Introduction: Much of the higher risk for end-stage kidney disease (ESKD) in African American individuals relates to ancestry-specific variation in the apolipoprotein L1 gene (APOL1). Relative to kidneys from European American deceased-donors, kidneys from African American deceased-donors have shorter allograft survival and African American living-kidney donors more often develop ESKD. The National Institutes of Health (NIH)-sponsored APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO) is prospectively assessing kidney allograft survival from donors with recent African ancestry based on donor and recipient APOL1 genotypes. Methods: APOLLO will evaluate outcomes from 2614 deceased kidney donor-recipient pairs, as well as additional living-kidney donor-recipient pairs and unpaired deceased-donor kidneys. Results: The United Network for Organ Sharing (UNOS), Association of Organ Procurement Organizations, American Society of Transplantation, American Society for Histocompatibility and Immunogenetics, and nearly all U.S. kidney transplant programs, organ procurement organizations (OPOs), and histocompatibility laboratories are participating in this observational study. APOLLO employs a central institutional review board (cIRB) and maintains voluntary partnerships with OPOs and histocompatibility laboratories. A Community Advisory Council composed of African American individuals with a personal or family history of kidney disease has advised the NIH Project Office and Steering Committee since inception. UNOS is providing data for outcome analyses. Conclusion: This article describes unique aspects of the protocol, design, and performance of APOLLO. Results will guide use of APOL1 genotypic data to improve the assessment of quality in deceased-donor kidneys and could increase numbers of transplanted kidneys, reduce rates of discard, and improve the safety of living-kidney donation.

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Introduction: Tests exist for ApoL1 genetic variants to determine whether a potential donor’s kidneys are at increased risk of kidney failure. Variants of the ApoL1 gene associated with increased risk are primarily found in people with West African ancestry. Given uncertainty about clinical implications of ApoL1 test results for living kidney donors and recipients and the lack of uniform guidelines for ApoL1 testing, transplant centers across the United States vary in ApoL1 testing practices. Research Questions: (1) What approach do transplant centers take to determine whether prospective donors are of West African ancestry? (2)How do transplant centers engage potential donors during the ApoL1 testing process? (3) What do transplant centers identify as concerns and barriers to ApoL1 testing? and (4) What actions do transplant centers take when a potential donor has 2 ApoL1 risk variants? Design: We explored the current practices of transplant centers by surveying nephrologists and transplant surgeons at transplant centers evaluating the majority of black living donors in the United States. Results: About half of these transplant centers offered ApoL1 testing. Of those who offered ApoL1 testing, only half involved the donor in decision-making about donation when the donor has 2 risk variants. Discussion: Unaddressed differences in the priorities of transplant centers and black living donors may stigmatize black donors and undermine trust in the health-care and organ donation systems. Variation in transplant center testing practices points to the critical need for further research and community engagement to inform the development of guidelines for ApoL1 testing.

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BackgroundIn 2004, patient advocate groups were major players in helping pass and implement significant public policy and funding initiatives in stem cells and regenerative medicine. In the following years, advocates were also actively engaged in Washington DC, encouraging policy makers to broaden embryonic stem cell research funding, which was ultimately passed after President Barack Obama came into office. Many advocates did this because they were told stem cell research would lead to cures. After waiting more than 10 years, many of these same patients are now approaching clinics around the world offering experimental stem cell-based interventions instead of waiting for scientists in the US to complete clinical trials. How did the same groups who were once (and often still are) the strongest supporters of stem cell research become stem cell tourists? And how can scientists, clinicians, and regulators work to bring stem cell patients back home to the US and into the clinical trial process?DiscussionIn this paper, we argue that the continued marketing and use of experimental stem cell-based interventions is problematic and unsustainable. Central problems include the lack of patient protection, US liability standards, regulation of clinical sites, and clinician licensing. These interventions have insufficient evidence of safety and efficacy; patients may be wasting money and time, and they may be forgoing other opportunities for an intervention that has not been shown to be safe and effective. Current practices do not contribute to scientific progress because the data from the procedures are unsuitable for follow-up research to measure outcomes. In addition, there is no assurance for patients that they are receiving the interventions promised or of what dosage they are receiving. Furthermore, there is inconsistent or non-existent follow-up care. Public policy should be developed to correct the current situation.ConclusionThe current landscape of stem cell tourism should prompt a re-evaluation of current approaches to study cell-based interventions with respect to the design, initiation, and conduct of US clinical trials. Stakeholders, including scientists, clinicians, regulators and patient advocates, need to work together to find a compromise to keep patients in the US and within the clinical trial process. Using HIV/AIDS and breast cancer advocate cases as examples, we identify key priorities and goals for this policy effort.

In 2006, the Institute of Medicine (IOM) recommended demonstration projects on uncontrolled donation after cardiac death or rapid organ recovery (ROR). To investigate what the public thinks about key ethical and policy questions associated with ROR, 70 AfricanAmerican, Caucasian and Latino community members in St. Louis, MO, participated in focus groups and completed surveys, before and after being educated about ROR. Before the focus group, most participants believed mistakenly that they could donate organs following an unexpected cardiac arrest (76%). After the focus group, 84% would want to donate organs after unexpected cardiac arrest; 81% would support organ cooling to enable this. The public generally supported organ cooling without family consent if the individual had joined the donor registry, but were mixed in their opinions about what should be done if they were not on the registry. African-American and Latino participants expressed greater fears than Caucasians that if they consented to organ donation, physicians might do less to save their life; however, support for ROR was not significantly lower in these subgroups. Although this study is exploratory, public support for ROR was present. We recommend that adequate consent processes and safeguards be established to foster trust and support for ROR.

Clinical investigators must engage in just subject recruitment and selection and avoid unduly influencing research participation. There may be tension between the practice of keeping payments to participants low to avoid undue influence and the requirements of justice when recruiting normal healthy volunteers for phase 1 drug studies. By intentionally keeping payments low to avoid unduly influenced participation, investigators, on the recommendation or insistence of institutional review boards, may be targeting or systematically recruiting healthy adult members of lower socio-economic groups for participation in phase 1 studies. Investigators are at risk of routinely failing to fulfill the obligation of justice, which prohibits the systematic targeting and recruiting of subjects for reasons unrelated to the nature of the study. Insofar as we take seriously the obligation to engage in just subject recruitment and selection, I argue that we must acknowledge the implications low payments might have for subject recruitment and selection and examine the effect of low payments. If low payments de facto target the less well-off for phase 1 studies, we must defend the priority ranking of the obligation to avoid undue influence over the obligation of justice or adopt an alternative recruitment approach. This paper identifies a number of alternatives to the current system of low-value payments to research participants.

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