Ethical and Sociocultural Implications of Genetic Testing in Transplantation

项目概要/摘要 活体供肾移植（LDKT）被推广，以解决肾脏短缺的问题， 移植然而，研究表明，活体供者（LD）患肾衰竭的风险高于 4-6此外，非裔美国人（AA）LD的肾脏损害风险更大， 失败后捐赠比欧洲美国（EA）LD。4，5这些发现产生了提高 移植界对保护LD的安全和改善LD的知情同意的关注。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（APOL 1）基因 变异（1-2个等位基因）与主要在AA中的肾衰竭显著相关。15 -19肾 来自携带APOL 1变异体的已故供体的移植物的存活率显著低于来自 20 APOL 1变异体可能解释了为什么AA LD在移植后发生肾衰竭的风险更大。 5，6，20因此，检测AA潜在LD的APOL 1变体可以更好地对它们进行风险分层。 移植界对整合APOL 1基因的态度和做法知之甚少。 纳入AA LD的常规临床评价。没有关于移植中基因检测的指导方针。 虽然支持者认为证据足够有力，足以证明APOL 1测试，但批评者反驳说， 23然而，一些移植中心正在常规使用APOL 1检测，22或根据具体情况进行检测。 基础移植中心的做法在道德上受到指控：（不）使用APOL 1测试可能会伤害AA LD。LDS 在不知情的情况下，变异可能会做出不太明智的决定，并不必要地接受捐赠， 将违反不伤害的伦理原则，因为LD不会从捐赠中获得直接的医疗利益。 相反，通过了解他们有APOL 1变体，LD可能会选择不捐赠以保护自己， 防止接受者获得移植存活率可能较低的肾脏。测试也可能影响AA的 文化身份，这反过来又会影响LD是否愿意使用APOL 1测试。 本研究的目的是评估医生使用的道德和社会文化的影响 对AA LD进行APOL 1检测，并为遗传学制定文化敏感的教育材料， 关于APOL 1检测的问题我们将评估移植界的标准期望， 态度，以及通过全国调查检测AA潜在LD的APOL 1变异的现行做法。 我们也会评估AA LD的信息偏好，态度，并愿意接受APOL测试1 通过半结构化的面试。研究结果将有助于发展对文化敏感的 关于APOL 1检测的遗传咨询教育材料，将由AA焦点小组进行完善 身份证拟议的研究是及时的，因为APOL 1检测可以增加AA潜在LD的安全性， AA LD结果的差异。这项研究有助于NHGRI的倡议，以更好地了解实施 新兴临床基因组学进入临床实践，32与NIH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