Circulatory Death Donors Research Articles

Machine Perfusion or Straight to Transplant? Predictive Value of Flavin Mononucleotide Levels in Flush Solution of Human Liver Allograft.

This study examined the predictive value of Flavin Mononucleotide (FMN) levels in the flush solution used during cold storage of donor livers on outcomes post-transplantation. Static cold storage for liver grafts induces hypoxia with subsequent impaired mitochondrial function and Flavin Mononucleotide (FMN) release upon reperfusion. This study enrolled 62 recipients who received whole liver grafts from donation after brain death (n=50) and circulatory death donors (n=12) between June 2022 and July 2023. FMN concentrations were measured in flush solutions on the back-table. ROC-curve analysis identified an FMN level cut-off for graft survival. Post-transplant outcomes were examined according to FMN levels. FMN level was significantly associated with graft survival, with an area-under-the-curve (AUC) of 0.858 (95%CI: 0.754-0.963, P<0.001), outperforming the donor risk index (AUC 0.571, 95%CI: 0.227-0.915, P=0.686). The study cohort was divided into low-FMN (<37.5ng/mL, n=40) and high-FMN groups (≥37.5ng/mL, n=22). The low-FMN group had superior one-year graft survival compared with the high-FMN group (100% vs. 77%, P=0.003). Levels of transaminases within 7 days post-transplant were significantly higher in the high-FMN group (P=0.003). The high-FMN group developed acute rejections (41% vs. 15%, P=0.023) and early allograft dysfunction (50% vs. 20%, P=0.014) more frequently. Median comprehensive complication index in the high-FMN group was significantly higher (54 [interquartile range, 40-78] vs. 42 [interquartile range, 28-52], P=0.017). The FMN level measured in donor livers' cold storage flush solution is a valid biomarker to predict post-transplant outcomes. Liver grafts with high FMN levels may benefit from machine perfusion to improve outcomes.

Using an Isolated Working Rat Heart Model to Test Donor Heart Preservation Strategies.

Optimization of donor heart preservation solutions has played a key role in reducing ischemia-reperfusion injury in donor hearts during organ retrieval, transportation, and transplantation. Previous work from our laboratory showed that the addition of glyceryl trinitrate and erythropoietin to donor heart preservation solutions could significantly improve cardiac functional recovery after prolonged cold storage and in donation after circulatory death hearts. This supplementation protocol has been implemented in clinical use in transplant units around Australia, Belgium, and the United Kingdom. Here, we outline a protocol for testing supplementation strategies using an ex vivo isolated working rat heart (IWRH) perfusion circuit. Using this methodology, supplementation strategies can be tested in the context of prolonged cold static storage, donation after brain death, and donation after circulatory death donor heart preservation. Cardiac functional recovery, measured by aortic flow, coronary flow, cardiac output, pulse pressure, and heart rate, can be used to determine whether a particular preservation strategy can minimize ischemia-reperfusion injury of the donor heart.

Loss of Nr4a1 ameliorates endothelial cell injury and vascular leakage in lung transplantation from circulatory-death donor

BackgroundIschemia-reperfusion injury (IRI) stands as a major trigger for primary graft dysfunction (PGD) in lung transplantation (LTx). Especially in LTx from donation after cardiac death (DCD), effective control of IRI following warm ischemia (WIRI) is crucial to prevent PGD. This study aimed to identify the key factors affecting WIRI in LTx from DCD. MethodsPreviously reported RNA-sequencing dataset of lung WIRI was reanalyzed to identify nuclear receptor subfamily 4 group A member 1 (NR4A1) as the immediate early gene for WIRI. Dynamics of NR4A1 expression were verified using a mouse hilar clamp model. To investigate the role of NR4A1 in WIRI, a mouse model of LTx from DCD was established using Nr4a1 knockout (Nr4a1-/-) mice. ResultsNR4A1 was located around vascular cells, and its protein levels in the lungs increased rapidly and transiently during WIRI. LTｘ from Nr4a1-/- donors significantly improved pulmonary graft function compared to wild-type donors (P < 0.001). Histological analysis showed decreased microvascular endothelial cell death (P = 0.007), neutrophil infiltration (P < 0.001), and albumin leakage (P < 0.001). Evans blue permeability assay demonstrated maintained pulmonary microvascular barrier integrity in grafts from Nr4a1-/- donors, correlating with diminished pulmonary edema (P < 0.001). However, NR4A1 did not significantly affect the inflammatory response during WIRI, and IRI was not suppressed when a wild-type donor lung was transplanted into the Nr4a1-/- recipient. ConclusionsDonor NR4A1 plays a specialized role in the positive regulation of endothelial cell injury and microvascular hyperpermeability. These findings demonstrate the potential of targeting NR4A1 interventions to alleviate PGD and improve outcomes in LTx from DCD.

Delayed Graft Function Equally Worsens Early Outcomes in Kidney Recipients from Donation after Circulatory Death vs. Brain Death Donors

Delayed Graft Function Equally Worsens Early Outcomes in Kidney Recipients from Donation after Circulatory Death vs. Brain Death Donors

Innovations in Liver Preservation Techniques for Transplants from Donors after Circulatory Death: A Special Focus on Transplant Oncology.

Liver transplantation is the preferred treatment for end-stage liver disease. Emerging evidence suggests a potential role for liver transplantation in treating liver tumors such as colorectal liver metastases and cholangiocarcinoma. However, due to a limited donor pool, the use of marginal grafts from donation after circulatory death (DCD) donors is increasing to meet demand. Machine perfusion is crucial in this context for improving graft acceptance rates and reducing ischemia-reperfusion injury. Few studies have evaluated the role of machine perfusion in the context of transplant oncology. Perfusion machines can be utilized in situ (normothermic regional perfusion-NRP) or ex situ (hypothermic and normothermic machine perfusion), either in combination or as a complement to conventional in situ cold flush and static cold storage. The objective of this analysis is to provide an up-to-date overview of perfusion machines and their function in donation after circulatory death with particular attention to their current and likely potential effects on transplant oncology. A literature review comparing standard cold storage to machine perfusion methods showed that, so far, there is no evidence that these devices can reduce the tumor recurrence rate. However, some evidence suggests that these innovative perfusion techniques can improve graft function, reduce ischemia-reperfusion injury, and, based on this mechanism, may lead to future improvements in cancer recurrence.

Islet-after-kidney transplantation versus kidney alone in kidney transplant recipients with type 1 diabetes (KAIAK): a population-based target trial emulation in France

Islet transplantation has been associated with better metabolic control and quality of life than insulin treatment alone, but direct evidence of its effect on hard clinical endpoints is scarce. We aimed to assess the effect of islet transplantation on patient-graft survival in kidney transplant recipients with type 1 diabetes. In this retrospective cohort study, we enrolled all patients with type 1 diabetes who received a kidney graft in France during the study period, identified from the CRISTAL nationwide registry. Non-inclusion criteria included recipients from transplant centres that never proposed islet transplantation during the study period, recipients with a functional pancreas throughout the follow-up duration, recipients with more than two kidney transplants, HLA-sensitised recipients, recipients with less than 1 year of follow-up after kidney transplantation, misclassified recipients with type 2 diabetes, recipients aged over 65 years, recipients of kidney grafts from Donation after Circulatory Death donors, recipient with HIV or hepatitis, recipients with cancer, and recipients of combined liver-kidney transplants. Patients who also received islet-after-kidney (IAK) transplantation were compared with controls who received kidney transplantation alone according to a 1:2 matching method based on time-dependent propensity scores, ensuring patients comparability at the time of islet transplantation. The primary outcome was patient-graft survival, a composite outcome defined by death, re-transplantation, or return to dialysis. Between Jan 1, 2000, and Dec 31, 2017, 2391 patients with type 1 diabetes were identified as having received a kidney transplant, 47 patients of whom also received an islet transplantation. 2002 patients were not eligible for islet transplantation and 62 were excluded due to missing data. 327 eligible recipients from 15 centres were included in the study dataset for the target trial emulation. 40 patients who received IAK transplantation were successfully matched to 80 patients who received kidney transplantation alone. 13 (33%) of 40 patients in the IAK transplantation group returned to dialysis or died, compared with 36 (45%) of 80 patients in the kidney transplantation alone group. We found a significant benefit of islet transplantation compared with kidney transplantation alone on patient-graft survival, with a hazard ratio (HR) of 0·44 (95% CI 0·23-0·88; p=0·022), mainly explained by a protective effect on the risk of death (HR 0·41, 0·13-0·91; p=0·042). There was no meaningful association between IAK and death-censored graft survival (0·73, 0·30-1·89; p=0·36). In kidney transplant recipients with type 1 diabetes, IAK transplantation was associated with a significantly better patient-graft survival compared with kidney transplantation alone, mainly due to a protective effect on the risk of death. These results potentially serve as compelling grounds for advocating wider access to islet transplantation in patients with type 1 diabetes undergoing kidney transplant, as reimbursement of islet transplantation is provided in few countries worldwide. Programme Hospitalier de la Recherche Clinique, Fondation pour la Recherche Medicale, and Fonds de Dotation Line Renaud-Loulou Gasté.

Early outcomes in heart transplantation using donation after circulatory death donors in patients bridged with durable left ventricular assist devices

ObjectiveDonation after circulatory death heart transplantation potentially increases donor allografts, especially for patients with lower listing status. We assessed the outcomes of donation after circulatory death heart transplantation in patients bridged with durable left ventricular assist devices. MethodsThe United Network for Organ Sharing database was queried for adult heart transplants using donation after circulatory death donors from 2019 to 2022. Patients were stratified between those with durable left ventricular assist devices and those with intra-aortic balloon pump, inotropic, or no bridging support (control group). Primary outcome was 1-year mortality. Secondary end points were hospital length of stay, stroke, pacemaker implantation, dialysis, and acute rejection before discharge. ResultsA total of 160 left ventricular assist device recipients and 311 control recipients met study inclusion criteria. Recipients bridged with left ventricular assist devices were younger (55 vs 58 years, P < .001) with lower body mass index (28.3 vs 30.3, P < .001), longer waitlist times (112 vs 34 days, P < .001), longer out of body times (5.7 vs 4.6 hours, P < .001), and less frequent normothermic regional perfusion (31% vs 40%, P = .049). Patients with left ventricular assist devices commonly underwent transplantation at United Network for Organ Sharing status 3 and 4 (92%), whereas control patients underwent transplantation at status 2 (27%), status 3 (10%), status 4 (30%), or status 6 (30%). Kaplan–Meier analysis showed no difference in 1-year mortality between groups (P = .34). However, acute rejection was higher in the unadjusted left ventricular assist device cohort (26% vs 13%, P < .001). On multivariable logistic regression, left ventricular assist device was an independent predictor of acute rejection (odds ratio, 2.21, 95% CI, 1.32-3.69, P = .002). ConclusionsDurable left ventricular assist devices may be associated with a higher risk of developing an early inflammatory response in donation after circulatory death heart transplantation; however, 1-year survival was similar between groups.

The current landscape of in situ and ex situ machine perfusion utilization for liver grafts from cardiac donation after circulatory death donors in the US

Donation after circulatory death (DCD) is driving the increase in deceased organ donors in the United States. Normothermic regional perfusion (NRP) and ex situ machine perfusion (es-MP) have been instrumental in improving liver transplant outcomes and graft utilization. This study examines the current landscape of liver utilization from cardiac DCD donors in the United States. Using the United Network for Organ Sharing Standard Transplant Analysis and Research file, all adult (≥18 years old) DCD donors in the United States from which the heart was used for transplantation from October 1, 2020, to September 30, 2023, were compared by procurement technique (NRP versus super rapid recovery [SRR]) and storage strategy (es-MP versus static cold storage). One hundred eighty-eight livers were transplanted from 309 thoracoabdominal NRP donors (61% utilization) versus 305 (56%) liver transplants from 544 SRR donors. es-MP was used in 20% (n = 38) of NRP cases versus 32% (98) of SRR cases. Of the liver grafts, 281 (59%) were exposed to NRP, es-MP, or both. While there is widespread utilization of machine perfusion, more research is needed to determine optimal graft management strategies, particularly concerning the use of multiple technologies in complementary ways. More complete data collection is necessary at a national level to address these important research questions.

Myocardial oxygen handling and metabolic function of ex-situ perfused human hearts from circulatory death donors

BackgroundThis study investigated oxygen handling of human hearts donated after circulatory death (DCD) on normothermic ex-situ heart perfusion (ESHP) and evaluated oxygen handling markers as adjuncts to cardiac viability assessment. MethodsThis single-center retrospective study included human DCD heart transplantation procedures using ESHP. Lactate concentrations, blood gas, myocardial oxygen consumption (MVO2), delivery (MDO2) and extraction (MEO2), coronary blood flow (CBF), coronary vascular resistance (CVR), and adenosine infusion were reported over time. Correlation between parameters was assessed, and statistical testing compared patients who did and did not require extracorporeal membrane oxygenation (ECMO) support after transplantation. ResultsLactate concentrations decreased during ESHP in all transplanted hearts (n=25) and increased in 1 rejected heart. Arterial PO2 was 75.2±2.9 kPa, with an arteriovenous ΔPO2 of 44.8±10.4 kPa. Oxygen saturation was 100% in most arterial and venous samples. Average MVO2 was 2.7±0.6 mL·min-1·100·g-1 myocardium, MDO2 98.5±20.4 mL·min-1, and MEO2 8.6±1.8%. Average CVR was 0.025±0.006 mmHg∙min∙mL-1∙100 g-1 and increased over time. ΔPO2 correlated strongly with MVO2 (R=0.797, p<0.001) and lactate trend (R=0.799, p<0.001) in transplanted hearts, without differences compared to the rejected heart with increasing lactate. Adenosine infusion on ESHP was significantly higher in patients requiring ECMO post-transplantation versus non-ECMO cases (11.7 (4.5-21.0) vs. 2.2 (1.5-6.7) mL·h-1, p=0.039). ConclusionsHearts on normothermic ESHP receive excessive MDO2, due to high PO2 and CBF, while the MVO2 is relatively low. Thus, CBF and PO2 can potentially be lowered. Furthermore, ΔPO2 could serve as additional marker of metabolic function under these hyperoxic circumstances. The adenosine infusion rate might predict post-transplantation ECMO requirement.

Diagnosing the Recent Decrease in Utilization of Deceased Donor Kidneys.

The number of deceased donor kidney transplants has been increasing and is at a record high, yet nonuse of kidneys recovered for transplantation has risen to 25.8% following circular kidney allocation system based on 250-nautical-mile circles implemented on March 15, 2021 (KAS250). Using Scientific Registry of Transplant Recipients data, we studied all deceased donor kidneys recovered for transplant from March 15, 2019, to January 31, 2023. We calculated the association of multiple factors with kidney nonuse, including increasing recovery of kidneys from nonideal donors, delays in offer acceptance observed under KAS250, and impacts of COVID-19. In the 2 y before KAS250, the nonuse rate was 21.2%. Had this rate continued, 2334 more kidneys would have been transplanted through January 2023. We estimated that about 769 of these nonused kidneys (33%) were associated with offer acceptance delays under KAS250; about 994 of these nonused kidneys (43%) were associated with increased prevalence of nonideal donors: donation after circulatory death donors, older donors, and donors with elevated peak serum creatinine; and about 542 of these nonused kidneys (23%) were associated with an otherwise unexplained gradual upward trend in nonuse of recovered kidneys across the pre-KAS250 and KAS250 eras. The overall impact of COVID-19 on the nonuse rate was not significant. The rise in kidney nonuse rate was significantly associated with both increased recovery of nonideal donors, and with KAS250 allocation complexity and delays. Increasing recovery of kidneys from nonideal donors benefits patients because recovering more kidneys increases the number of kidneys available for transplant.

Expanding Horizons in Cardiac Transplant: Efficacy and Outcomes of Circulatory and Brain Death Donor Hearts in a Newly Implemented Cardiac Transplant Program with Limited Donor Accessibility and a Literature Review.

(1) Background: Cardiac donation after circulatory death (DCD) is an emerging paradigm in organ transplantation. However, this technique is recent and has only been implemented by highly experienced centers. This study compares the characteristics and outcomes of thoraco-abdominal normothermic regional perfusion (TANRP) and static cold-storage DCD and traditional donation after brain death (DBD) cardiac transplants (CT) in a newly stablished transplant program with restricted donor availability. (2) Method: We performed a retrospective, single-center study of all adult patients who underwent a CT between November 2019 and December 2023, with a follow-up conducted until August 2024. Data were retrieved from medical records. A review of the current literature on DCD CT was conducted to provide a broader context for our findings. The primary outcome was survival at 6 months after transplantation. (3) Results: During the study period, 76 adults (median age 56 years [IQR: 50-63 years]) underwent CT, and 12 (16%) were DCD donors. DCD donors had a similar age (46 vs. 47 years, p = 0.727), were mostly male (92%), and one patient had left ventricular dysfunction during the intraoperative DCD process. There were no significant differences in recipients' characteristics. Survival was similar in the DCD group compared to DBD at 6 months (100 vs. 94%) and 12 months post-CT survival (92% vs. 94%), p = 0.82. There was no primary graft dysfunction in the DCD group (9% in DBD, p = 0.581). The median total hospital stay was longer in the DCD group (46 vs. 21 days, p = 0.021). An increase of 150% in transplantation activity due to DCD was estimated. (4) Conclusions: In a new CT program that utilized older donors and included recipients with similar illnesses and comorbidities, comparable outcomes between DCD and DBD hearts were observed. DCD was rapidly incorporated into the transplant activity, demonstrating an expedited learning curve and significantly increasing the availability of donor hearts.

Extended ischemic times during exvivo lung perfusion is not associated with increased mortality.

The purpose of this study was to identify the association of increasing ischemic times in recipients who receive lungs evaluated by exvivo lung perfusion (EVLP) and their association with outcomes following lung transplantation. Lung transplant recipients who received an allograft evaluated by EVLP were identified from the United Network for Organ Sharing (UNOS) Database from 2016-2023. Recipients were stratified into three groups based on total ischemic time (TOT): short TOT (STOT, 0 to <7 h), medium TOT (MTOT, 7> to <14 h), and long TOT (LTOT, +14 h). The groups were assessed with comparative statistics and Kaplan-Meier methods. A Cox regression was created to determine the association of ischemic time in EVLP donors and long-term mortality. Recipients in the LTOT group had significantly longer length of stay and post-operative extracorporeal membrane use at 72 h (p < 0.05 for both). Additionally, they had nonsignificant increases in rate of stroke (4.7%, p = 0.05) and primary graft dysfunction grade 3 (PGD3, 27.5%, p = 0.082). However, there was no significant difference in hospital mortality or mid-term survival (p > 0.05 for both). On multivariable analysis, ischemic time was not associated with increased mortality whereas increasing recipient age, preoperative ECMO use and donation after circulatory death donors were (p < 0.05 for all). If EVLP technology is available, under certain circumstances, surgeons should not be dissuaded from using an allograft with extended ischemic time.

Increasing Multiorgan Heart Transplantations From Donation After Circulatory Death Donors in the United States.

Donation after circulatory death (DCD) donors are becoming an important source of organs for heart-transplantation (HT), but there are limited data regarding their use in multiorgan-HT. Between January 2020 and June 2023, we identified 87 adult multiorgan-HTs performed using DCD-donors [77 heart-kidney, 6 heart-lung, 4 heart-liver] and 1494 multiorgan-HTs using donation after brain death (DBD) donors (1141 heart-kidney, 165 heart-lung, 188 heart-liver) in UNOS. For heart-kidney transplantations (the most common multiorgan-HT combination from DCD-donors), we also compared donor/recipient characteristics, and early outcomes, including 6-month mortality using Kaplan-Meier (KM) and Cox hazards-ratio (Cox-HR). Use of DCD-donors for multiorgan-HTs in the United States increased from 1% in January to June 2020 to 12% in January-June 2023 (p < 0.001); but there was a wide variation across UNOS regions and center volumes. Compared to recipients of DBD heart-kidney transplantations, recipients of DCD heart-kidney transplantations were less likely to be of UNOS Status 1/2 at transplant (35.06%vs. 69.59%) and had lower inotrope use (22.08%vs. 43.30%), lower IABP use (2.60%vs. 26.29%), but higher durable CF-LVAD use (19.48%vs. 12.97%), all p < 0.01. Compared to DBD-donors, DCD-donors used for heart-kidney transplantations were younger [28(22-34) vs. 32(25-39) years, p=0.004]. Recipients of heart-kidney transplantations from DCD-donors and DBD-donors had similar 6-month survival using both KM analysis, and unadjusted and adjusted Cox-HR models, including in propensity matched cohorts. Rates of PGF and in-hospital outcomes were also similar. Use of DCD-donors for multiorgan-HTs has increased rapidly in the United States and early outcomes of DCD heart-kidney transplantations are promising.

Donation After Circulatory Death Cardiac Recovery Technique: Single-Center Observational Outcomes

BackgroundRecovery of hearts from donation after circulatory death donors has been performed either with direct procurement and perfusion (DPP) using the TransMedics Organ Care System or with normothermic regional perfusion (NRP) with subsequent cold storage. It remains unclear which of these 2 strategies yields optimal posttransplant outcomes. MethodsAll heart transplant recipients from donors after circulatory death donors at the Vanderbilt University Medical Center (Nashville, TN) were reviewed (February 2020 to January 2023). Recipients were stratified into an NRP or DPP cohort. All DPP recoveries were performed using the TransMedics Organ Care System. The key outcome was severe primary graft dysfunction at 24 hours, defined by the need for postoperative extracorporeal membrane oxygenation. ResultsA total of 118 hearts were transplanted (NRP, 87; DPP, 31). Donors recovered using NRP were younger (25 years [interquartile range {IQR}, 21-31 years] vs 31 years [IQR, 24-37 years]; P = .008) and had shorter distance traveled (292 miles [158-516 miles] vs 449 miles [IQR, 248-635 miles]; P = .02). Recipient preoperative risk factors were similar between the groups. There was no difference in the incidence of severe primary graft dysfunction at 24 hours (NRP, 5.8%; and DPP, 12.9%; P = .24). However, ejection fraction at 7 days after transplantation was higher in the NRP group (65% [IQR, 60%-65%] vs 60% [IQR, 60%-68%]; P = .005). There was no difference in inotrope scores at 24 hours (P = 1.00) or 72 hours (P = .87) or in 30-day (NRP, 95% vs DPP, 97%; P = .75) and 1-year (NRP, 94% vs DPP, 86%; P = .19) survival. ConclusionsNRP and DPP strategies for recovery of cardiac allografts yield comparable early allograft outcomes. Future studies are needed to confirm these findings in larger prospective cohorts.

Centralized Static Ex-Vivo Lung Perfusion in the United States

Ex-vivo lung perfusion (EVLP) may improve donor lung utilization but requires significant infrastructure and expertise. Centralized EVLP facilities may mitigate these requirements. From the United Network for Organ Sharing database, we identified 345 adults undergoing isolated, first-time lung transplantation using donor lungs perfused by static EVLP (03/01/2018-12/31/2022). Recipients of lungs perfused at centralized EVLP facilities (n=165) were compared to recipients of lungs perfused at individual transplant centers (n=180). Propensity score matching was used to create balanced groups for comparison. Centralized EVLP facilities were increasingly utilized from 2018 to 2022 (35.3 vs. 55.8%, p=0.04) and were more likely used when the annual center volume of EVLP lung transplants was low. Compared to allografts placed on EVLP at individual transplant centers, those placed on EVLP at centralized facilities had longer median ischemic time (11.3 vs. 9.6 hours, p<0.001) and were less likely to come from donation after circulatory death donors (25.4 vs. 39.5%, p=0.003) or be used for double lung transplant (73.3 vs. 83.9%, p=0.02). In 102 well-matched recipients, 2-year survival was equivalent between those receiving allografts perfused at centralized facilities (77.9% [95% CI 68.0-85.1%]) versus individual transplant centers (77.7% [95% CI 67.8-84.9%], p=0.90). Multivariable Cox regression analysis also showed equivalent 2-year survival (adjusted hazard ratio 1.02, 95% CI 0.57-1.84, p=0.95). Transplanting lung allografts that underwent static EVLP at centralized facilities had similar outcomes compared to transplanting lungs perfused at individual transplant centers. The centralized model of clinical EVLP can potentially improve access to EVLP.

Consensus Statement: Technical Standards for Thoracoabdominal Normothermic Regional Perfusion

BackgroundThoracoabdominal normothermic regional perfusion (TA-NRP) has emerged as a powerful technique for optimizing organ procurement from donation after circulatory death donors. Despite its rapid adoption, standardized guidelines for TA-NRP implementation are lacking, prompting the need for consensus recommendations to ensure safe and effective utilization of this technique. MethodsA working group composed of members from The American Society of Transplant Surgeons, The International Society of Heart and Lung Transplantation, The Society of Thoracic Surgeons, and The American Association for Thoracic Surgery was convened to develop technical guidelines for TA-NRP. The group systematically reviewed existing literature, consensus statements, and expert opinions to identify key areas requiring standardization, including predonation evaluation, intraoperative management, postdonation procedures, and future research directions. ResultsThe working group formulated recommendations encompassing donor evaluation and selection criteria, premortem testing and therapeutic interventions, communication protocols, and procedural guidelines for TA-NRP implementation. These recommendations aim to facilitate coordination among transplant teams, minimize variability in practice, and promote transparency and accountability throughout the TA-NRP process. ConclusionsThe consensus guidelines presented herein serve as a comprehensive framework for the successful and ethical implementation of TA-NRP programs in organ procurement from donation after circulatory death donors. By providing standardized recommendations and addressing areas of uncertainty, these guidelines aim to enhance the quality, safety, and efficiency of TA-NRP procedures, ultimately contributing to improved outcomes for transplant recipients.

Consensus Statement: Technical Standards for Thoracoabdominal Normothermic Regional Perfusion.

Thoracoabdominal normothermic regional perfusion (TA-NRP) has emerged as a powerful technique for optimizing organ procurement from donation after circulatory death donors. Despite its rapid adoption, standardized guidelines for TA-NRP implementation are lacking, prompting the need for consensus recommendations to ensure safe and effective utilization of this technique. A working group composed of members from The American Society of Transplant Surgeons, The International Society of Heart and Lung Transplantation, The Society of Thoracic Surgeons, and The American Association for Thoracic Surgery was convened to develop technical guidelines for TA-NRP. The group systematically reviewed existing literature, consensus statements, and expert opinions to identify key areas requiring standardization, including predonation evaluation, intraoperative management, postdonation procedures, and future research directions. The working group formulated recommendations encompassing donor evaluation and selection criteria, premortem testing and therapeutic interventions, communication protocols, and procedural guidelines for TA-NRP implementation. These recommendations aim to facilitate coordination among transplant teams, minimize variability in practice, and promote transparency and accountability throughout the TA-NRP process. The consensus guidelines presented herein serve as a comprehensive framework for the successful and ethical implementation of TA-NRP programs in organ procurement from donation after circulatory death donors. By providing standardized recommendations and addressing areas of uncertainty, these guidelines aim to enhance the quality, safety, and efficiency of TA-NRP procedures, ultimately contributing to improved outcomes for transplant recipients.

Recent solid-phase microextraction-based analytical approaches for the profiling of biliary bile acids in pre-transplant assessments of liver grafts subjected to normothermic ex vivo liver perfusion

BackgroundLiver transplantation is the definitive treatment for end-stage liver failure, but the scarcity of donor organs remains a significant challenge. Leveraging organs from extended criteria donors (ECD) offers a potential avenue to address worldwide shortages, though these organs are more susceptible to post-reperfusion injury. This study explores the use of normothermic ex vivo liver perfusion (NEVLP) as a method for organ preservation – an approach that sustains liver metabolism and facilitates pre-transplant assessments of organ viability via bile analysis. The focal point of this study revolves on the development of analytical methods for determining the bile acid profile throughout the peritransplantation period as a potential indicator of liver function and viability. ResultsThe study optimized and validated a high-throughput analytical method to quantify selected bile acids in bile samples using a thin-film microextraction-liquid chromatography-mass spectrometry (TFME-LC-MS) platform. Furthermore, it introduced a solid-phase microextraction-microfluidic open interface-mass spectrometry (SPME-MOI-MS) method for rapid direct analysis of bile acid isobar groups. In the animal study, discernible variations in the concentrations of specific bile acids were observed between donors after circulatory death (DCD) and heart-beating donors (HBD), particularly following normothermic perfusion and reperfusion. Noteworthy fluctuations in individual bile acid concentrations were observed throughout the entire organ transplantation process, with taurocholic acid (TCA), glycocholic acid (GCA), and glycochenodeoxycholic acid (GCDCA) emerging as promising indicators of organ quality. The efficacy of the SPME-MOI-MS platform in corroborating these trends highlights its potential for real-time bile acid analysis during liver transplantation procedures. SignificanceOur findings underscore the efficacy of NEVLP in tandem with advanced bile acid analysis methods as a reliable strategy for pre-transplant assessments of organ viability, potentially increasing the use of ECD organs and reducing organ shortages. The ability to monitor bile acid profiles in real-time provides crucial insights into liver function and ischemic injury, making significant strides in improving transplant outcomes and patient survival rates.

Impact of dual thoracic recovery from circulatory death donors on heart and lung transplant outcomes

ObjectivesConcomitant heart and lung recovery can result in increased operative complexity, ischemic time, and competition for resources and anatomic territory. Dual thoracic recovery from circulatory death donors may have additional risks that are not fully understood. We investigated the effects of dual heart and lung recovery from circulatory death donors on thoracic transplant outcomes. MethodsUsing the United Network for Organ Sharing database, we categorized all adult thoracic circulatory death donor transplants from 2019 to 2023 by whether the donor heart, lung, or both (dual donors) were recovered. Heart and lung transplant outcomes were compared between dual recovery donors and heart-only or lung-only donors, respectively, using multivariable analyses. ResultsOf the 2513 donors included, 42.9% were heart-only, 45.0% were lung-only, and 12.0% were dual donors. Recipients of dual versus heart-only donors had similar likelihood of post-transplant dialysis (18.9% vs 18.3%, P = .84), likelihood of stroke (2.9% vs 4.7%, P = .34), and 2-year risk of mortality (adjusted hazard ratio, 1.15 [95% CI, 0.90-1.47], P = .26), but lower likelihood of acute rejection (10.2% vs 16.1%, P = .04). Recipients of dual and lung-only donors had similar likelihood of predischarge acute rejection (7.6% vs 8.5%, P = .70), intubation at 72 hours (38.9% vs 45.1%, P = .13), and extracorporeal membrane oxygenation at 72 hours (13.1% vs 18.1%, P = .11), as well as 2-year risk of mortality (adjusted hazard ratio, 1.16 [95% CI, 0.74-1.82], P = .52). ConclusionsRecovering both the heart and lungs from a circulatory death donor does not negatively impact transplant outcomes. Outcomes in this population should continue to be investigated as more data and longer-term follow-up become available.

Prophylactic Anticoagulation Reduces the Risk of Kidney Graft Venous Thrombosis in Recipients From Uncontrolled Donation After Circulatory Death Donors With High Renal Resistive Index.

Uncontrolled donation after circulatory death (uDCD) increases organ availability for kidney transplantation (KT) at the expense of a higher risk of primary graft nonfunction (PNF). At least half of the cases of PNF are secondary to graft venous thrombosis. The potential benefit from prophylactic anticoagulation in this scenario remains unclear. In this single-center retrospective study we compared 2 consecutive cohorts of KT from uDCD with increased (≥0.8) renal resistive index (RRI) in the Doppler ultrasound examination performed within the first 24-72 h after transplantation: 36 patients did not receive anticoagulation ("nonanticoagulation group") and 71 patients underwent prophylactic anticoagulation until normalization of RRI in follow-up Doppler examinations ("anticoagulation group"). Anticoagulation was initiated at a median of 2 d (interquartile range, 2-3) after transplantation and maintained for a median of 12 d (interquartile range, 7-18). In 4 patients (5.6%), anticoagulation had to be prematurely stopped because of the development of a hemorrhagic complication. In comparison with the nonanticoagulation group, recipients in the anticoagulation group had a lower 2-wk cumulative incidence of graft venous thrombosis (19.4% versus 0.0%; P < 0.001) and PNF (19.4% versus 2.8%; P = 0.006). The competing risk analysis with nonthrombotic causes of PNF as the competitive event confirmed the higher risk of graft thrombosis in the nonanticoagulation group (P = 0.0001). The anticoagulation group had a higher incidence of macroscopic hematuria (21.1% versus 5.6%; P = 0.049) and blood transfusion requirements (39.4% versus 19.4%; P = 0.050) compared with the nonanticoagulation group. No graft losses or deaths were attributable to complications potentially associated with anticoagulation. Early initiation of prophylactic anticoagulation in selected KT recipients from uDCD with an early Doppler ultrasound RRI of ≥0.8 within the first 24-72 h may reduce the incidence of graft venous thrombosis as a cause of PNF.