Allocation Of Donor Organs Research Articles

Improving long-term kidney allograft survival by rethinking HLA compatibility: from molecular matching to non-HLA genes.

Optimizing immunologic compatibility in organ transplantation extends beyond the conventional approach of Human Leukocyte Antigen (HLA) antigen matching, which exhibits significant limitations. A broader comprehension of the roles of classical and non-classical HLA genes in transplantation is imperative for enhancing long-term graft survival. High-resolution molecular HLA genotyping, despite its inherent challenges, has emerged as the cornerstone for precise patient-donor compatibility assessment. Leveraging understanding of eplet biology and indirect immune activation, eplet mismatch calculators and the PIRCHE-II algorithm surpass traditional methods in predicting allograft rejection. Understanding minor histocompatibility antigens may also present an opportunity to personalize the compatibility process. While the application of molecular matching in deceased donor organ allocation presents multiple technical, logistical, and conceptual barriers, rendering it premature for mainstream use, several other areas of donor-recipient matching and post-transplant management are ready to incorporate molecular matching. Provision of molecular mismatch scores to physicians during potential organ offer evaluations could potentially amplify long-term outcomes. The implementation of molecular matching in living organ donation and kidney paired exchange programs is similarly viable. This article will explore the current understanding of immunologic matching in transplantation and the potential applications of epitope and non-epitope molecular biology and genetics in clinical transplantation.

Surveillance for donor‐derived infections in Australia

AbstractBackgroundSystems for quality and safety assurance in organ donation and transplantation are vital, especially those that seek to minimize donor disease transmission. Australia has developed a national vigilance and surveillance system to identify, review, and analyze actual and potential donor‐derived infections and other disease transmissions.MethodsThe system involves notification of incidents to the Australian Organ and Tissue Authority for review by a Vigilance and Surveillance Expert Advisory Committee (VSEAC). The VSEAC grades incidents, O makes recommendations, and issues communications both publicly and to the clinical donation and transplant sector.ResultsAnnual notifications have increased since the inception of the system in 2012 until 2022. The vast majority relate to procedural aspects including donor assessment, information/data issues, and the recovery, offer, allocation, preservation and transportation of organs. Possible donor‐derived disease accounted for 19% of all notifications, and those related to possible donor‐derived infection only 12%. The VSEAC, as a result of reviewing these incidents, has made recommendations resulting in revisions to donor screening, organ allocation, packaging and transportation. The review of incidents has led to changes in clinical guidance for increased viral risk donor assessment, testing, and ensuing organ utilization and recipient surveillance. Guidance has also been reviewed for other infectious risks including strongyloides, human T‐lymphotropic virus, and HEV.ConclusionThe Australian vigilance and surveillance system has enabled national retrospective reporting and evaluation of serious adverse events or reactions to identify trends and inform processes and guidelines, therefore improving the safety of donation and transplantation. image

The role of coronary artery disease in lung transplantation: a propensity-matched analysis.

Candidate selection for lung transplantation (LuTx) is pivotal to ensure individual patient benefit as well as optimal donor organ allocation. The impact of coronary artery disease (CAD) on post-transplant outcomes remains controversial. We provide comprehensive data on the relevance of CAD for short- and long-term outcomes following LuTx and identify risk factors for mortality. We retrospectively analyzed all adult patients (≥ 18years) undergoing primary and isolated LuTx between January 2000 and August 2021 at the LMU University Hospital transplant center. Using 1:1 propensity score matching, 98 corresponding pairs of LuTx patients with and without relevant CAD were identified. Among 1,003 patients having undergone LuTx, 104 (10.4%) had relevant CAD at baseline. There were no significant differences in in-hospital mortality (8.2% vs. 8.2%, p > 0.999) as well as overall survival (HR 0.90, 95%CI [0.61, 1.32], p = 0.800) between matched CAD and non-CAD patients. Similarly, cardiovascular events such as myocardial infarction (7.1% CAD vs. 2.0% non-CAD, p = 0.170), revascularization by percutaneous coronary intervention (5.1% vs. 1.0%, p = 0.212), and stroke (2.0% vs. 6.1%, p = 0.279), did not differ statistically between both matched groups. 7.1% in the CAD group and 2.0% in the non-CAD group (p = 0.078) died from cardiovascular causes. Cox regression analysis identified age at transplantation (HR 1.02, 95%CI [1.01, 1.04], p < 0.001), elevated bilirubin (HR 1.33, 95%CI [1.15, 1.54], p < 0.001), obstructive lung disease (HR 1.43, 95%CI [1.01, 2.02], p = 0.041), decreased forced vital capacity (HR 0.99, 95%CI [0.99, 1.00], p = 0.042), necessity of reoperation (HR 3.51, 95%CI [2.97, 4.14], p < 0.001) and early transplantation time (HR 0.97, 95%CI [0.95, 0.99], p = 0.001) as risk factors for all-cause mortality, but not relevant CAD (HR 0.96, 95%CI [0.71, 1.29], p = 0.788). Double lung transplant was associated with lower all-cause mortality (HR 0.65, 95%CI [0.52, 0.80], p < 0.001), but higher in-hospital mortality (OR 2.04, 95%CI [1.04, 4.01], p = 0.039). In this cohort, relevant CAD was not associated with worse outcomes and should therefore not be considered a contraindication for LuTx. Nonetheless, cardiovascular events in CAD patients highlight the necessity of control of cardiovascular risk factors and a structured cardiac follow-up.

(883) - Analysing the Utility of Single Lung Transplantation in Interstitial Lung Disease Using Discrete Event Simulation of Donor Organ Allocation

(883) - Analysing the Utility of Single Lung Transplantation in Interstitial Lung Disease Using Discrete Event Simulation of Donor Organ Allocation

Use of machine learning models for the prognostication of liver transplantation: A systematic review.

Liver transplantation (LT) is a life-saving intervention for patients with end-stage liver disease. However, the equitable allocation of scarce donor organs remains a formidable challenge. Prognostic tools are pivotal in identifying the most suitable transplant candidates. Traditionally, scoring systems like the model for end-stage liver disease have been instrumental in this process. Nevertheless, the landscape of prognostication is undergoing a transformation with the integration of machine learning (ML) and artificial intelligence models. To assess the utility of ML models in prognostication for LT, comparing their per formance and reliability to established traditional scoring systems. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, we conducted a thorough and standardized literature search using the PubMed/MEDLINE database. Our search imposed no restrictions on publication year, age, or gender. Exclusion criteria encompassed non-English stu dies, review articles, case reports, conference papers, studies with missing data, or those exhibiting evident methodological flaws. Our search yielded a total of 64 articles, with 23 meeting the inclusion criteria. Among the selected studies, 60.8% originated from the United States and China combined. Only one pediatric study met the criteria. Notably, 91% of the studies were published within the past five years. ML models consistently demonstrated satisfactory to excellent area under the receiver operating characteristic curve values (ranging from 0.6 to 1) across all studies, surpassing the performance of traditional scoring systems. Random forest exhibited superior predictive capa bilities for 90-d mortality following LT, sepsis, and acute kidney injury (AKI). In contrast, gradient boosting excelled in predicting the risk of graft-versus-host disease, pneumonia, and AKI. This study underscores the potential of ML models in guiding decisions related to allograft allocation and LT, marking a significant evolution in the field of prognostication.

Improved assessment of donor liver steatosis using Banff consensus recommendations and deep learning algorithms

The Banff Liver Working Group recently published consensus recommendations for steatosis assessment in donor liver biopsy, but few studies reported their use and no automated deep-learning algorithms based on the proposed criteria have been developed so far. We evaluated Banff recommendations on a large monocentric series of donor liver needle biopsies by comparing pathologists' scores with those generated by convolutional neural networks (CNNs) we specifically developed for automated steatosis assessment. We retrospectively retrieved 292 allograft liver needle biopsies collected between January 2016 and January 2020 and performed steatosis assessment using a former intra-institution method (pre-Banff method) and the newly introduced Banff recommendations. Scores provided by pathologists and CNN models were then compared, and the degree of agreement was measured with the intraclass correlation coefficient (ICC). Regarding the pre-Banff method, poor agreement was observed between the pathologist and CNN models for small droplet macrovesicular steatosis (ICC: 0.38), large droplet macrovesicular steatosis (ICC: 0.08), and the final combined score (ICC: 0.16) evaluation, but none of these reached statistically significance. Interestingly, significantly improved agreement was observed using the Banff approach: ICC was 0.93 for the low-power score (p <0.001), 0.89 for the high-power score (p <0.001), and 0.93 for the final score (p <0.001). Comparing the pre-Banff method with the Banff approach on the same biopsy, pathologist and CNN model assessment showed a mean (±SD) percentage of discrepancy of 26.89 (±22.16) and 1.20 (±5.58), respectively. Our findings support the use of Banff recommendations in daily practice and highlight the need for a granular analysis of their effect on liver transplantation outcomes. We developed and validated the first automated deep-learning algorithms for standardized steatosis assessment based on the Banff Liver Working Group consensus recommendations. Our algorithm provides an unbiased automated evaluation of steatosis, which will lay the groundwork for granular analysis of steatosis's short- and long-term effects on organ viability, enabling the identification of clinically relevant steatosis cut-offs for donor organ acceptance. Implementing our algorithm in daily clinical practice will allow for a more efficient and safe allocation of donor organs, improving the post-transplant outcomes of patients.

Importance and Potential of European Cross-Border Deceased Donor Organ Allocation Through FOEDUS-EOEO Platform.

The FOEDUS-EOEO platform was relaunched in 2015 to allocate deceased donor organs across European borders when there are no suitable recipients in the donor's country. We analyzed organ offers from 01.06.2015-31.12.2021 and present the number of offers and transplants, and utilization as percentage of transplanted organs. 1,483 organs were offered, 287 were transplanted (19.4% utilization). Yearly number of offers and transplants increased from 2017 to 2021, while utilization stabilized after 2018. Utilization was highest for organs offered by Slovakia (47.2%), followed for organs offered by Lithuania, France, Greece, and Czechia (19.3%-22.9%). The most frequently offered organ was the heart (n = 405; 27.3%), followed by the lungs (n = 369; 24.9%) and the liver (n = 345; 23.3%). Utilization differed significantly by organ type (highest for liver, 35.7%; followed by heart, 18.8%; and kidney, 18.3%) and by donor age (highest for 1 to 5year-old donors (25.0%)). FOEDUS-EOEO allowed for many European patients receiving a long-awaited transplant, especially for very young pediatric patients waiting for a liver, a heart, or a kidney. The increasing number of participating countries has increased both the number of offered organs and, to a lesser extent, the number of transplanted organs.

Review of pediatric combined heart-liver transplantation: A roadmap to success.

Combined heart-liver transplantation (CHLT) is a promising technique to address end stage organ failure in patients with concomitant heart failure and chronic liver disease. While most experience with CHLT has involved adult patients, the expanding population of children born with univentricular congenital heart disease who underwent the Fontan procedure and develop Fontan-associated liver disease (FALD) has emerged as a growing indication for pediatric CHLT. Currently, CHLT is performed at a select subset of experienced transplant centers, especially in the pediatric population. While technically demanding, CHLT may offer survival benefit when compared to heart transplant alone with decreased rejection of both synchronous allografts and equivalent outcomes with respect to waitlist time and post-operative complications. Limitations in the technique can be attributed to need for an appropriate multidisciplinary care center, challenges with donor organ availability and allocation, and the complexity associated with patient selection and peri-operative management. In this review, we summarize the history of CHLT, discuss patient selection, and highlight key facets of peri-operative care in the pediatric population.

Old Age and Frailty in Deceased Organ Transplantation and Allocation-A Plea for Geriatric Assessment and Prehabilitation.

Due to demographic ageing and medical progress, the number and proportion of older organ donors and recipients is increasing. At the same time, the medical and ethical significance of ageing and old age for organ transplantation needs clarification. Advanced age is associated with the frailty syndrome that has a negative impact on the success of organ transplantation. However, there is emerging evidence that frailty can be modified by suitable prehabilitation measures. Against this backdrop, we argue that decision making about access to the transplant waiting list and the allocation of donor organs should integrate geriatric expertise in order to assess and manage frailty and impairments in functional capacity. Prehabilitation should be implemented as a new strategy for pre-operative conditioning of older risk patients' functional capacity. From an ethical point of view, advanced chronological age per se should not preclude the indication for organ transplantation and the allocation of donor organs.

CARC19: An Updated Analysis of the Impact of U.S. Heart Transplantation Allocation System Change on LVAD Patients

Background: On 10/18/2018, a substantial U.S. heart transplantation (HT) allocation system change (ASC) became effective, resulting in lower priority for left ventricular assist device (LVAD) patients. While previous preliminary analyses demonstrated worse post-HT survival among LVAD patients between different eras, it remains unclear whether the presence of LVAD independently predicts unfavorable outcomes within the post-ASC period, especially among patients with expected longer wait times. Methods: Two cohorts of adult patients from the UNOS database were included, and their 1-year outcomes were analyzed. The pre-ASC and post-ASC cohorts encompassed patients listed between 10/18/2014 to 10/18/2017 and 10/18/2018 to 10/18/2021, respectively. We excluded patients listed before and transplanted after ASC. Cox regression models and competing risk analysis were performed. Results: 17,923 patients (post-ASC=9,684) were included (26.7% females, mean age of 53.4±12.5 years old). 3,873 had an LVAD (post-ASC=1,958), of which 3,003 underwent HT (post-ASC=1,515). Compared to LVAD patients transplanted in the pre-ASC era, those in the post-ASC era had shorter waitlist time; however, their grafts traveled longer distances with more prolonged ischemic time. After adjustment for potential confounders, LVAD was associated with a lower risk of waitlist mortality in both the pre- and post-ASC periods. Moreover, LVAD was associated with a lower HT rate (HR 0.74, 95% CI 0.70-0.79, p<0.001) and higher one-year post-HT mortality (HR 1.53, 95% CI 1.27-1.84, p<0.001) than those without long-term devices in the post-ASC. Notably, these differences were not observed in the pre-ASC. The association between LVAD and higher post-HT mortality was no longer seen after adjustment for the effect modification by ASC. Conclusions: Our findings suggest that LVAD therapy saves patients’ lives while waiting for HT. However, the ASC brought several changes to practice, which might be associated with increased post-HT mortality observed in patients bridged with LVAD. Further studies are needed to identify the highest-risk subgroups among LVAD patients to promote equity in donor organ allocation.

O042 Enzymatic conversion of human blood group A kidneys to universal blood group O

Abstract Introduction The ABO blood group restriction on allocation of donor organs leads to waiting time disadvantages for individuals of more restrictive blood types. Here, we outline the first preclinical use of two enzymes from Flavonifractor plautii to convert human blood group A kidneys to universal blood group O. Methods Six pairs of human kidneys rejected for transplantation and offered for research were used to in this study with approval from the National Research Ethics committee and Research and Development Office (NRES: 15/NE/0408). Three pairs were perfused for 6 h using normothermic machine perfusion (NMP), and three pairs were perfused for 24 h using hypothermic machine perfusion (HMP), with one kidney per pair randomised to enzyme treatment. Cortical biopsies collected throughout perfusion were examined for antigen loss using immunofluorescence microscopy. Results After 2hrs of NMP, a significant loss of 83.4±10.2% blood group A antigen expression was observed compared to pre-treatment levels (p=0.012), while no significant changes were observed in control kidneys (p=0.999). For HMP, a maximal loss of 71.2±21.9% was observed after 6 h (p=0.066), with no decrease observed in the contralateral controls (p=0.977). Haemodynamic perfusion parameters were stable in both cohorts, with no significant difference between control vs treated kidneys. Conclusion Our results show a loss of 70-80% of blood group A antigens in as little as 2 h of NMP and 6 h of HMP. These approaches pave the way for the first clinical studies that could herald the start of a new era that transforms donor organ allocation in kidney transplantation.

(523) Impact of the Donor Organ Allocation Change on Heart Transplant of Patients with Small Body Surface Area

(523) Impact of the Donor Organ Allocation Change on Heart Transplant of Patients with Small Body Surface Area

(525) Impact of the Donor Organ Allocation Change on Heart Transplant of Patients ≥65 Years of Age

(525) Impact of the Donor Organ Allocation Change on Heart Transplant of Patients ≥65 Years of Age

(524) Impact of the Donor Organ Allocation Change on Heart Transplant of Latinos

(524) Impact of the Donor Organ Allocation Change on Heart Transplant of Latinos

Setting Organ Allocation Priorities: A Discrete Choice Experiment with German Patients and Their Relatives.

Organ transplantation systems benefit from guidelines that are harmonious with the preferences of the people involved. Discrete choice experiments are useful tools for eliciting preferences. This study evaluated the preferences of patients and their relatives (n=285) to identify their priorities in organ allocation using a discrete choice experiment. In eight hypothetical allocation decisions, the participants were asked to select the candidate they considered the most suitable The candidates differed in years of life gained after transplantation, quality of life after transplantation, waiting time until transplantation, age, compliance and social support. The most important aspects for setting priority in organ allocation were lack of compliance (β= -2.5, p<0.001) and good quality of life after transplantation (β = +1.4, p<0.001). The lack of social support (ß = -0.8, p<0.05) and the more years of life gained after transplantation (β = +0.5, p<0.001) had less but still a significant amount of influence on this decision, while the waiting list was not considered significantly important (β = 0.1, p>0.05). The comparison of the different relations to transplantation showed that life years gained after transplantation was of high relevance to posttransplant patients (+10 years: β = +0.709, p<0.001 / +15 years: β = +0.700, p<0.001) and of no importance to waitlisted patients (+10 years: β = +0.345, p>0.05 / + 15 years: β = +0.173, p>0.05) and relatives (+ 10 years: β = +0.063, p>0.05 / +15 years: β = +0.304, p>0.05). This study provides useful insights into the unique perspective of patients and their relatives on priority-setting in the allocation of donor organs that should be reflected in improved donor organ allocation rules.

Cardiac Xenotransplantation: a New Frontier for Advanced Heart Failure.

Cardiac transplantation is a critical treatment for patients with advanced heart failure, offering the ability to markedly improve quality and quantity of life. Unfortunately, this treatment is limited by donor organ availability, despite efforts to increase organ supply and improve donor organ allocation and usage. The transplantation of non-human donor organs (xenotransplantation) offers to readily address many limitations of the current transplantation system; however, scattered attempts to establish this practice have been met with frustration. In this review, we discuss the limitations of the historical attempts and outline recent progress in the field of cardiac xenotransplantation. The advent of CRISPR-Cas9 genome editing techniques and emerging commercial and regulatory alignment has led to a flurry of new attempts to establish xenotransplantation as a viable treatment for those with end-stage heart failure. The first xenotransplantation of a genetically modified pig heart to a human recipient on January 7, 2022, highlighted the progress the science of xenotransplantation has made, as well as the need to outline next steps to further establish the practice. The development of a genetically modified porcine model has renewed hope that xenotransplantation might succeed where prior attempts failed, though many barriers remain.

Transport-Associated Vibrational Stress Triggers Drug-Reversible Apoptosis and Cardiac Allograft Failure in Mice.

Increasingly complex and long-range donor organ allocation routes coupled with implementation of unmanned aerial vehicles (UAVs) have prompted investigations of the conditions affecting organs once packaged for shipment. Our group has previously demonstrated that different modes of organ transport exert unique environmental stressors, in particular vibration. Using a mouse heart transplant model, we demonstrated that vibrational forces exert tangible, cellular effects in the form of cardiomyocyte apoptosis and cytoskeletal derangement. Functionally, these changes translated into accelerated allograft loss. Notably, administration of an apoptosis inhibitor, Z-VAD-FMK, helped to ameliorate the detrimental cellular and functional effects of mechanical vibration in a dose-dependent manner. These findings constitute one of the first reports of the negative impact of transit environment on transplant outcomes, a contributing mechanism underpinning this effect, and a potential agent to prophylax against this process. Given current limitations in measuring donor organ transit environments in situ, further study is required to better characterize the impact of transport environment and to potentially improve the care of donor organs during shipment. Clinical and Translational Impact Statement: We show that apoptosis inhibitor, Z-VAD-FMK, ameliorated transport-related vibrational stress in murine heart transplants, which presents a potential therapeutic or preservation solution additive for future use in transporting donor organs.

Deceased donor organ allocation in pediatric transplantation: Ahistorical narrative.

Since the earliest clinical successes in solid organ transplantation, the proper method of organ allocation for children has been a contentious subject. Over the past 30-35years, the medical and social establishments of various countries have favored some degree of preference for children on the respective waiting lists. However, the specific policies to accomplish this have varied widely and changed frequently between organ type and country. Organ allocation policies over time were examined. This review traces the reasons behind and the measures/principles put in place to promote early deceased donor transplantation in children. Preferred allocation in children has been approached in a variety of ways and with varying degrees of commitment in different solid organ transplant disciplines and national medical systems. The success of policies to advantage children has varied significantly by both organ and medical system. Further work is needed to optimize allocation strategies for pediatric candidates.

International Pediatric Transplant Association (IPTA) position statement supporting prioritizing pediatric recipients for deceased donor organ allocation.

A position statement of the International Pediatric Transplant Association endorsing prioritizing pediatric recipients for deceased donor organ allocation, examining the key ethical arguments that serve as the foundation for that position, and making specific policy recommendations to support prioritizing pediatric recipients for deceased donor organ allocation globally.

How Should Deceased Donor Organs Be Allocated? The Patient's Perspective Derived from Semi-Structured Interviews.

PurposeThe gap between the supply and demand for deceased donor organs is increasing worldwide, while patients on waiting lists for organ transplantation die. This situation requires ethical donor organ allocation rules. The patients’ perspective on donor organ allocation rules offers a highly relevant and unique perspective that may differ from the perspectives of physicians and the general public.Patients and MethodsSemi-structured telephone interviews were conducted with the regional group coordinators of the federal self-help organization for organ transplanted patients and their relatives in Germany in early 2021. Twelve interviews were conducted with patients and relatives of transplantation patients who received transplants for the affected organs including the lungs, heart, kidney, and liver. Transcripts were analyzed using the deductive framework method which was based on an earlier study. All criteria were reported following the COREQ statement.ResultsParticipants emphasized aspects of “medical urgency” and “effectiveness/benefit” of transplantation and associated trade-offs as well as the recipient’s responsibility for organ failure (“own fault”), the appreciation for the gifted graft and the patient’s capability of taking care of it (“appreciation/responsibility”). Patients acknowledged that urgent patients should be prioritized and they showed a clear preference toward allocation rules that strive to maximize both the life years and quality of life gained by transplantation.ConclusionThe patients’ perspective is unique in that patients agree on certain rules for allocation and share many preferences, but also have a hard time finding clear cutoff points when considering selecting a participant for allocation. Patient representatives should therefore be consulted in the debate on donor organ allocation rules.