantation for hepatocellular carcinoma in donation after circulatory death compared with donation after brain death: A systematic review and meta-analysis

Introduction and ObjectivesDue to organ shortages, liver transplantation (LT) using donation-after-circulatory-death (DCD) grafts has become more common. There is limited and conflicting evidence on LT outcomes using DCD grafts compared to those using donation-after-brain death (DBD) grafts for patients with hepatocellular carcinoma (HCC). We aimed to summarize the current evidence on the outcomes of DCD-LT and DBD-LT in patients with HCC. Materials and MethodsOnline databases were searched for studies comparing DCD-LT and DBD-LT outcomes in patients with HCC and a meta-analysis was conducted using fixed- or random-effects models. ResultsFive studies involving 487 (33.4%) HCC DCD-LT patients and 973 (66.6%) DBD-LT patients were included. The meta-analysis showed comparable 1-year [relative risk (RR)=0.99, 95%CI:0.95 to 1.03, p=0.53] and 3-year [RR=0.99, 95%CI:0.89 to 1.09, p=0.79] recurrence-free survival. The corresponding 1-year [RR=0.98, 95%CI:0.93 to 1.03, p=0.35] and 3-year [RR=0.94, 95%CI:0.87 to 1.01, p=0.08] patient survival and 1-year [RR=0.91, 95%CI:0.71 to 1.16, p=0.43] and 3-year [RR=0.92, 95%CI:0.67 to 1.26, p=0.59] graft survival were also comparable. There were no significant differences between the two cohorts regarding the tumor characteristics, donor/recipient risk factors and the incidence of post-operative complications, including acute rejection, primary non-function, biliary complications and retransplantation. ConclusionsBased on the current evidence, it has been found that comparable outcomes can be achieved in HCC patients using DCD-LT compared to DBD-LT, particularly when employing good quality graft, strict donor and recipient selection, and effective surgical management. The decision to utilize DCD-LT for HCC patients should be personalized, taking into consideration the risk of post-LT HCC recurrence. (PROSPERO ID: CRD42023445812).

Modern-Day Practice of DCD Liver Transplantation: Controversies, Innovations, and Future Directions.

Over the past decade, donation after circulatory death (DCD) liver transplantation has expanded in the United States due to improved surgical experience and perioperative management. Despite these advances, there remains a reluctance towards broader utilization of DCD liver allografts due to lack of standardized donation process, concern for inferior graft survival, and risk of ischemic cholangiopathy associated with temporary lack of oxygenated perfusion during withdrawal of life-supporting treatment during procurement. New perfusion technologies offer potential therapeutic options to mitigate biliary complications and expand utilization of marginal DCD grafts. As these modalities enter routine clinical practice, DCD utilization will continue to increase, and liver allocation policies in turn will evolve to reflect this growing practice. This review describes recent progress in DCD LT, current challenges with utilization of DCD liver allografts, and how novel technologies and policies could impact the future of the field.

Utilization of Paragonix Sherpapak Cardiac Transport System for the Preservation of Donor Hearts After Circulatory Death

Donation after circulatory death (DCD) heart transplantation is being increasingly adopted by transplant centers. The optimal method of DCD heart preservation during transport after in situ thoracoabdominal normothermic regional perfusion (TA-NRP) is not known. We evaluated our experience with the Paragonix SherpaPak Cardiac Transport System (SCTS) for the transport of DCD cardiac allografts after TA-NRP recovery between January 2021 and December 2022. We collected and evaluated donor characteristics, allograft ischemic intervals, and recipient baseline demographic and clinical variables, and short-term outcomes. Twelve recipients received DCD grafts recovered with TA-NRP and transported in SCTS during the study period. The median age of 10 male and 2 female donors was 32 years (min 15, max 38). The median duration of functional warm ischemia was 12 minutes (min 8, max 22). Hearts were preserved in SCTS for a median of 158 minutes (min 37, max 224). Median recipient age was 61 years (min 28, max 70). Ten recipients (83%) survived to hospital discharge, with one death attributable to graft dysfunction (8%). The median vasoactive-inotropic (VIS) score at 72 hours post-transplantation of the entire cohort was 6 (min 0, max 15). The median length of intensive care unit stay in hospital survivors was 5 days (min 3, max 17) days and hospital stay 17 days (min 9, max 37). The Paragonix SCTS provides efficacious preservation of DCD grafts for ≥3.5 hours. Organs transported with this device showed satisfactory post-transplantation function.

Kidney Donation After Circulatory Death Using Thoracoabdominal Normothermic Regional Perfusion: The Largest Report of the United States Experience.

Thoracoabdominal normothermic regional perfusion (TA-NRP) has been increasingly used for donation after circulatory death (DCD) procurements in the United States. We present the largest report of outcomes of kidney transplants performed using DCD donor grafts perfused with TA-NRP. Adult DCD kidney transplants between 2020 and 2022 in the United Network for Organ Sharing database were included. Donors with ≥50 min between asystole and aortic cross-clamp time in which the heart was also transplanted were considered TA-NRP donors. All other donors were considered direct recovery donors. Multivariable regressions were used to assess delayed graft function, as well as posttransplant survival and all-cause graft failure at 30, 90, and 180 d. A propensity-matched analysis of cohorts matched on donor Kidney Donor Profile Index was performed. Of the 16 140 total DCD kidney transplants performed during the study period, 306 (1.9%) used TA-NRP. TA-NRP donors were younger ( P < 0.001) and had lower Kidney Donor Profile Index ( P < 0.001) compared with direct recovery donors. Recipients receiving grafts recovered using TA-NRP were younger ( P < 0.001) and more likely to be blood group O ( P < 0.001). Transplants using TA-NRP had lower likelihood of delayed graft function (adjusted odds ratio 0.22 [95% confidence interval, 0.15-0.31], P < 0.001) but similar 180-d survival ( P = 0.8) and all-cause graft failure ( P = 0.3) as transplants using direct recovery grafts. These inferences were unchanged on propensity-matched analysis. Our results demonstrate that kidney transplants using TA-NRP DCD allografts have positive short-term mortality and graft survival outcomes, with significantly decreased rates of delayed graft function compared with direct recovery DCD grafts.

DCD liver transplant in patients with a MELD over 35.

Donation after circulatory death (DCD) liver transplantation (LT) makes up well less than 1% of all LTs with a Model for End-Stage Liver Disease (MELD)≥35 in the United States. We hypothesized DCD-LT yields acceptable ischemia-reperfusion and reasonable outcomes for recipients with MELD≥35. We analyzed recipients with lab-MELD≥35 at transplant within the UCSF (n=41) and the UNOS (n=375) cohorts using multivariate Cox regression and propensity score matching. In the UCSF cohort, five-year patient survival was 85% for DCD-LTs and 86% for matched-Donation after Brain Death donors-(DBD) LTs (p=0.843). Multivariate analyses showed that younger donor/recipient age and more recent transplants (2011-2021 versus 1999-2010) were associated with better survival. DCD vs. DBD graft use did not significantly impact survival (HR: 1.2, 95%CI 0.6-2.7). The transaminase peak was approximately doubled, indicating suggesting an increased ischemia-reperfusion hit. DCD-LTs had a median post-LT length of stay of 11 days, and 34% (14/41) were on dialysis at discharge versus 12 days and 22% (9/41) for DBD-LTs. 27% (11/41) DCD-LTs versus 12% (5/41) DBD-LTs developed a biliary complication (p=0.095). UNOS cohort analysis confirmed patient survival predictors, but DCD graft emerged as a risk factor (HR: 1.5, 95%CI 1.3-1.9) with five-year patient survival of 65% versus 75% for DBD-LTs (p=0.016). This difference became non-significant in a sub-analysis focusing on MELD 35-36 recipients. Analysis of MELD≥35 DCD recipients showed that donor age of <30yo independently reduced the risk of graft loss by 30% (HR, 95%CI: 0.7 (0.9-0.5), p=0.019). Retransplant status was associated with a doubled risk of adverse event (HR, 95%CI: 2.1 (1.4-3.3), p=0.001). The rejection rates at 1y were similar between DCD- and DBD-LTs, (9.3% (35/375) versus 1,541 (8.7% (1,541/17,677), respectively). In highly selected recipient/donor pair, DCD transplantation is feasible and can achieve comparable survival to DBD transplantation. Biliary complications occurred at the expected rates. In the absence of selection, DCD-LTs outcomes remain worse than those of DBD-LTs.

Metabolic Outcomes After Pancreas Transplant Alone From Donation After Circulatory Death Donors-The UK Transplant Registry Analysis.

Extrapolating data from early DCD (donation after circulatory death) kidney transplantation, pancreas transplants from DCD grafts were feared to have worse metabolic outcomes. Hence, we aimed to address the question of pancreas transplant alone (PTA) from DCD donors-are our concerns justified? A UK transplant registry analysis of 185 PTA performed between 2005 and 2018 was done. All early graft losses (<3months) were excluded to allow focus on the metabolic outcomes (HbA1c, weight gain and incidence of secondary diabetic macrovascular complications). The aim was to compare the metabolic outcomes, rejection rates (including the need for steroids), patient and graft survival between DBD (Donation after brainstem death) and DCD groups. After excluding early graft losses, data from 162 PTA (DBD = 114 and DCD = 48) were analyzed. Body mass index of the donor was less in DCD group (DBD = 23.40 vs. DCD = 22.25, p = 0.006) and the rest of the baseline transplant characteristics were comparable. There were no significant differences in the HbA1c, weight gain, rejection rate, and incidence of secondary diabetic macrovascular complications post-transplant between DBD and DCD recipients. The 1-, 5-, and 10-year patient and graft survival were similar in both the groups. PTA from DCD donors have equivalent metabolic outcomes and survival (patient/graft) as that of DBD donors.

Expanding Liver Transplant Opportunities in Older Patients With Nonconventional Grafts

IntroductionBroader use of donation after circulatory death (DCD) and nonconventional grafts for liver transplant helps reduce disparities in organ availability. Limited data, however, exists on outcomes specific to nonconventional graft utilization in older patients. As such, this study aimed to investigate outcomes specific to conventional and nonconventional graft utilization in recipients > 70 y of age. Methods1-to-3 matching based on recipient sex, Model for End-Stage Liver Disease score, and donor type was performed on patients ≥70 and <70 y of age who underwent liver transplant alone at Mayo Clinic Arizona between 2015 and 2020. Primary outcomes were posttransplant patient and liver allograft survival for recipients greater than or less than 70 y of age. Secondary outcomes included grafts utilization patterns, hospital length of stay, need for reoperation, biliary complications and disposition at time of hospital discharge. ResultsIn this cohort, 36.1% of grafts came from DCD donors, 17.4% were postcross clamp offers, and 20.8% were nationally allocated. Median recipient ages were 59 and 71 y (P < 0.01). Recipients had similar Intensive care unit (P = 0.82) and hospital (P = 0.14) lengths of stay, and there were no differences in patient (P = 0.68) or graft (P = 0.38) survival. When comparing donation after brain death and DCD grafts in those >70 y, there were no differences in patient (P = 0.89) or graft (P = 0.71) survival. ConclusionsExcellent outcomes can be achieved in older recipients, even with use of nonconventional grafts. Expanded use of nonconventional grafts can help facilitate transplant opportunities in older patients.

Lung Transplantation From Controlled and Uncontrolled Donation After Circulatory Death (DCD) Donors With Long Ischemic Times Managed by Simple Normothermic Ventilation and Ex-Vivo Lung Perfusion Assessment.

Donation after cardiac death (DCD) donors are still subject of studies. In this prospective cohort trial, we compared outcomes after lung transplantation (LT) of subjects receiving lungs from DCD donors with those of subjects receiving lungs from donation after brain death (DBD) donors (ClinicalTrial.gov: NCT02061462). Lungs from DCD donors were preserved in-vivo through normothermic ventilation, as per our protocol. We enrolled candidates for bilateral LT ≥14years. Candidates for multi-organ or re-LT, donors aged ≥65years, DCD category I or IV donors were excluded. We recorded clinical data on donors and recipients. Primary endpoint was 30-day mortality. Secondary endpoints were: duration of mechanical ventilation (MV), intensive care unit (ICU) length of stay, severe primary graft dysfunction (PGD3) and chronic lung allograft dysfunction (CLAD). 121 patients (110 DBD Group, 11 DCD Group) were enrolled. 30-day mortality and CLAD prevalence were nil in the DCD Group. DCD Group patients required longer MV (DCD Group: 2days, DBD Group: 1 day, p = 0.011). ICU length of stay and PGD3 rate were higher in DCD Group but did not significantly differ. LT with DCD grafts procured with our protocols appears safe, despite prolonged ischemia times.

Addressing inadequate blood flow during normothermic regional perfusion for in-situ donation after circulatory death grafts preservation.

Donation after circulatory death (DCD) has emerged as attainable strategy to tackle the issue of organ shortage, expanding the donor pool. The DCD concept has been applied to the multiple declinations of circulatory arrest, as per the Modified Maastricht Classification. Notwithstanding, whichever the scenario, DCD donors experience a variable warm ischemia time whose correlation with graft dysfunction is ascertained. This applies to both "controlled" (cDCD) donors (i.e., the timespan from the withdrawal of life-sustaining therapies to the onset of in-situ perfusion), and "uncontrolled" DCD (uDCD) (i.e., the low-flow period during cardiopulmonary resuscitation - CPR). This sums up to the no-flow time from cardiac arrest to the start of CPR for uDCD donors, and to the no-touch period for both uDCDs and cDCDs. Static and hypothermic storage may not be appropriate for DCD grafts. In order to overcome this ischemic insult, extracorporeal membrane oxygenation devices are adopted to guarantee the in-situ grafts preservation by means of techniques such as the normothermic regional perfusion (NRP) which consists in a selective abdominal perfusion obtained via the endovascular or surgical occlusion of the thoracic aorta. The maintenance of an adequate pump flood throughout NRP is therefore a sine qua non to accomplish the DCD donation. The issue of insufficient pump flow during NRP is prevalent and clinically significant but its management remains technically challenging and not standardized. Hereby we propose a systematic algorithmic approach to address this relevant occurrence.

Donation after Circulatory Death Grafts Have Comparable Outcomes to Donation after Brain Death Grafts in Liver Transplantation

Introduction: In the United States, 30% of donation after circulatory death (DCD) grafts are discarded for liver transplantation (LT). DCD grafts can mitigate liver organ shortage but is underused due to the believe of poor outcomes in graft and patient survival. Recent studies have shown comparable outcomes to donation after brain death (DBD). The aim of this study is to review our experience with the use of DCD grafts. Methods: Retrospective single center study, whole grafts transplanted between January 2014 and December 2021 were included. Propensity score match was done using recipient age, recipient gender, MELD score, wait time, number of previous LT, cold ischemia time, year of LT and surgeon as cofounders. Multivariate Cox-regression models were created with significant variables in the univariate analysis. Finally, Kaplan-Meier curves with log-rank test were performed. Results: A total of 63 DCD and 148 DBD grafts were included. The patients were predominantly males (59.2%), median age was 58 (IQR 49-65), the most common reason for transplantation was alcoholic cirrhosis (20.4%) and were listed for their first LT (95.7%). Number of transplants (HR:15.39, 95%CI: 3.56-66.49, p < 0.001) and BMI (HR:1.1, 95%CI: 1.01-1.2, p = 0.03) were associated to graft loss. DCD was not associated with graft (HR:0.47, 95%CI: 0.14-1.58, p = 0.2) or patient (HR:0.33, 95%CI: 0.08-1.42, p = 0.1) survival. Graft (92.9% DBD vs 96.8% DCD, p = 0.2) and patient (93.6% DBD vs 100% DCD, p = 0.1) 2-year survival were similar. Conclusion: When matching different cofounders, the use of DCD grafts has comparable outcomes to those DBD grafts.

Comparison of Outcomes in High Donation after Circulatory Death Liver Transplantation Usage Centers in the Acuity Circles Era

INTRODUCTION: The recent acuity circles (AC) liver allocation policy has increased rates of donation after circulatory death (DCD) liver transplantation. We hypothesize that transplant centers with high-volume DCD graft usage may have differing outcomes. METHODS: All adult DCD transplant recipients in the United Network for Organ Sharing (UNOS) STAR file from January 11, 2016, to September 30, 2021, were included. Living liver grafts, pediatric, and nonkidney simultaneous transplantation were excluded. The top decile of DCD transplant centers by volume per year were identified. Six-month and 1-year patient and liver graft survival were compared with bottom 90% usage centers by using propensity score–matched fine gray regression models. Outcomes were stratified by pre-AC (January 11, 2016 to February 3, 2020) and post-AC (February 4, 2020 to September 30, 2020) eras (Figure). Transplant recipients that cross eras were censored on the last day of the pre-AC era. RESULTS: Included in this study were 2,299 DCD liver transplantation recipients : 2012 in pre-AC and 287 in post-AC eras. High DCD volume (top decile) centers had significantly improved 6-month (hazard ratio 0.32, 95% CI 0.11 to 0.91, p = 0.033) and 1-year (hazard ratio 0.42, 95% CI 0.17 to 0.98, p = 0.043) patient survival in the post-AC era compared with bottom 90% centers by volume. No significant differences were noted in 6-month or 1-year liver graft survival in either era. CONCLUSION: The top decile DCD transplantation volume centers have improved 6-month and 1-year patient survival compared with the lower volume centers with the introduction of the AC policy.Figure

335.3: Comparison of Outcomes of High Utilization Centers For Donation After Circulatory Death Liver Transplantation in the Acuity Circles Era

Introduction: The recent acuity circles (AC) liver allocation policy in the United States has increased rates of donation after circulatory death (DCD) liver transplantation. We hypothesize transplant centers with high volume DCD graft usage may have differing outcomes. Methods: All adult DCD transplant recipients in the UNOS STAR file from Jan 11 2016 to Sept 30 2021 were included. Living liver grafts, pediatric, and non-kidney simultaneous transplantation were excluded. The top decile of DCD transplant centers by volume per year were identified. 6-month and 1-year patient and liver graft survival were compared to bottom 90% usage centers using propensity score matched fine gray regression models. Outcomes were stratified by pre-AC (1/11/2016-2/3/2020) and post-AC (2/4/2020-9/30/2020) eras. Transplant recipients that cross eras were censored on last day of the pre-AC era. Results: 2299 DCD liver transplantation recipients were included in this study, 2012 in pre-AC and 287 in post-AC eras. High DCD volume (top decile) centers had significantly improved 6-month (HR: 0.32, 95% C.I.: 0.11-0.91, P = 0.033) and 1-year (HR: 0.42, 95% C.I.: 0.17-0.98, P = 0.043) patient survival in the post-AC era compared to bottom 90% centers by volume. No significant differences were noted in 6-month or 1-year liver graft survival in either era. Conclusion: The top decile DCD transplantation volume center have improved 6-month and 1-year patient survival compared to lower volume centers with the introduction of the acuity circles policy in the United States.

Normothermic regional perfusion in liver transplantation from donation after cardiocirculatory death: Technical, biochemical, and regulatory aspects and review of literature.

Organs from donation after circulatory death (DCD) are increasingly used for liver transplantation, due to the persisting organ shortage and waiting list mortality. However, the use of DCD grafts is still limited by the inferior graft survival rate and the increased risk of primary non-function and biliary complications when compared to brain death donors' grafts. Abdominal normothermic regional perfusion with extracorporeal membrane oxygenation (ECMO) is an in situ preservation strategy. which may mitigate ischemia-reperfusion injuries. and has been proposed to restore blood perfusion after the determination of death thus optimizing liver function before implantation. In this systematic review, we highlighted the clinical evidence supporting the use of normothermic regional perfusion in DCD liver underlying the pathophysiological mechanisms, and technical, logistic, and regulatory aspects. Despite the lack of properly designed, prospective, randomized trials, the current available data suggest beneficial effects of normothermic regional perfusion on clinical outcomes after liver transplantation.

Decreasing Significance of Early Allograft Dysfunction with Rising Use of Nonconventional Donors.

Background and Objectives: Early allograft dysfunction (EAD) is considered a surrogate marker for adverse post-liver transplant (LT) outcomes. With the increasing use of nonconventional donors, EAD has become a more frequent occurrence. Given this background, we aimed to assess the prevalence and impact of EAD in an updated cohort inclusive of both conventional and nonconventional liver allografts. Materials and Methods: Perioperative and one-year outcomes were assessed for a total of 611 LT recipients with and without EAD from Mayo Clinic Arizona. EAD was defined as the presence of one or more of the following: bilirubin > 10 mg/dL on day 7, INR > 1.6 on day 7, or ALT and/or AST > 2000 IU/L within the first 7 days of LT. Results: Within this cohort, 31.8% of grafts (n = 194) came from donation after circulatory death (DCD) donors, 17.7% (n = 108) were nationally shared, 16.4% (n = 100) were allocated as post-cross clamp, and 8.7% contained moderate steatosis. EAD was observed in 52.2% (n = 321) of grafts in the study cohort (79% in DCD grafts and 40% in DBD grafts). EAD grafts had higher donor risk index (DRI) scores (1.9 vs. 1.6, p < 0.0001), were more likely to come from DCD donors (48% vs. 13.8%, p < 0.0001), were regionally allocated (p = 0.003), and had higher cold ischemia times (median 6.0 vs. 5.5 h, p = 0.001). Primary nonfunction events were rare in both groups (1.3% vs. 0.3%, p = 0.22). Post-LT acute kidney injury occurred at a similar frequency in recipients with and without EAD (43.6% vs. 30.3%, p = 0.41), and there were no differences in ICU (median 2 vs. 1 day, p = 0.60) or hospital (6 vs. 5 days, p = 0.24) length of stay. For DCD grafts, the rate of ischemic cholangiopathy was similar in the two groups (14.9% EAD vs. 17.5% no EAD, p = 0.69). One-year patient survival for grafts with and without EAD was 96.0% and 94.1% (HR 1.2, 95% CI 0.7–1.8; p = 0.54); one-year graft survival was 92.5% and 92.1% (HR 1.0, 95% CI 0.7–1.5; p = 0.88). Conclusions: In this cohort, EAD occurred in 52% of grafts. The occurrence of EAD, however, did not portend inferior outcomes. Compared to those without EAD, recipients with EAD had similar post-operative outcomes, as well as one-year patient and graft survival. EAD should be managed supportively and should not be viewed as a deterrent to utilization of non-ideal grafts.

Post-Kidney Transplantation Results After Circulatory or Brain Death Without Pre-Mortem Heparin Administration.

BackgroundKidney donation after circulatory death (DCD) follows confirmation of death using cardiorespiratory criteria, while donation after brain death (DBD) uses neurological criteria. DBD and DCD donors are the main sources of grafts for transplantation. This retrospective cohort study from a single center in the Czech Republic aimed to compare 5-year post-transplantation outcomes after DCD and DBD transplantation without pre-mortem heparin administration.Material/MethodsA total of 227 recipients with matched donors enrolled in the transplantation program at our institution between 2015 and 2019 were analyzed. Following the application of the inclusion criteria, 99 recipients and 94 matched donors were finally included in the study.ResultsThe duration of cold ischemia (median 961 vs 1100 min, P=0.028) and the perfusion with the preservation solution (median 11 vs 22 min, P<0.001) was statistically significantly shorter in DBD than in DCD grafts. The 1-year survival rates were 97.5% (95% CI 94.1–100.0%) and 90.0% (95% CI: 77.8–100.0%) for DBD and DCD recipients, respectively. The 3-year survival rates were 91.9 (95% CI: 86.0–98.4) and 90.0 (95% CI: 77.8–100.0) for the DBD and DCD groups, respectively. The overall difference in survival between the 2 groups of patients was not statistically significant (P=0.750) nor was disease-free survival (P=0.370).ConclusionsThis retrospective study from a single center showed similar 5-year results after kidney transplantation for DCD and DBD donors without pre-mortem heparin administration, including the time to graft failure and patient survival.

Disparities in the Use of Older Donation After Circulatory Death Liver Allografts in the United States Versus the United Kingdom.

This study aimed to assess the differences between the United States and the United Kingdom in the characteristics and posttransplant survival of patients who received donation after circulatory death (DCD) liver allografts from donors aged >60 y. Data were collected from the UK Transplant Registry and the United Network for Organ Sharing databases. Cohorts were dichotomized into donor age subgroups (donor >60 y [D >60]; donor ≤60 y [D ≤60]). Study period: January 1, 2001, to December 31, 2015. 1157 DCD LTs were performed in the United Kingdom versus 3394 in the United States. Only 13.8% of US DCD donors were aged >50 y, contrary to 44.3% in the United Kingdom. D >60 were 22.6% in the United Kingdom versus 2.4% in the United States. In the United Kingdom, 64.2% of D >60 clustered in 2 metropolitan centers. In the United States, there was marked inter-regional variation. A total of 78.3% of the US DCD allografts were used locally. One- and 5-y unadjusted DCD graft survival was higher in the United Kingdom versus the United States (87.3% versus 81.4%, and 78.0% versus 71.3%, respectively; P < 0.001). One- and 5-y D >60 graft survival was higher in the United Kingdom (87.3% versus 68.1%, and 77.9% versus 51.4%, United Kingdom versus United States, respectively; P < 0.001). In both groups, grafts from donors ≤30 y had the best survival. Survival was similar for donors aged 41 to 50 versus 51 to 60 in both cohorts. Compared with the United Kingdom, older DCD LT utilization remained low in the United States, with worse D >60 survival. Nonetheless, present data indicate similar survivals for older donors aged ≤60, supporting an extension to the current US DCD age cutoff.

Donation after Circulatory Death Liver Transplantation in Paediatric Recipients

Waiting list mortality together, with limited availability of organs, are one of the major challenges in liver transplantation (LT). Especially in the paediatric population, another limiting factor is the scarcity of transplantable liver grafts due to additional concerns regarding graft size matching. In adults, donation after circulatory death (DCD) liver grafts have been used to expand the donor pool with satisfactory results. Although several studies suggest that DCD livers could also be used in paediatric recipients with good outcomes, their utilisation in children is still limited to a small number of reports. Novel organ perfusion strategies could be used to improve organ quality and help to increase the number of DCD grafts utilised for children. With the current manuscript, we present the available literature of LT using DCD grafts in paediatric recipients, discussing current challenges with the use of these livers in children and how machine perfusion technologies could be of impact in the future.