Wake Forest Collaborative Application for an APOLLO Clinical Center

我们申请以阿波罗临床中心的身份参加这项全国性的前瞻性研究。美国国立卫生研究院 APOL1长期移植成果网络(Apollo)Collaborative U01将表演全国性 在所有美国肾移植中对供受者APOL1肾脏风险变异的前瞻性评估 非洲裔美国人捐赠者以确定他们对移植结果的影响。此外，生活的健康 非洲裔美国人的肾脏捐赠者将接受评估。以前的回溯性研究所缺乏的信息 需要收集包括同种异体移植失败和BK的存在或发展的肾脏组织学数据 病毒感染、供者特异性抗体和肾移植后的急性排斥反应。我们的调查人员 由两名具有互补专业知识的PI领导的团队在临床试验中处于领先地位，以解决被标记的 患有终末期肾病的非裔美国人之间的差异。已故非洲人的肾移植 美国人的肾脏捐赠者的存活期没有来自欧洲的美国人的肾脏捐赠者长。 捐赠者。原因尚不清楚，但回顾报告表明，存在两种载脂蛋白 肾捐献者的L1(APOL1)基因肾脏风险变异可能起到一定作用。这些有肾脏风险的变种在 最近有非洲血统的人群(如非洲裔美国人)，在那里他们与 非糖尿病终末期肾病。相比之下，这些风险变异在其他种族群体中很少见。APOL1 在最近的非洲血统的分配设置中，基因型数据可能被证明是临床上有用的 用于移植的已故供者肾脏的评估和对潜在的活体肾脏捐赠者的评估。遗传型 信息(精确医学)可能对长期肾脏的可能性提供更准确的评估。 供体肾脏的同种异体移植功能，从而改善供体肾脏与潜在受体的匹配 优化同种异体肾移植和患者存活率。信息可能会更好地让医生了解器官质量 关于分配的决定。然而，在这些基因数据可以用于临床之前， 评估非裔美国人肾移植结果需要进行前瞻性的全国性研究 基于APOL1基因型别的肾脏供者和受者。以前的回顾中缺少的信息 将收集研究，包括移植失败的肾脏组织学数据和BK的存在或发展。 病毒感染、供者特异性抗体和肾移植后的急性排斥反应。这就是理由 为目前的阿波罗试验做准备。在这项重要的多站点研究中，我们的站点将与 阿波罗科学和数据研究中心和其他参与网站招聘并预期 根据阿波罗方案，关注符合条件的肾脏捐赠者和移植接受者。结果是 改变肾移植中器官分配和知情同意程序的潜力，优化 移植肾存活，减少优质肾脏的废弃，保护活体肾脏的健康 捐赠者。

We are applying to participate as an APOLLO Clinical Center in this national prospective study. The NIH APOL1 Long-term Transplantation Outcomes Network (APOLLO) Collaborative U01 will perform a national prospective evaluation of donor and recipient APOL1 renal-risk variants in all U.S. kidney transplantations from African American donors to determine their effects on transplant outcomes. In addition, the health of living African American kidney donors will be assessed. Information that was lacking from prior retrospective studies needs to be collected, including renal histologic data in allograft failures and presence or development of BK viral infections, donor specific antibodies, and acute rejections after kidney transplantation. Our investigative team, led by two PIs with complementary expertise, has led the way in clinical trials to address the marked disparities in African Americans with end-stage kidney disease. Renal transplantations from deceased African American kidney donors do not last as long as those from deceased European American kidney donors. Reasons for this are unknown, but retrospective reports suggest that presence of two apolipoprotein L1 (APOL1) gene renal-risk variants in kidney donors may contribute. These renal-risk variants are common in populations with recent African ancestry (such as African Americans), where they are strongly associated with non-diabetic end-stage kidney disease. In contrast, these risk variants are rare in other ethnic groups. APOL1 genotype data may prove to be clinically useful in those with recent African ancestry in the setting of allocation of deceased donor kidneys for transplantation and assessment of prospective living kidney donors. Genotypic information (precision medicine) may provide more accurate assessment of the likelihood for long-term renal allograft function in donor kidneys, thereby improving the matching of donor kidneys with potential recipients to optimize renal allograft and patient survival. Information may better inform physicians about organ quality prior to decisions on allocation. However, before these genotypic data can be used in the clinical setting, a prospective national study is required to evaluate kidney transplantation outcomes from African American donors and recipients of their kidneys based on APOL1 genotypes. Information lacking from prior retrospective studies will be collected, including renal histologic data in allograft failures and presence or development of BK viral infections, donor specific antibodies, and acute rejections after kidney transplantation. This is the rationale and setting for the current APOLLO trial. In this important multi-site study, our site will work closely with the APOLLO Scientific and Data Research Center and the other participating sites to recruit and prospectively follow eligible kidney donors and transplant recipients based on the APOLLO protocol. Results have the potential to transform the organ allocation and informed consent processes in kidney transplantation, optimize renal allograft survival, reduce the discard of good-quality kidneys, and protect the health of living kidney donors.