The attitudes of religious group leaders towards xenotransplantation: A focus group study.

Clinical trials of xenotransplantation (XTx) may start in coming years. Religious views have been mentioned as possible barriers to XTx acceptance. While there have been reports on perspectives of theologians in regard to XTx, no report has studied the perspectives of community religious leaders. A focus group was conducted with a sample of members of the following faith groups: Islam, Catholicism, and Protestantism. Qualitative content analysis was performed to identify interpretive themes. Four themes emerged. Participants were receptive to the idea of XTx and expressed no religious barriers to accepting a pig xenograft as a lifesaving therapy but did express certain concerns. Religious leaders accept the idea of XTx and do not see it as contradictory to their beliefs. However, some concerns were raised. Future studies addressing these concerns and exploring the potential role of religious leaders in educating the community on XTx are needed.

Informed Consent for Potential Recipients of Pig Kidney Xenotransplantation in the United States.

Clinical trials of kidney xenotransplantation are being considered in the United States. Before this novel procedure can take place, investigators will have to obtain approval from the institutional review board. The consent form that will be used for such a trial and that will receive approval from the institutional review board will be complex. Informed consent-the process by which a research participant provides his/her permission to participate in a clinical trial-is a staple of the research process and most commonly is in the form of a physical document. In the case of a novel procedure with uncertain benefits and risks and a participant population in acute need of a transplant, the consent process is crucial. These complexities may raise several ethical considerations for the initial pig kidney xenotransplantation recipients in the United States that will require adaptations of the required elements of the informed consent process by the US Department of Human and Health Services. The ethical issues include (1) a subject's ability to withdraw from the trial, (2) restrictions on their reproductive rights, and (3) the possibility of the need for quarantine if there is a perceived risk of xenozoonosis. This article aims to discuss ethical considerations that may challenge the general required elements of the informed consent form stipulated by the 45 Code of Federal Regulations 46 of the US Department of Health and Human Services and to suggest recommendations for deliberation.

Scientific and psychosocial ethical considerations for initial clinical trials of kidney xenotransplantation.

The initial clinical trials of pig solid organ xenotransplantation (XTx) are drawing closer and could begin in the coming years. The first clinical trials may aim to transplant genetically-modified pig kidneys into adult humans. The impetus for beginning these first-in-human trials is the severe lack of deceased donor kidneys for transplantation and the number of patients with end-stage renal disease currently on transplant waitlists, which in the USA approaches 100 000. The majority of patients on the kidney transplant waitlist receive continuous renal replacement therapy. In the United States, for patients on the kidney waitlist, the median wait-time to receive a deceased human donor organ is approximately 4.5 years for patients aged 45-74, with a 5-year mortality (or removal from the waitlist because of deteriorating health) of approximately 40%. XTx has the potential to reduce the kidney waitlist morbidity and mortality while improving quality of life. By focusing on scientific and psychosocial criteria, we present ethical considerations of certain inclusion and exclusion criteria for these first-in-human clinical trials that we suggest have not yet been fully explored.

Factors influencing attitudes toward xenotransplantation clinical trials: A report of focus group studies.

BACKGROUND: Clinical trials of xenotransplantation (XTx, ie, cross-species transplantation, specifically the transplantation of genetically engineered pig organs into human recipients) are due to start within a few years. METHODS: Five focus groups were conducted in April-May 2019, among local religious leaders (N = 10), organ procurement staff/administrators (N = 5), patients and parents of patients who may need an organ transplant or are transplant recipients (N = 9), and local businesspersons in the community (N = 3). Groups were audio-recorded, transcribed, and analyzed with NVivo software to identify themes of participants' thoughts to XTx. RESULTS: An overall Cohen's kappa statistic of 0.71 was established. In general, there was wide agreement among participants that XTx is an exciting and acceptable option to explore as an organ alternative. Concerns were expressed primarily regarding issues of animal ethics, stigma regarding how pigs are viewed in society, organ allocation logistics, quality of life after receiving a xenograft, and how XTx would be accepted by certain theological traditions. CONCLUSION: Overall, various stakeholders accepted XTx as a clinical option. However, there were ethical, social, and physical concerns raised. Future studies exploring the development of education strategies that may help alleviate concerns related to XTx before it becomes a clinical alternative are needed among the general public, potential XTx candidates, and their family members.

Attitudes toward xenotransplantation: A survey of parents and pediatric cardiac providers.

BACKGROUND: Scientific advancements are occurring in cardiac xenotransplantation (XTx). However, there have been religious and social concerns surrounding this allotransplantation alternative. The purpose of this study was to explore the acceptance of XTx among stakeholders of the congenital heart disease (CHD) community. METHODS: A Likert-scale anonymous survey was distributed to physicians and nurses who care for children with CHD and parents of children with CHD. Psychosocial and clinical attitudes were compared across all groups to identify differences, and regression analysis was performed to identify factors associated with XTx acceptance. RESULTS: A total of 297 responded to the survey: 134 physicians, 62 nurses, and 101 parents. Potential acceptance of XTx if outcomes were similar to allotransplantation was high overall (75.3%), but different between the groups (physicians 86%; nurses 71%, parents 64%; P < .0001). Regression analysis showed respondents who reported religion would influence medical decision making (OR 0.48; 95%CI 0.24-0.97) and those who would not use a pig heart transplant as a bridge until a human heart became available were less likely to accept XTx (OR 0.09; 95%CI 0.04-0.21). Psychosocial concerns to XTx were minimal but were also associated with XTx acceptance particularly among parents (OR 0.17; 95%CI 0.03-0.80). CONCLUSIONS: Potential acceptance of XTx is high, assuming results are similar to allotransplantation. Religious beliefs and attitudes toward the use of XTx as a bridge to allotransplant may present barriers to XTx acceptance. Future research is needed to assess potential attitude differences in light of ethical, psychosocial, and religious objections to XTx.

Pig kidney xenotransplantation: Progress toward clinical trials.

Pig organ xenotransplantation offers a solution to the shortage of deceased human organs for transplantation. The pathobiological response to a pig xenograft is complex, involving antibody, complement, coagulation, inflammatory, and cellular responses. To overcome these barriers, genetic manipulation of the organ-source pigs has largely been directed to two major aims-(a) deletion of expression of the known carbohydrate xenoantigens against which humans have natural (preformed) antibodies, and (b) transgenic expression of human protective proteins, for example, complement- and coagulation-regulatory proteins. Conventional (FDA-approved) immunosuppressive therapy is unsuccessful in preventing an adaptive immune response to pig cells, but blockade of the CD40:CD154 costimulation pathway is successful. Survival of genetically engineered pig kidneys in immunosuppressed nonhuman primates can now be measured in months. Non-immunological aspects, for example, pig renal function, a hypovolemia syndrome, and rapid growth of the pig kidney after transplantation, are briefly discussed. We suggest that patients on the wait-list for a deceased human kidney graft who are unlikely to receive one due to long waiting times are those for whom kidney xenotransplantation might first be considered. The potential risk of infection, public attitudes to xenotransplantation, and ethical, regulatory, and financial aspects are briefly addressed.

Racial differences in attitudes to clinical pig organ Xenotransplantation.

INTRODUCTION: In addition to an organ donor shortage, racial disparities exist at different stages of the transplantation process. Xenotransplantation (XTx) could alleviate these issues. This study describes racial differences in attitudes to XTx among populations who may need a transplant or are transplant recipients. METHODS: A Likert-scale survey was distributed at outpatient clinics to parents of children with congenital heart disease (CHD) and kidney patients on their attitudes to pig organ XTx. Data from these two groups were stratified by race and compared. RESULTS: Ninety-seven parents of children with CHD (74.2% White and 25.8% Black) and 148 kidney patients (50% White and 50% Black) responded to our survey. Black kidney patients' acceptance of XTx although high (70%) was lower than White kidney patients (91%; P .003). White kidney patients were more likely to accept XTx if results are similar to allotransplantation (OR 4.14; 95% CI 4.51-11.41), and less likely to be concerned with psychosocial changes when compared to Black kidney patients (receiving a pig organ would change your personality OR 0.08; 95% CI 0.01-0.67 and would change social interaction OR 0.24; 95% CI 0.07-0.78). There were no racial differences in attitudes to XTx among parents of children with CHD. CONCLUSION: There are differences in attitudes to XTx particularly among Black kidney patients. Because kidneys may be the first organ for clinical trials of XTx, future studies that decrease scientific mistrust and XTx concerns among the Black community are needed to prevent disparities in uptake of possible future organ transplant alternatives.

Attitudes to Cardiac Xenotransplantation by Pediatric Heart Surgeons and Physicians.

BACKGROUND: Cardiac transplantation in early childhood is limited by scarcity of organ donors. Advances in cardiac xenotransplantation (XTx) research suggest that xenografts may one day represent an alternative to allografts. We sought to determine the attitudes among surgeons and cardiologists in the field of pediatric cardiac transplantation toward the potential use of XTx if this clinical option were to become a reality. METHODS: A Likert-scale anonymous survey addressing the use of XTx in pediatric patients was sent to members of the Congenital Heart Surgeons (CHS) Society and the Pediatric Heart Transplant Society. Results were described and compared between the two surgeon/physician groups. RESULTS: Ninety-two CHS and 42 pediatric transplant cardiologists (PTC) responded (N = 134). The potential acceptance of XTx was high in both groups, assuming risks and results were similar to those of cardiac allotransplantation (88% CHS vs 81% PTC; P = .07). When asked if they would recommend a xenograft, if the results were anticipated to be inferior to those of cardiac allotransplantation, as a bridge to a human heart, potential acceptance fell dramatically but remained higher among CHS than PTC (41% vs 17%, p 0.02). Approximately only one-third of CHS and half of PTC preferred primary cardiac XTx for hypoplastic left heart syndrome if there was no waitlist time and had similar outcomes to allotransplantation. CONCLUSIONS: Our findings suggest that potential acceptance of XTx by CHS and PTC would not be a major barrier if XTx demonstrated similar outcomes to allotransplantation. Acceptance by other congenital heart stakeholders remains to be investigated.

Meta-analysis of public perception toward xenotransplantation.

The shortage of donor organs for transplantation is an international problem. One promising option to meet the need is xenotransplantation (XTx; eg, pig-to-human). However, there are still questions surrounding XTx that must be answered before proceeding to clinical trials. The current work is a meta-analysis of articles published between 1985 and 2019 to analyze the factors most strongly associated with agreement and opposition toward the procedure. Although 80% (41/51) of the published studies were related to the opinions of patients, only three provided sufficient data for analysis. Thus, the bulk of what we really know about attitudes toward XTx comes from students, stakeholders, and hospital staff. The findings suggest that, before proceeding from the laboratory to clinical trials, more directed research is necessary from individual programs to achieve sufficient understanding of the attitudes of patients and the broader public, and the level of risk that is acceptable to these groups.

Attitudes to Clinical Pig Kidney Xenotransplantation among Medical Providers and Patients.

Background: In addition to governmental regulation and scientific advancements, the World Health Organization requires extensive review of local opinions before initiating clinical trials of xenotransplantation (XTx). The purpose of this study was to assess the attitudes of health care providers and patients regarding XTx. Methods: An anonymous Likert-scale survey regarding attitudes toward XTx was distributed to pre- and post-kidney transplant patients, nephrologists, transplant surgeons, and nurses ("providers"). Patient and provider responses were described and compared. Regression analysis using patients' responses was performed to identify factors associated with XTx acceptance. Results: Eighty percent (32/40) of providers and 69% (113/163) of patients were agreeable to clinical XTx if the risks and results were likely to be similar to kidney allotransplantation (P<0.05). Kidney providers rated the influence of religious beliefs in medical decisions (45% versus 15%) and genetic engineering (43% versus 25%) as being more important than did patients (P<0.05). A small proportion in both groups (<15%) reported concerns about (1) potential personality changes, (2) how others would interact, (3) a perception of being "less human," or (4) morals or ethics. Logistic regression found that the odds of patients accepting XTx were greater if they had no religious concerns (OR, 25.10; 95% CI, 2.59 to 243.00), but acceptance was less likely if they were not willing to use XTx as a bridge to allotransplantation (OR, 0.18; 95% CI, 0.51 to 0.70). Conclusions: (1) If outcomes were similar to allotransplantation, XTx support was strong among both providers and patients; (2) providers overestimated the influence of religious beliefs and genetic engineering on patient medical decisions, although religious beliefs are associated with XTx acceptance; (3) XTx use as a bridge to allotransplant was associated with XTx acceptance; and (4) psychosocial concerns were low for either group. Future studies among other communities are warranted to assess if similar attitudes exist.

Paediatric xenotransplantation clinical trials and the right to withdraw.

Clinical trials of xenotransplantation (XTx) may begin early in the next decade, with kidneys from genetically modified pigs transplanted into adult humans. If successful, transplanting pig hearts into children with advanced heart failure may be the next step. Typically, clinical trials have a specified end date, and participants are aware of the amount of time they will be in the study. This is not so with XTx. The current ethical consensus is that XTx recipients must consent to lifelong monitoring. While this presents challenges to the right to withdraw in the adult population, additional and unanswered questions also linger in the paediatric population. In paediatric XTx, parents or guardians consent not only to the initial treatment of the child but also to lifelong monitoring, thus making a decision whose consequences will remain present as the child develops the capacity for assent, and finally the capacity for informed consent or refusal. This article presents and evaluates unanswered paediatric ethical questions in regard to the right to withdraw from XTx follow-up in the paediatric population.

Jewish, Christian and Muslim theological perspectives about xenotransplantation.

BACKGROUND: This paper is based on a theological symposium presented at the International Xenotransplantation Association's 14th Congress held in Baltimore, MD, September, 2017. METHODS: The information explores the Jewish, Christian and Muslim theological perceptions and perspectives about cross-species (ie pig-to-human) organ transplantation, the genetic alterations required in the organ-source pig, and their potential to influence individual acceptance of the procedure. RESULTS/CONCLUSIONS: This work should not be considered as the ultimate word about individual theological views, but rather as part of an ongoing conversation that will hopefully lead to wider consideration and exploration of these issues as xenotransplantation science advances towards clinical trials.

Renal xenotransplantation: experimental progress and clinical prospects.

There are >100,000 patients waiting for kidney transplants in the United States and a vast need worldwide. Xenotransplantation, in the form of the transplantation of kidneys from genetically engineered pigs, offers the possibility of overcoming the chronic shortage of deceased and living human donors. These genetic manipulations can take the form of (i) knockout of pig genes that are responsible for the expression of antigens against which the primate (human or nonhuman primate) has natural "preformed" antibodies that bind and initiate complement-mediated destruction or (ii) the insertion of human transgenes that provide protection against the human complement, coagulation, or inflammatory responses. Between 1989 and 2015, pig kidney graft survival in nonhuman primates increased from 23 days to almost 10 months. There appear to be no clinically significant physiological incompatibilities in renal function between pigs and primates. The organ-source pigs will be housed in a biosecure environment, and thus the risk of transferring an exogenous potentially pathogenic microorganism will be less than that after allotransplantation. Although the risk associated with porcine endogenous retroviruses is considered small, techniques are now available whereby they could potentially be excluded from the pig. The US Food and Drug Administration suggests that xenotransplantation should be restricted to "patients with serious or life-threatening diseases for whom adequately safe and effective alternative therapies are not available." These might include those with (i) a high degree of allosensitization to human leukocyte antigens or (ii) rapid recurrence of primary disease in previous allografts. The potential psychosocial, regulatory, and legal aspects of clinical xenotransplantation are briefly discussed.

Organ transplantation in Egypt.

Concern has increasingly been expressed about the growing number of reports of medical personnel participating in the transplantation of human organs or tissues taken from the bodies of executed prisoners, handicapped patients, or poor persons who have agreed to part with their organs for commercial purposes. Such behavior has been universally considered as ethically and morally reprehensible, yet in some parts of the world the practice continues to flourish. The concept of justice demands that every person have an equal right to life, and to protect this right, society has an obligation to ensure that every person has equal access to medical care. Regrettably, the Egyptian system does not legally recognize brain death and continues to allow the buying and selling of organs. For more than 30 years in Egypt, the ability to pay has determined who receives an organ and economic need has determined who will be the donor. As transplant professionals, it is important that we advocate on behalf of all patients, potential recipients, and donors and for those who are left out and not likely to receive a donor organ in an economically based system. Current issues associated with this debate are reviewed and recommendations about how to address them in Egypt are discussed.