Ethical and Sociocultural Implications of Genetic Testing in Transplantation

项目摘要/摘要 推广活体供肾移植(LDKT)，以解决肾脏短缺的问题 移植。然而，研究表明，活体捐赠者(LD)患肾衰竭的风险比 4-6此外，非裔美国人(AA)LDS患肾脏的风险更大 失败后的捐赠比欧美(EA)的LD.4，5这些发现产生了更高的 移植社区对保护LDS的安全性和改善LDS的知情同意的担忧。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 突变(1-2个等位基因)与肾衰竭显著相关，主要发生在AAS。15-19肾 来自APOL1变异的已故供者的移植肾的存活时间明显短于来自 20个APOL1变异可以解释为什么AA LDS在移植后肾功能衰竭的风险更大。 5，6，20因此，测试AA潜在的LDs的APOL1变种可以更好地对它们进行风险分层。 移植团体对整合APOL1基因的态度和做法知之甚少 纳入再障腰椎病的常规临床评价。目前还没有关于移植中基因测试的指南。 虽然支持者认为证据足够有力，足以证明APOL1测试的合理性，但21，22名批评者则反驳说 检测还为时过早。23然而，一些移植中心正在常规使用APOL1检测，22或逐个进行检测 基础。移植中心的做法是合乎道德的：(不)使用APOL1检测可能会损害AA LDS。LDS 在不知情的情况下使用变种可能会做出不那么知情的决定，并不必要地接受捐赠，这 会违反无恶意的道德原则，因为LDS不会从捐赠中获得直接的医疗利益。 相反，通过了解到他们有APOL1变体，LDS可能会选择不捐赠来保护自己或 防止受者获得移植肾存活率可能较低的肾脏。检测也可能影响美国汽车协会 文化认同，这反过来又可能形成对学习障碍患者是否愿意使用APOL1测试的态度。 这项研究的目的是评估医生使用的伦理和社会文化影响。 对再生障碍性贫血进行载脂蛋白1检测，并开发对文化敏感的遗传学教育材料 关于APOL1测试的咨询。我们将评估移植社区的规范期望， 关于通过全国调查测试APOL1变体的AA潜在LDS的态度和当前做法。 我们还将评估AA LDS的信息偏好、对APOL1的态度和接受测试的意愿 通过半结构化访谈的变种。这一结果将为文化敏感性的发展提供信息。 关于载脂蛋白1检测的遗传咨询教育材料，将由AA焦点小组改进 LDS。建议的研究是及时的，因为APOL1检测可以增加AA潜在的LDS的安全性并降低 再生障碍性肝病结果的差异。这项研究有助于NHGRI主动更好地了解执行情况 将新兴的临床基因组学应用于临床实践，32与美国国立卫生研究院的精准医学倡议一致。

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