Ethical analysis examining the prioritisation of living donor transplantation in times of healthcare rationing

The transplant community has faced unprecedented challenges balancing risks of performing living donor transplants during the COVID-19 pandemic with harms of temporarily suspending these procedures. Decisions regarding postponement of living donation stem from its designation as an elective procedure, this despite that the Centers for Medicare and Medicaid Services categorise transplant procedures as tier 3b (high medical urgency—do not postpone). In times of severe resource constraints, health systems may be operating under crisis or contingency standards of care. In this manuscript, the United Network for Organ Sharing Ethics Workgroup explores prioritisation of living donation where health systems operate under contingency standards of care and provide a framework with recommendations to the transplant community on how to approach living donation in these circumstances.To guide the transplant community in future decisions, this analysis suggests that: (1) living donor transplants represent an important option for individuals with end-stage liver and kidney disease and should not be suspended uniformly under contingency standards, (2) exposure risk to SARS-CoV-2 should be balanced with other risks, such as exposure risks at dialysis centres. Because many of these risks are not quantifiable, donors and recipients should be included in discussions on what constitutes acceptable risk, (3) transplant hospitals should strive to maintain a critical transplant workforce and avoid diverting expertise, which could negatively impact patient preparedness for transplant, (4) transplant hospitals should consider implementing protocols to ensure early detection of SARS-CoV-2 infections and discuss these measures with donors and recipients in a process of shared decision-making.

Kidney Paired Exchanges and Variants

Given the growing gap between the demand and supply of kidneys needed for transplantation, and the better outcomes of living versus deceased donor kidney transplants, living kidney donation is being more aggressively endorsed and promoted. Traditionally, living kidney donors were ABO- and HLA-compatible with their recipients, with whom they were genetically and/or emotionally related. When a living donor-recipient pair is not compatible, there is growing acceptance of employing alternative living donor transplantation strategies such as paired kidney exchanges and domino chains. This chapter addresses the ethical and policy issues that are raised by participation in kidney paired exchanges and domino kidney chains. Specific attention is given to the participation of histocompatible donor-recipient pairs in these programs when the donor could just donate directly. Justice and other ethical issues raised by advance donor programs and list-paired exchanges are also discussed.

Developing a Living Donor Ethics Framework

This chapter advances an ethical framework for living donor transplantation. Given the analogies between living donor transplantation and human subjects research, the three principles enumerated in the National Commission’s Belmont Report are adopted as the starting point: respect for persons, beneficence, and justice. Two additional principles are also adopted: the principle of vulnerability and the principle that special relationships create special obligations. Whereas the Belmont Report discussed vulnerable groups, vulnerability is more aptly understood as an assortment of vulnerabilities that may apply to different people in different circumstances at different times of their lives. Eight distinct but overlapping vulnerabilities are described: capacitational, juridic, deferential, social, medical, situational, allocational, and infrastructural. The living donor advocate team (LDAT) stands in special relationship with the potential living donor and supports living organ donation provided that the living donor successfully addresses the challenges to autonomy and voluntariness that these vulnerabilities pose.

Increasing the Rate of Living Donor Kidney Transplantation in New Zealand: Developing an Evidence Base

<p>Increasing numbers of New Zealanders are experiencing end-stage renal failure, requiring kidney transplantation or dialysis. A transplant from a living kidney donor is the preferred treatment, offering better quality of life than dialysis, and greater life expectancy and cost-effectiveness than dialysis and deceased donor transplantation. Living donor transplant rates in New Zealand have plateaued and may even be declining at a time when many comparable countries are experiencing sustained increases. Viewing this issue as a complex policy problem, this research aimed to identify how rates of living donor kidney transplantation could be increased in New Zealand. Based on Walt and Gilson’s health policy triangle, which suggests that understanding policy issues requires attention not only to content (policy options) but also processes, contextual issues and actors, this research asked firstly, what the barriers are for patients in the journey to living donor transplantation, and secondly, why greater attention has not been paid to how to increase current rates, given evidence of better outcomes for patients and cost-effectiveness. The research took a patient-centred, systems perspective and used a pragmatic, interdisciplinary, mixed-methods research design. Methods included a survey of kidney transplant waiting-list patients; interviews with patients, renal health professionals and key informants; document analysis; and a survey of health managers. A Five-Stage Model of the living donor kidney transplant process was developed to map specific barriers in the journey to transplantation and Kingdon’s multiple streams agenda-setting model was used to examine the issue of why so little attention had been paid to living donor kidney transplantation in New Zealand. The research found that, in common with patients elsewhere, New Zealand patients are not systematically informed about living donor transplantation, would like to receive a transplant but have concerns about health and financial impacts on donors, and face challenges in approaching people in their networks about living donation. Incompatibility and medical unsuitability are major barriers for potential donors who do come forward. Issues with existing service models, configuration of key roles in transplant services, and delays in donor work-up processes are all evident. Perceived ethical constraints may limit how willing health professionals are to promote living donation, requiring both potential recipients and donors to be very proactive to successfully navigate the living donation process. There has been political will to address organ shortages in the past but there has been little focus specifically on live donation. An absence of feasible and acceptable options for decision-makers to consider, crowding-out by demand for dialysis services, lack of leadership, absence of an effective advocate, and issues in funding and accountability arrangements may all have contributed to why live kidney transplantation has not had more prominence on the policy agenda in New Zealand in recent years. Overall, the research concludes that policy and practice in the wider system are not adequately oriented to supporting living donor kidney transplantation as the preferred treatment for end-stage renal failure. A comprehensive national strategy for increasing New Zealand’s rate is recommended.</p>

Increasing the Rate of Living Donor Kidney Transplantation in New Zealand: Developing an Evidence Base

<p>Increasing numbers of New Zealanders are experiencing end-stage renal failure, requiring kidney transplantation or dialysis. A transplant from a living kidney donor is the preferred treatment, offering better quality of life than dialysis, and greater life expectancy and cost-effectiveness than dialysis and deceased donor transplantation. Living donor transplant rates in New Zealand have plateaued and may even be declining at a time when many comparable countries are experiencing sustained increases. Viewing this issue as a complex policy problem, this research aimed to identify how rates of living donor kidney transplantation could be increased in New Zealand. Based on Walt and Gilson’s health policy triangle, which suggests that understanding policy issues requires attention not only to content (policy options) but also processes, contextual issues and actors, this research asked firstly, what the barriers are for patients in the journey to living donor transplantation, and secondly, why greater attention has not been paid to how to increase current rates, given evidence of better outcomes for patients and cost-effectiveness. The research took a patient-centred, systems perspective and used a pragmatic, interdisciplinary, mixed-methods research design. Methods included a survey of kidney transplant waiting-list patients; interviews with patients, renal health professionals and key informants; document analysis; and a survey of health managers. A Five-Stage Model of the living donor kidney transplant process was developed to map specific barriers in the journey to transplantation and Kingdon’s multiple streams agenda-setting model was used to examine the issue of why so little attention had been paid to living donor kidney transplantation in New Zealand. The research found that, in common with patients elsewhere, New Zealand patients are not systematically informed about living donor transplantation, would like to receive a transplant but have concerns about health and financial impacts on donors, and face challenges in approaching people in their networks about living donation. Incompatibility and medical unsuitability are major barriers for potential donors who do come forward. Issues with existing service models, configuration of key roles in transplant services, and delays in donor work-up processes are all evident. Perceived ethical constraints may limit how willing health professionals are to promote living donation, requiring both potential recipients and donors to be very proactive to successfully navigate the living donation process. There has been political will to address organ shortages in the past but there has been little focus specifically on live donation. An absence of feasible and acceptable options for decision-makers to consider, crowding-out by demand for dialysis services, lack of leadership, absence of an effective advocate, and issues in funding and accountability arrangements may all have contributed to why live kidney transplantation has not had more prominence on the policy agenda in New Zealand in recent years. Overall, the research concludes that policy and practice in the wider system are not adequately oriented to supporting living donor kidney transplantation as the preferred treatment for end-stage renal failure. A comprehensive national strategy for increasing New Zealand’s rate is recommended.</p>

Formative Usability of the Kidneytime Online Live Donor Kidney Transplant Education Tool Among Transplant Candidates

Background Web-based education may be a powerful tool to support transplant candidates’ learning and communication about live donor kidney transplantation. Few educational interventions are web-based and have education sharing for living donor transplant as a primary goal. Methods Through user-centered design and iterative usability testing, we developed a web platform, called KidneyTIME, to support an educational intervention for adult transplant candidates. KidneyTIME delivers animated videos to improve candidate knowledge, motivation, and self-efficacy to pursue living donor transplantation and to promote outreach through video sharing. The animated-video educational content was previously produced by the researchers. We conducted a formative usability evaluation of the KidneyTIME web platform to enable users to find, view, and share the previously produced videos. A total of 30 kidney transplant candidates were involved in 4 rounds of testing at one transplant center, with amendments made after each round. Results Transplant candidates were predominantly White non-Hispanic; 47% had incomes <$30 000 and >43% had vision or motor impairment. Readability, navigation, and failure to find videos were the main usability issues identified. Substantial improvements were found in the usability of most functions after implementing certain features, such as enlarging text and buttons, enhancing contrast, and simplifying presentation. Participants reported that the intervention was user friendly and easy to navigate. Conclusion Considering feedback from a wide spectrum of users has improved the usability of KidneyTIME. A salient concern for End stage kidney disease populations is ensuring online accessibility despite vision and motor impairments.

Selective HIF stabilization alleviates hepatocellular steatosis and ballooning in a rodent model of 70% liver resection

Background: Small-for-size syndrome looms over patients needing liver resection or living-donor transplantation. Hypoxia has been shown to be crucial for the successful outcome of liver resection in the very early postoperative phase. While poorly acceptable as such in real-world clinical practice, hypoxia responses can still be simulated by pharmacologically raising levels of its transducers, the hypoxia-inducible factors (HIF). We aimed to assess the potential role of a selective inhibitor of HIF degradation in 70% hepatectomy (70%Hx). Methods: In a pilot study, we tested the required dose of roxadustat to stabilize liver HIF1α. We then performed 70%Hx in 8-week-old male Lewis rats and administered 25 mg/kg of roxadustat (RXD25) at the end of the procedure. Regeneration was assessed: ki67 and EdU immunofluorescent labeling, and histological parameters. We also assessed liver function via a blood panel and functional gadoxetate-enhanced magnetic resonance imaging, up to 47 hours after the procedure. Metabolic results were analyzed by means of RNA sequencing. Results: Roxadustat effectively increased early HIF1α transactivity. Liver function did not appear to be improved nor liver regeneration to be accelerated by the experimental compound. However, treated livers showed a mitigation in hepatocellular steatosis and ballooning, known markers of cellular stress after liver resection. RNA sequencing confirmed that roxadustat unexpectedly increases lipid breakdown and cellular respiration. Conclusions: Selective HIF stabilization did not result in an enhanced liver function after standard liver resection, but it induced interesting metabolic changes that are worth studying for their possible role in extended liver resections and fatty liver diseases.

Barriers to the Donation of Living Kidneys for Kidney Transplantation

Since the waiting time for deceased donor kidney transplantation continues to increase, living donor kidney transplantation is an important treatment for end stage kidney disease patients. Barriers to living kidney donation have been rarely investigated despite a growing interest in the utilization of living donor transplantation and the satisfaction of donor safety. Here, we retrospectively analyzed 1,658 potential donors and 1,273 potential recipients who visited the Seoul National University Hospital for living kidney transplantation between 2010 and 2017 to study the causes of donation failure. Among 1,658 potential donors, 902 (54.4%) failed to donate kidneys. The average number of potential donors that received work-up was 1.30 ± 0.66 per recipient. Among living donor kidney transplant patients, 75.1% received kidneys after work-up of the first donor and 24.9% needed work-up of two or more donors. Donor-related factors (49.2%) were the most common causes of donation failure, followed by immunologic or size mismatches between donors and recipients (25.4%) and recipient-related factors (16.2%). Interestingly, withdrawal of donation will along with refusal by recipients or family were the commonest causes, suggesting the importance of non-biomedical aspects. The elucidation of the barriers to living kidney donation could ensure more efficient and safer living kidney donation.