Improving Kidney Disease Research in the Black Community: The Essential Role of Black Voices in the APOLLO Study
2021; Elsevier BV; Volume: 79; Issue: 5 Linguagem: Inglês
10.1053/j.ajkd.2021.09.006
ISSN1523-6838
AutoresAna S. Iltis, Alexis D. Conell, Lori A. Cooper, Patrick O. Gee, Nichole Jefferson, Heather A. Johnson, Giftay Myah Kingston, Glenda V. Roberts, Norman M. Scott, Angenetta Smith, Salina P. Waddy, Leslie Woodard, James M. DuBois,
Tópico(s)Renal and Vascular Pathologies
ResumoFEATURE EDITORDaniel E. WeinerADVISORY BOARDL. Ebony BoulwareKevin EricksonEduardo Lacson JrBruce M. RobinsonWolfgang WinkelmayerPolicy Forum highlights aspects of nephrology relating to payment and social policy, legislation, regulation, demographics, politics, and ethics, contextualizing these issues as they relate to the lives and practices of members of the kidney community, including providers, payers, and patients. FEATURE EDITOR Daniel E. Weiner ADVISORY BOARD L. Ebony Boulware Kevin Erickson Eduardo Lacson Jr Bruce M. Robinson Wolfgang Winkelmayer Policy Forum highlights aspects of nephrology relating to payment and social policy, legislation, regulation, demographics, politics, and ethics, contextualizing these issues as they relate to the lives and practices of members of the kidney community, including providers, payers, and patients. The National Institutes of Health (NIH)–funded APOL1 Long-Term Kidney Transplantation Outcomes (APOLLO) study involves genetic testing of biospecimens from up to 700 Black living kidney donors and 1,300 Black deceased kidney donors and will also test and track outcomes among racially diverse recipients of those kidneys.1Freedman B.I. Moxey-Mims M. The APOL1 long-term kidney transplantation outcomes network—APOLLO.Clin J Am Soc Nephrol. 2018; 13: 940-942https://doi.org/10.2215/CJN.01510218Google Scholar Given the racially targeted nature of APOLLO, the history of racism in the United States, and the current social background, this study cannot succeed without appropriately hearing and responding to the Black community's study-related concerns and hopes. The Community Advisory Council (CAC) has been integral to APOLLO, providing direction and oversight.2Kimmel P.L. Jefferson N. Norton J.M. Star R.A. How community engagement is enhancing NIDDK research.Clin J Am Soc Nephrol. 2019; 14: 768-770https://doi.org/10.2215/CJN.14591218Google Scholar The CAC was involved in developing the protocol, consent forms, manual of procedures, informational materials, and many other documents. The CAC's voice was instrumental during the startup phase and continues to shape study policy and decisions. We describe the study, the CAC, and the CAC's overarching points of guidance thus far, as this may be instructive to other research projects that target specific communities in the United States. In this discussion, "Black" refers to people with African ancestry including those who identify as African American. People with 2 copies of the risk variants in the apolipoprotein L1 gene (APOL1), termed G1 and G2, are more likely to develop kidney disease than those with 0 or 1 copy, yet most do not develop kidney disease.3Freedman B.I. Kopp J.B. Langefeld C.D. et al.The apolipoprotein L1 (APOL1) gene and nondiabetic nephropathy in African Americans.J Am Soc Nephrol. 2010; 21: 1422-1426https://doi.org/10.1681/ASN.2010070730Google Scholar,4Dummer P.D. Limou S. Rosenberg A.Z. et al.APOL1 kidney disease risk variants: an evolving landscape.Semin Nephrol. 2015; 35: 222-236https://doi.org/10.1016/j.semnephrol.2015.04.008Google Scholar These variants are found almost exclusively in people with African, particularly West African and sub-Saharan, ancestry, in whom they may protect against a potentially fatal parasitic infection.5Freedman B.I. Limou S. Ma L. Kopp J.B. APOL1-associated nephropathy: a key contributor to racial disparities in CKD.Am J Kidney Dis. 2018; 72: S8-S16https://doi.org/10.1053/j.ajkd.2018.06.020Google Scholar Approximately 13% of the US Black population has 2 risk variants, though rates vary by ancestral region.5Freedman B.I. Limou S. Ma L. Kopp J.B. APOL1-associated nephropathy: a key contributor to racial disparities in CKD.Am J Kidney Dis. 2018; 72: S8-S16https://doi.org/10.1053/j.ajkd.2018.06.020Google Scholar,6Kramer H.J. Stilp A.M. Laurie C.C. et al.African ancestry–specific alleles and kidney disease risk in Hispanics/Latinos.J Am Soc Nephrol. 2017; 28: 915-922https://doi.org/10.1681/ASN.2016030357Google Scholar Relying on socially constructed racial categories raises numerous problems. In the absence of an alternative for rapidly assessing donors' likely continental ancestry, APOLLO relies on donor race as an imperfect proxy to identify individuals more likely to have risk variants. APOLLO's primary aim is to assess the effects of deceased kidney donors' APOL1 genotype on recipient outcomes. Secondarily, it aims to determine the effects of living donors' APOL1 genotype on their own health outcomes after kidney donation as well as recipient outcomes. As an observational cohort study, APOLLO poses minimal physical risks to participants, only involving collection of blood and sometimes urine from donors and their recipients.1Freedman B.I. Moxey-Mims M. The APOL1 long-term kidney transplantation outcomes network—APOLLO.Clin J Am Soc Nephrol. 2018; 13: 940-942https://doi.org/10.2215/CJN.01510218Google Scholar The history of abuse and racism in research and ongoing racial health inequities create distrust among many Black people toward research and researchers.7Corbie-Smith G. Thomas S.B. St George D.M. Distrust, race, and research.Arch Intern Med. 2002; 162: 2458-2463https://doi.org/10.1001/archinte.162.21.2458Google Scholar, 8Bussey-Jones J. Garrett J. Henderson G. Moloney M. Blumenthal C. Corbie-Smith G. The role of race and trust in tissue/blood donation for genetic research.Genet Med. 2010; 12: 116-121https://doi.org/10.1097/GIM.0b013e3181cd6689Google Scholar, 9Gordon E.J. Wicklund C. Lee J. Sharp R.R. Friedewald J. A national survey of transplant surgeons and nephrologists on implementing apolipoprotein L1 (APOL1) genetic testing into clinical practice.Prog Transplant. 2019; 29: 26-35https://doi.org/10.1177/1526924818817048Google Scholar The CAC aims to protect and advance the interests of Black people involved in APOLLO and to maximize the likelihood that research results will benefit Black people. The CAC comprises individuals who have received a kidney transplant, have chronic kidney disease (CKD), have donated a kidney, or have relatives with CKD and who identify as Black or African American. Two research team members participate in and help to coordinate CAC activities (ASI and JMD). The CAC participates fully in the biannual meetings of investigators and study coordinators, and holds monthly conference calls. Investigators proposing ancillary studies consult the CAC. Members of the CAC have access to the internal study website, which includes all study documents but not participant-level data. The CAC has a representative (NMJ) on the steering committee, which consists of the principal investigators from the 13 APOLLO clinical centers and coordinating center as well as representatives from the NIH, the United Network for Organ Sharing, and the Association of Organ Procurement Organizations, and also has representatives on several study subcommittees. The importance of transparency to build and maintain trust permeates CAC discussions and informs its recommendations. The CAC impresses upon investigators that many people distrust research when their lives and health care experiences have been affected by racism: mistrust does not just arise from historical events such as the US Public Health Service Syphilis Study at Tuskegee. Investigators must earn and maintain trust. Even though APOLLO poses fairly minimal risks and does not involve experimentation on participants, transparency is paramount. We describe 2 areas where the CAC's understanding of transparency shaped APOLLO. Laws, regulations, and institutional review boards (IRBs) sometimes allow practices that the CAC believes lack transparency. The CAC called on investigators to provide additional information and developed publicly available infographics to support education and transparency. Based on CAC recommendations, all participants and the legally authorized representatives of deceased donors may request their APOL1 research genetic test results. All genetic testing is done in a CLIA-certified laboratory to facilitate this. The CAC's concerns about transparency also had implications for living donor recruitment. During preliminary discussions, a small number of investigators suggested sharing information about APOLLO and recruiting living donors shortly after kidney donation. The APOLLO steering committee and the CAC felt this was unacceptable. The CAC was concerned that for some living donors the APOLLO recruitment might be their first opportunity to learn about APOL1 variants. Not all transplant programs routinely discuss APOL1 with potential living donors.9Gordon E.J. Wicklund C. Lee J. Sharp R.R. Friedewald J. A national survey of transplant surgeons and nephrologists on implementing apolipoprotein L1 (APOL1) genetic testing into clinical practice.Prog Transplant. 2019; 29: 26-35https://doi.org/10.1177/1526924818817048Google Scholar, 10McIntosh T. Mohan S. Sawinski D. Iltis A. DuBois J.M. Variation of ApoL1 testing practices for living kidney donors.Prog Transplant. 2020; 30: 22-28https://doi.org/10.1177/1526924819892917Google Scholar, 11Umeukeje E.M. Young B.A. Fullerton S.M. et al.You are just now telling us about this? African American perspectives of testing for genetic susceptibility to kidney disease.J Am Soc Nephrol. 2019; 30: 526-530https://doi.org/10.1681/ASN.2018111091Google Scholar The CAC believes that all potential living donors should have information about APOL1 far enough in advance of donation to learn more about APOL1 risk factors and make decisions—a view many African Americans share.11Umeukeje E.M. Young B.A. Fullerton S.M. et al.You are just now telling us about this? African American perspectives of testing for genetic susceptibility to kidney disease.J Am Soc Nephrol. 2019; 30: 526-530https://doi.org/10.1681/ASN.2018111091Google Scholar, 12Gordon E.J. Amórtegui D. Blancas I. Wicklund C. Friedewald J. Sharp R.R. A focus group study on African American living donors' treatment preferences, sociocultural factors, and health beliefs about apolipoprotein L1 genetic testing.Prog Transplant. 2019; 29: 239-247https://doi.org/10.1177/1526924819854485Google Scholar, 13Gordon E.J. Amόrtegui D. Blancas I. Wicklund C. Friedewald J. Sharp R.R. African American living donors' attitudes about APOL1 genetic testing: a mixed methods study.Am J Kidney Dis. 2018; 72: 819-833https://doi.org/10.1053/j.ajkd.2018.07.017Google Scholar, 14Berrigan M. Austrie J. Fleishman A. et al.Opinions of African American adults about the use of apolipoprotein L1 (ApoL1) genetic testing in living kidney donation and transplantation.Am J Transplant. 2021; 21: 1197-1205https://doi.org/10.1111/ajt.16206Google Scholar Even though living donors make donation decisions independent of APOLLO and APOLLO would not alter their care, the CAC recommended that all living donors receive information about APOLLO or APOL1 testing at least 1 month before donor nephrectomy. The CAC and steering committee agreed to a 2-week minimum to align with clinical realities (the CAC was consulted regarding additional adjustments during the COVID-19 pandemic). The CAC had 3 primary reasons for requiring advance notice: 1. Learning about APOL1 too close to the time of or after donation could cause psychosocial harms. Living donors might be upset they were not given this information earlier and might worry about their own or their recipient's health. 2. Learning about APOL1 after donation might undermine donor trust if they felt they should have received information earlier. This could make them less likely to participate in APOLLO, undermining the study, and could harm their relationship with their transplant physicians. 3. Investigators should not be complicit with, or appear to support, withholding information potential living donors deserve. The CAC requested verifiable documentation of the advance disclosure of APOL1 information, given that biomedical research in the United States is situated in a history of racist policies and practices. Critically, APOLLO investigators never proposed withholding information about APOL1 from potential living donors; rather, the CAC's transparency concern involved clinical practices that were not under APOLLO investigators' control. Although research and clinical practice may be distinct for regulatory purposes, patients and potential participants might experience them as connected in ways that have significant implications for the ethical conduct of research. APOLLO's mission is "to improve the lives of those who donate or receive a kidney by learning more about genetic variations . . . found among some people of African descent."15APOLLOBackground of APOLLO. May 2020.https://theapollonetwork.org/opo_hla_videos.cfmGoogle Scholar It is vital to communicate this message—and especially the potential benefits—to the Black community, to potential participants, and to families making organ donation decisions. The CAC found investigators would often speak about APOLLO's benefits in terms of gaining scientific knowledge. As an observational study, APOLLO offers participants no direct potential clinical benefits. Further, IRBs often prohibit investigators from making statements that sound like promises of benefit. In contrast, the CAC felt that the investigators needed to clearly articulate how this study was designed and intended to benefit Black patients in the future. Black people face significantly higher rates of kidney disease, are less likely to receive kidney transplants, and are more likely to experience graft failure than European Americans.16Johansen K.L. Chertow G.M. Foley R.N. et al.US Renal Data System 2020 annual data report: epidemiology of kidney disease in the United States.Am J Kidney Dis. 2021; 77: A7-A8https://doi.org/10.1053/j.ajkd.2021.01.002Google Scholar,17Shah S. Shapiro R. Murphy B. Menon M.C. APOL1 high-risk genotypes and renal transplantation.Clin Transplant. 2019; 33e13582https://doi.org/10.1111/ctr.13582Google Scholar The Kidney Donor Risk Index (KDRI) is a quality indicator used in allocating deceased donor kidneys to recipients. It includes self-reported donor race and treats Black donor race as indicative of poorer organ quality because, on average, kidney transplants from Black donors fail earlier than transplants from non-Black donors. The KDRI contributes to many kidneys from Black donors being discarded rather than transplanted.1Freedman B.I. Moxey-Mims M. The APOL1 long-term kidney transplantation outcomes network—APOLLO.Clin J Am Soc Nephrol. 2018; 13: 940-942https://doi.org/10.2215/CJN.01510218Google Scholar If APOLLO reveals that APOL1 genotype accounts for a significant portion of these earlier allograft failures, genotype could replace race in the KDRI, potentially reducing the number of kidneys that are discarded and eliminating the problematic reliance on race in kidney discard policies.1Freedman B.I. Moxey-Mims M. The APOL1 long-term kidney transplantation outcomes network—APOLLO.Clin J Am Soc Nephrol. 2018; 13: 940-942https://doi.org/10.2215/CJN.01510218Google Scholar,18Hardimon M.O. Race concepts in medicine.J Med Philos. 2013; 38: 6-31https://doi.org/10.1093/jmp/jhs059Google Scholar Black living kidney donors experience worse health outcomes after donation than European Americans.19Muzaale A.D. Massie A.B. Wang M.C. et al.Risk of end-stage renal disease following live kidney donation.JAMA. 2014; 311: 579-586https://doi.org/10.1001/jama.2013.285141Google Scholar,20Lentine K.L. Schnitzler M.A. Xiao H. et al.Consistency of racial variation in medical outcomes among publicly and privately insured living kidney donors.Transplantation. 2014; 97: 316-324https://doi.org/10.1097/01.TP.0000436731.23554.5eGoogle Scholar If APOLLO's findings contribute to our understanding of who is actually at heightened risk from donating a kidney, more people might be willing to donate. This could help reduce the existing disparity in access to living donor kidney transplants.21Newell K.A. Formica R.N. Gill J.S. et al.Integrating APOL 1 gene variants into renal transplantation: considerations arising from the American Society of Transplantation Expert Conference.Am J Transplant. 2017; 17: 901-911https://doi.org/10.1111/ajt.14173Google Scholar,22Mohan S. Iltis A.S. Sawinski D. DuBois J.M. APOL1 genetic testing in living kidney transplant donors.Am J Kidney Dis. 2019; 74: 538-543https://doi.org/10.1053/j.ajkd.2019.02.007Google Scholar Above all, understanding the relationship between APOL1 risk variants and kidney health may empower people to make wise health choices and informed decisions. The CAC's guidance to APOLLO researchers has been motivated by challenging common research assumptions (Table 1). The APOLLO research team has been open to hearing these and has relied on CAC guidance to navigate these assumptions. The CAC has promoted respect for participants, minimized the risk of harm, and helped foster trust.2Kimmel P.L. Jefferson N. Norton J.M. Star R.A. How community engagement is enhancing NIDDK research.Clin J Am Soc Nephrol. 2019; 14: 768-770https://doi.org/10.2215/CJN.14591218Google Scholar Relying on the CAC's guidance also may improve research recruitment and ultimately the ability to obtain valuable, generalizable knowledge from the APOLLO study.Table 1CAC Revisions to Common Research AssumptionsCommon Research AssumptionsCAC RevisionsIt is sufficient to comply with research regulations and IRB requirements.Given past and current experiences of racism, earning the trust of participants may require more information than research regulations and IRBs require.In a clinical observational study, it is crucial to separate the research component from the clinical care component.Participants may not view the clinical and research components as separate. Researchers may need to share additional information and avoid any connection with clinical practices that lack or appear to lack transparency.An observational study will not offer direct benefits. It is unethical to promise downstream benefits to participants or say too much about possible future benefits.It is essential to articulate how a study that does not offer participants direct benefit is meant to benefit the community as a whole, especially disadvantaged communities. For APOLLO, the benefit to the Black community must be clearly described.Abbreviations: APOLLO: APOL1 Long-Term Kidney Transplantation Outcomes; CAC, Community Advisory Council; IRB, institutional review board. Open table in a new tab
Referência(s)