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

项目摘要/摘要 活着的供体肾脏移植（LDKT）被提升为纠正肾脏短缺 移植。但是，研究表明，活着的捐助者（LDS）的肾衰竭风险比 4-6此外，非裔美国人（AA）LDS的肾脏风险更大 失败后的失败比欧美（EA）LDS.4,5这些发现产生了增强 关于保护LDS的安全和改善LDS的知情同意书，移植社区的担忧。7-14 遗传学可能有助于解释这一差异。遗传学研究发现载脂蛋白L1（Apol1）基因 变体（1-2等位基因）主要与AAS中的肾衰竭显着相关。15-19肾脏 来自APOL1变体的已故捐赠者的移植物的生存率明显短于肾脏 没有变体的捐助者。20Apol1变体可以解释为什么AA LDS在 捐赠比ea lds.5,6,20因此，测试APOL1变体的AA潜在LDS可以更好地风险分层它们。 关于移植社区对整合apol1遗传的态度和实践知之甚少 测试AA LDS的常规临床评估。在移植中没有基因检测的指南。 支持者认为，证据足以保证APOL1测试，但有21,22名评论家反驳 测试还为时过早。23然而，一些移植中心通常使用APOL1测试，22或逐案 基础。在道德上，移植中心的做法是指控的：（不）使用APOL1测试可能会损害AA LDS。 LDS 在不知不觉中，随着变体可能会做出较少明智的决定和不必要的捐赠，这是 由于LDS不会从捐赠中获得直接医疗利益，因此违反了非遗憾的道德原则。25-27 相反，通过得知它们具有APOL1变体，LDS可能会选择不捐款以保护自己或 防止接受者获得具有潜在较低移植物存活率的肾脏。测试也可能影响AAS 文化身份反过来又可以影响对LDS使用APOL1测试意愿的态度。 这项研究的目的是评估医生使用的道德和社会文化含义 APOL1测试的AA LDS，并为遗传开发具有文化敏感的教育材料 有关APOL1测试的咨询。我们将评估移植社区的规范期望， 通过全国调查，对APOL1变体测试AA潜在LDS的态度和当前实践。 我们还将评估AA LDS的信息偏好，对APOL1进行测试的意愿 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测试的遗传咨询的教育材料，该材料将由与AA的焦点小组完善 LDS。拟议的研究是及时的，因为APOL1测试可以提高AA潜在的LDS安全性并降低 AA LD结果的差异。这项研究促进了NHGRI的主动性，以更好地了解实施 新兴的临床基因组学进入临床实践，32与NIH的Precision Mediciative一致。33