A Roadmap for Innovation to Advance Transplant Access and Outcomes: A Position Statement From the National Kidney Foundation.

Over the past 65 years, kidney transplantation has evolved into the optimal treatment for patients with kidney failure, dramatically reducing suffering through improved survival and quality of life. However, access to transplant is still limited by organ supply, opportunities for transplant are inequitably distributed, and lifelong transplant survival remains elusive. To address these persistent needs, the National Kidney Foundation convened an expert panel to define an agenda for future research. The key priorities identified by the panel center on the needs to develop and evaluate strategies to expand living donation, improve waitlist management and transplant readiness, maximize use of available deceased donor organs, and extend allograft longevity. Strategies targeting the critical goal of decreasing organ discard that warrant research investment include educating patients and clinicians about potential benefits of accepting nonstandard organs, use of novel organ assessment technologies and real-time decision support, and approaches to preserve and resuscitate allografts before implantation. The development of personalized strategies to reduce the burden of lifelong immunosuppression and support "one transplant for life" was also identified as a vital priority. The panel noted the specific goal of improving transplant access and graft survival for children with kidney failure. This ambitious agenda will focus research investment to promote greater equity and efficiency in access to transplantation, and help sustain long-term benefits of the gift of life for more patients in need.

Access of non-residents to transplantation of deceased donor organs: practices and strategies in the European setting.

The access of non-resident patients to the deceased donor waiting list (DDWL) poses different challenges. The European Committee on Organ Transplantation of the Council of Europe (CD-P-TO) has studied this phenomenon in the European setting. A questionnaire was circulated among the Council of Europe member states to inquire about the criteria applied for non-residents to access their DDWL. Information was compiled from 28 countries. Less than 1% of recipients of deceased donor organs were non-residents. Two countries never allow non-residents to access the DDWL, four allow access without restrictions and 22 only under specific conditions. Of those, most give access to non-resident patients already in their jurisdictions who are in a situation of vulnerability (urgent life-threatening conditions). In addition, patients may be given access: (i) after assessment by a specific committee (four countries); (ii) within the framework of official cooperation agreements (15 countries); and (iii) after patients have officially lived in the country for a minimum length of time (eight countries). The ethical and legal implications of these policies are discussed. Countries should collect accurate information about residency status of waitlisted patients. Transparent criteria for the access of non-residents to DDWL should be clearly defined at national level.

Synthetic hemoglobin-based oxygen carriers are an acceptable alternative for packed red blood cells in normothermic kidney perfusion.

Normothermic machine perfusion presents a novel platform for pretransplant assessment and reconditioning of kidney grafts. Maintaining the metabolic activity of a preserved graft at physiologic levels requires an adequate oxygen supply, typically delivered by crystalloid solutions supplemented with red blood cells. In this study, we explored the feasibility of using a synthetic hemoglobin-based oxygen carrier (HBOC) in human kidney normothermic perfusion. Fourteen discarded human kidneys were perfused for 6 hours at a mean temperature of 37°C using a pressure-controlled system. Kidneys were perfused with a perfusion solution supplemented with either HBOC (n = 7) or packed red blood cells (PRBC) (n = 7) to increase oxygen-carrying capacity. Renal artery resistance, oxygen extraction, metabolic activity, energy stores, and histological features were evaluated. Throughout perfusion, kidneys from both groups exhibited comparable behavior regarding vascular flow (P = .66), oxygen consumption (P = .88), and reconstitution of tissue adenosine triphosphate (P = .057). Lactic acid levels were significantly higher in kidneys perfused with PRBC (P = .007). Histological findings were comparable between groups, and there was no evidence of histological damage caused by the HBOC. This feasibility experiment demonstrates that a HBOC solution can offer a logistically more convenient off-the-shelf alternative to PRBC in normothermic machine perfusion of human kidneys.

Measuring Critical Care Providers' Attitudes About Controlled Donation After Circulatory Death.

INTRODUCTION: Unfavorable attitudes and insufficient knowledge about donation after cardiac death among critical care providers can have important consequences for the appropriate identification of potential donors, consistent implementation of donation after cardiac death policies, and relative strength of support for this type of donation. The lack of reliable and valid assessment measures has hampered research to capture providers' attitudes. Design and Research Aims: Using stakeholder engagement and an iterative process, we developed a questionnaire to measure attitudes of donation after cardiac death in critical care providers (n = 112) and examined its psychometric properties. Exploratory factor analysis, internal consistency, and validity analyses were conducted to examine the measure. RESULTS: A 34-item questionnaire consisting of 4 factors (Personal Comfort, Process Satisfaction, Family Comfort, and System Trust) provided the most parsimonious fit. Internal consistency was acceptable for each of the subscales and the total questionnaire (Cronbach α > .70). A strong association between more favorable attitudes overall and knowledge ( r = .43, P < .001) provides evidence of convergent validity. Multivariable regression analyses showed that white race ( P = .002) and more experience with donation after cardiac death ( P < .001) were significant predictors of more favorable attitudes. CONCLUSION: Study findings support the utility, reliability, and validity of a questionnaire for measuring attitudes in critical care providers and for isolating targets for additional education on donation after cardiac death.

The need and opportunity for donation after circulatory death worldwide.

PURPOSE OF REVIEW: The global shortage of organ donors will not be resolved solely by relying on deceased donation following a brain death determination (DBD). Expansion of deceased donation after circulatory death (DCD) will be needed to address the shortfall of organs for transplantation. Approximately 120 000 organ transplants are performed each year; however, the WHO estimates that this number of transplants only resolves 10% of the annual worldwide transplant need. RECENT FINDINGS: The report addresses the opportunity of DCD expansion by evaluating the DCD potential that is not being realized, the utility of DCD enabling DBD to emerge in some clinical situations, by the effectiveness of a donor registry in achieving DCD, and by the current clinical research of heart, lung, and liver transplantation from DCD. SUMMARY: The future of deceased donation must include DCD and ex-vivo organ repair if the organ shortage is to be reconciled even partially to the ongoing demand. Although the religious and legal impediments have been overcome to determine brain death, the possibility of DCD has not been addressed. A program of DCD is feasible in all countries with transplantation services. The excellent results following kidney and lung transplantation suggest opportunities of heart and liver transplantation should be the focus of needed DCD accomplishment in the near future.

Buyer beware transplantation.

Poor long-term outcomes of commercial transplantation of transplant tourists reinforce the need to prevent this form of human trafficking. The development of an International Convention by the Council of Europe is highlighted and the implications for physicians of the criminalizing of organ trafficking are considered. The causes of poor outcomes from transplant tourism are considered, with the actions needed to provide both equity and sufficiency of access to transplantation as critical deterrent measures.

The global diffusion of organ transplantation: trends, drivers and policy implications.

Rising incomes, the spread of personal insurance, lifestyle factors adding to the burden of illness, ageing populations, globalization and skills transfer within the medical community have increased worldwide demand for organ transplantation. The Global Observatory on Donation and Transplantation, which was built in response to World Health Assembly resolution WHA57.18, has conducted ongoing documentation of global transplantation activities since 2007. In this paper, we use the Global Observatory's data to describe the current distribution of - and trends in - transplantation activities and to evaluate the role of health systems factors and macroeconomics in the diffusion of transplantation technology. We then consider the implications of our results for health policies relating to organ donation and transplantation. Of the World Health Organization's Member States, most now engage in organ transplantation and more than a third performed deceased donor transplantation in 2011. In general, the Member States that engage in organ transplantation have greater access to physician services and greater total health spending per capita than the Member States where organ transplantation is not performed. The provision of deceased donor transplantation was closely associated with high levels of gross national income per capita. There are several ways in which governments can support the ethical development of organ donation and transplantation programmes. Specifically, they can ensure that appropriate legislation, regulation and oversight are in place, and monitor donation and transplantation activities, practices and outcomes. Moreover, they can allocate resources towards the training of specialist physicians, surgeons and transplant coordinators, and implement a professional donor-procurement network.

La hausse des revenus, le développement des assurances personnelles, les facteurs de mode de vie ajoutant à la charge de morbidité des maladies, le vieillissement des populations, la mondialisation et le transfert des compétences au sein de la communauté médicale ont augmenté la demande mondiale de transplantation d'organe. L'Observatoire Mondial du Don et de la Transplantation, qui a été fondé en réponse à la résolution WHA57.18 de l'Organisation mondiale de la Santé, a rassemblé une documentation sur les activités de transplantation dans le monde de façon continue depuis 2007. Dans cet article, nous utilisons les données de l'Observatoire Mondial pour décrire la distribution actuelle (et les tendances) des activités de transplantation et pour évaluer le rôle des facteurs de systèmes de santé et de la macroéconomie dans la diffusion des technologies de transplantation. Nous considérons ensuite les implications de nos résultats sur les politiques de santé relatives au don et à la transplantation d'organe. La majorité des États Membres de l'Organisation mondiale de la Santé s'engagent maintenant dans la transplantation d'organe et plus d'un tiers d'entre eux ont réalisé des transplantations avec des organes provenant de donneurs décédés en 2011. En général, les États Membres qui se sont engagés dans la transplantation d'organe, ont un meilleur accès aux services médicaux et des dépenses totales de santé plus élevées par habitant que les États Membres où la transplantation d'organe n'est pas réalisée. La disponibilité de la transplantation avec des organes provenant de donneurs décédés était étroitement associée avec des niveaux élevés de revenu national brut par habitant. Il existe plusieurs manières possibles pour les gouvernements de soutenir le développement éthique des programmes de don et de transplantation d'organe. En particulier, ils peuvent s'assurer que la législation, la réglementation et la surveillance sont en place, et contrôler les activités, les pratiques et les résultats des dons et des transplantations. En outre, ils peuvent affecter des ressources pour la formation des médecins spécialistes, des chirurgiens et des coordinateurs de transplantation, et mettre en œuvre un réseau professionnel de recrutement des donneurs.

El aumento de la renta, la proliferación de los seguros personales y los factores del estilo de vida, sumados a la carga de enfermedades, el envejecimiento de la población, la globalización y la transferencia de conocimientos en la comunidad médica, han aumentado la demanda mundial de trasplantes de órganos. El Observatorio Mundial de Donación y Trasplante, creado en respuesta a la resolución WHA57.18 de la Asamblea Mundial de la Salud, ha llevado a cabo una documentación continua de las actividades mundiales de trasplantes desde 2007. En este informe, se emplean los datos del Observatorio Global para describir la distribución actual (y las tendencias) de las actividades de trasplante y para evaluar el papel de los factores de los sistemas sanitarios y de la macroeconomía en la difusión de la tecnología de trasplante. A continuación, se consideraron las repercusiones de los resultados en las políticas de salud relacionadas con la donación y el trasplante de órganos. En la actualidad, la mayoría de los Estados miembros de la Organización Mundial de la Salud participa en el trasplante de órganos y más de un tercio realizó trasplantes de donantes fallecidos en 2011. En general, los Estados miembros que participan en el trasplante de órganos cuentan con mayor acceso a los servicios médicos y tienen un mayor gasto total en salud per cápita que los Estados miembros donde no se realizan el trasplantes de órganos. La prestación de los trasplantes de donantes fallecidos se asoció estrechamente con altos niveles de renta nacional bruta per cápita. Existen varias formas en que los gobiernos pueden fomentar el desarrollo ético de los programas de donación y trasplante de órganos. En concreto, pueden garantizar que se adopte una legislación, regulación y supervisión adecuadas, así como realizar un seguimiento de las actividades, las prácticas y los resultados de la donación y el trasplante. Además, pueden destinar recursos a la formación de médicos especialistas, cirujanos y coordinadores de trasplantes, así como poner en marcha una red profesional de adquisición de donantes.

Acellular Perfusate is an Adequate Alternative to Packed Red Blood Cells During Normothermic Human Kidney Perfusion.

Background: Brief normothermic machine perfusion is increasingly used to assess and recondition grafts before transplant. During normothermic machine perfusion, metabolic activity is typically maintained using red blood cell (RBC)-based solutions. However, the utilization of RBCs creates important logistical constraints. This study explored the feasibility of human kidney normothermic perfusion using William's E-based perfusate with no additional oxygen carrier. Methods: Sixteen human kidneys declined for transplant were perfused with a perfusion solution containing packed RBCs or William's E medium only for 6 h using a pressure-controlled system. The temperature was set at 37 °C. Renal artery resistance, oxygen extraction, metabolic activity, energy metabolism, and histological features were evaluated. Results: Baseline donor demographics were similar in both groups. Throughout perfusion, kidneys perfused with William's E exhibited improved renal flow (P = 0.041) but similar arterial resistance. Lactic acid levels remained higher in kidneys perfused with RBCs during the first 3 h of perfusion but were similar thereafter (P = 0.95 at 6 h). Throughout perfusion, kidneys from both groups exhibited comparable behavior regarding oxygen consumption (P = 0.41) and reconstitution of ATP tissue concentration (P = 0.55). Similarly, nicotinamide adenine dinucleotide levels were preserved during perfusion. There was no evidence of histological damage caused by either perfusate. Conclusions: In human kidneys, William's E medium provides a logistically convenient, off-the-shelf alternative to packed RBCs for up to 6 h of normothermic machine perfusion.

Global initiatives to tackle organ trafficking and transplant tourism.

The increasing gap between organ supply and demand has opened the door for illegal organ sale, trafficking of human organs, tissues and cells, as well as transplant tourism. Currently, underprivileged and vulnerable populations in resource-poor countries are a major source of organs for rich patient-tourists who can afford to purchase organs at home or abroad. This paper presents a summary of international initiatives, such as World Health Organization's Principle Guidelines, The Declaration of Istanbul, Asian Task Force Recommendations, as well as UNESCO's and the United Nation's initiatives against trafficking of human organs, tissues, cells, and transplant tourism. Beyond the summary, it calls for more practical measures to be taken to implement the existing guidelines and recommendations, in order to prevent exploitation of the poor as organ providers. The paper suggests that an international legally binding agreement in criminalizing organ trafficking would be a step forward to bring a change in the global picture of organ trafficking and transplant tourism.

The alternative Iranian model of living renal transplantation.

The experience of the Iranian model should be carefully considered by those who suggest a pilot trial of a regulated market in organ sales. Mahdavi-Mazdeh's candid report makes clear that a fixed price as the basis of regulation is not possible. Iran is proceeding with an independent program of deceased organ donation in cities such as Shiraz. Mahdavi-Mazdeh's report is encouraging for the prospect of a revitalized expansion of deceased donation.

A call for government accountability to achieve national self-sufficiency in organ donation and transplantation.

Roughly 100,000 patients worldwide undergo organ transplantation annually, but many other patients remain on waiting lists. Transplantation rates vary substantially across countries. Affluent patients in nations with long waiting lists do not always wait for donations from within their own countries. Commercially driven transplantation, however, does not always ensure proper medical care of recipients or donors, and might lengthen waiting times for resident patients or increase the illegal and unethical purchase of organs from living donors. Governments should systematically address the needs of their countries according to a legal framework. Medical strategies to prevent end-stage organ failure must also be implemented. In view of the Madrid Resolution, the Declaration of Istanbul, and the 63rd World Health Assembly Resolution, a new paradigm of national self-sufficiency is needed. Each country or region should strive to provide a sufficient number of organs from within its own population, guided by WHO ethics principles.

International Travel for Liver Transplantation: A Comprehensive Assessment of the Impact on the United States Transplant System.

BACKGROUND: International travel for transplantation remains a global issue as countries continue to struggle in establishing self-sufficiency. In the United States, the United Network for Organ Sharing (UNOS) requires citizenship classification at time of waitlisting to remain transparent and understand to whom our organs are allocated. This study provides an assessment of patients who travel internationally for liver transplantation and their outcomes using the current citizenship classification used by UNOS. METHODS: Adult liver UNOS data from 2003 to 2019 were used. Patients were identified as citizens, noncitizen, nonresidents (NCNR), or noncitizen residents (NC-R) according to citizenship status. Descriptive statistics compared demographics among the waitlisted patients and demographics and donor characteristics among transplant recipients. A competing risks model was used to examine waitlist outcomes. The Kaplan-Meier method and Cox proportional hazards were used for posttransplant outcomes. RESULTS: There were significant demographic differences according to citizenship group among waitlisted (n = 125 652) and transplanted (n = 71 536) patients. Compared with US citizens, NCNR was associated with a 9% increase in transplant (subdistribution hazard ratio [SHR], 1.09; 95% confidence interval [CI], 1.00-1.18; P = 0.04), and NC-R was associated with a 24% decrease in transplant (SHR, 0.76; 95% CI, 0.72-0.79; P < 0.0001) and a 23% increase in death or removal for being too sick (SHR, 1.23; 95% CI, 1.14-1.33; P < 0.0001). US citizens had significantly inferior graft and patient survival (P < 0.001). CONCLUSIONS: Though the purpose of the citizenship classification system is transparency, the results of this study highlight significant disparities in the access to and outcomes following liver transplantation according to citizenship status.

The Reality of Inadequate Patient Care and the Need for a Global Action Framework in Organ Donation and Transplantation.

BACKGROUND: Transplant therapy is considered the best and often the only available treatment for thousands of patients with organ failure that results from communicable and noncommunicable diseases. The number of annual organ transplants is insufficient for the worldwide need. METHODS: We elaborate the proceedings of the workshop entitled "The Role of Science in the Development of International Standards of Organ Donation and Transplantation," organized by the Pontifical Academy of Sciences and cosponsored by the World Health Organization in June 2021. RESULTS: We detail the urgency and importance of achieving national self-sufficiency in organ transplantation as a public health priority and an important contributor to reaching relevant targets of the United Nations Agenda for Sustainable Development. It details the elements of a global action framework intended for countries at every level of economic development to facilitate either the establishment or enhancement of transplant activity. It sets forth a proposed plan, by addressing the technical considerations for developing and optimizing organ transplantation from both deceased and living organ donors and the regulatory oversight of practices. CONCLUSIONS: This document can be used in governmental and policy circles as a call to action and as a checklist for actions needed to enable organ transplantation as treatment for organ failure.