Ethical and Sociocultural Implications of Genetic Testing in Transplantation

移植中基因检测的伦理和社会文化意义

• 批准号: 9295961
• 负责人: Elisa J Gordon
• 金额: $ 7.83万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-14 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9295961
• 关键词: Affect; African American; Alleles; American; Apolipoproteins; Attitude; Awareness; Charge; Chronic Kidney Failure; Clinical; Communities; Counseling; Data; Development; Diabetes Mellitus; Dialysis procedure; Disease; Donor person; Education; Educational Materials; Eligibility Determination; End stage renal failure; Equipoise; Ethics; European; Evaluation; Focus Groups; Fostering; Frequencies; Future; Genetic; Genetic Counseling; Genetic Materials; Genetic Research; Genetic Screening; Genetic screening method; Genetic study; Genomics; Graft Survival; Guidelines; Health Knowledge, Attitudes, Practice; Informed Consent; Interview; Kidney; Kidney Failure; Kidney Transplantation; Learning; Living Donors; Medical; Modeling; National Human Genome Research Institute; Nephrology; Nonmaleficence; Organ; Organ Donor; Outcome; Patients; Physicians; Polycystic Kidney Diseases; Population; Precision Medicine Initiative; Provider; Qualitative Methods; Quality of life; Relative Risks; Renal function; Reporting; Research; Risk; Safety; Shapes; Site; Structure; Surveys; Testing; Time; Transplantation; United States National Institutes of Health; Variant; base; case-by-case basis; clinical practice; disparity reduction; epidemiology study; expectation; genetic variant; improved; longitudinal analysis; preference; premature; prevent; research clinical testing; research study; screening; treatment choice; uptake; willingness

PROJECT SUMMARY/ABSTRACT Living donor kidney transplantation (LDKT) is promoted to redress the shortage of kidneys for transplantation. However, studies show that living donors (LDs) have a greater risk of kidney failure than healthy non-LDs post-donation.4-6 Moreover, African American (AA) LDs have an even greater risk of kidney failure post-donation than European American (EA) LDs.4,5 These findings have generated heightened concerns in the transplant community over protecting LDs' safety and improving LDs' informed consent.7-14 Genetics may help explain this disparity. Genetics research found that Apolipoprotein L1 (APOL1) gene variants (1-2 alleles) are significantly associated with kidney failure predominantly in AAs.15-19 Kidney transplants from deceased donors with APOL1 variants had significantly shorter survival than kidneys from donors without variants.20 APOL1 variants may explain why AA LDs have a greater risk of kidney failure post- donation than do EA LDs.5,6,20 Thus, testing AA potential LDs for APOL1 variants could better risk stratify them. Little is known about the transplant community's attitudes about and practices of integrating APOL1 genetic testing into the routine clinical evaluation of AA LDs. No guidelines exist for genetic testing in transplantation. While proponents believe that the evidence is strong enough to warrant APOL1 testing,21,22 critics counter that testing is premature.23 Yet some transplant centers are using APOL1 testing routinely,22 or on a case-by-case basis. Transplant centers' practices are ethically charged: (not) using APOL1 testing could harm AA LDs. LDs unknowingly with the variants might make less informed decisions and unnecessarily undergo donation, which would violate the ethical principle of non-maleficence, as LDs gain no direct medical benefit from donation.25-27 Conversely, by learning they had APOL1 variants, LDs may choose to not donate to protect themselves or prevent the recipient from getting a kidney with potentially lower graft survival. Testing may also affect AAs' cultural identity, which in turn could shape attitudes about LDs' willingness to use APOL1 testing. The objective of this study is to assess the ethical and sociocultural implications of physicians' use of APOL1 testing for AA LDs, and to develop culturally sensitive educational materials for genetic counseling about APOL1 testing. We will assess the transplant community's normative expectations, attitudes, and current practices about testing AA potential LDs for APOL1 variants through a national survey. We will also assess AA LDs' information preferences, attitudes about, and willingness to be tested for APOL1 variants through semi-structured interviews. The results will inform the development of culturally sensitive education materials for genetic counseling about APOL1 testing, which will be refined by focus groups with AA LDs. The proposed study is timely because APOL1 testing could increase AA potential LDs' safety and reduce disparities in AA LD outcomes. This study facilitates NHGRI's initiative to better understand the implementation of emerging clinical genomics into clinical practice,32 consistent with the NIH's precision medicine's initiative.33

项目概要/摘要 推广活体肾移植（LDKT）以解决肾脏短缺问题 移植。然而，研究表明，活体捐献者（LD）患肾衰竭的风险比 捐赠后健康的非 LD 患者。4-6 此外，非洲裔美国人 (AA) LD 患者患肾病的风险更大 与欧洲美国 (EA) LD 相比，捐赠后失败。4,5 这些发现引起了高度关注 移植界对保护 LD 安全和改善 LD 知情同意的担忧7-14 遗传学可能有助于解释这种差异。遗传学研究发现载脂蛋白L1（APOL1）基因 变异（1-2 个等位基因）与主要在 AA 中的肾衰竭显着相关。15-19 肾 来自带有 APOL1 变异的已故捐献者的移植肾的存活率明显低于来自 20 APOL1 变异可以解释为什么 AA LD 术后肾衰竭风险更大 捐赠比 EA LD 更好。5,6,20 因此，测试 AA 潜在 LD 的 APOL1 变体可以更好地对它们进行风险分层。 关于移植界对整合 APOL1 基因的态度和实践知之甚少 测试进入 AA LD 的常规临床评估。移植中的基因检测尚无指南。 虽然支持者认为证据足够有力，足以保证进行 APOL1 测试，21,22 批评者反驳说 测试还为时过早。23 然而，一些移植中心正在常规使用 APOL1 测试，22 或根据具体情况进行测试 基础。移植中心的做法受到道德指控：（不）使用 APOL1 测试可能会损害 AA LD。 LD 不知不觉中携带变异的人可能会做出不明智的决定并不必要地接受捐赠，这 会违反非恶意的道德原则，因为 LD 不会从捐赠中获得直接的医疗利益。25-27 相反，通过得知他们有 APOL1 变体，LD 可能会选择不捐赠以保护自己或 防止受者获得移植物存活率可能较低的肾脏。测试也可能影响 AA 文化认同，这反过来又可能影响 LD 是否愿意使用 APOL1 测试。 本研究的目的是评估医生使用药物的伦理和社会文化影响 AA LD 的 APOL1 测试，并开发具有文化敏感性的遗传教育材料 有关 APOL1 测试的咨询。我们将评估移植界的规范期望， 通过全国调查测试 AA 潜在 LD 是否存在 APOL1 变体的态度和当前做法。 我们还将评估 AA LD 的信息偏好、态度以及接受 APOL1 测试的意愿 通过半结构化访谈的变体。结果将为文化敏感的发展提供信息 有关 APOL1 测试的遗传咨询教育材料，将由 AA 焦点小组完善 LD。拟议的研究是及时的，因为 APOL1 测试可以提高 AA 潜在 LD 的安全性并减少 AA LD 结果的差异。这项研究有助于 NHGRI 更好地了解实施情况 将新兴临床基因组学引入临床实践，32 与 NIH 的精准医学倡议一致。 33