Wake Forest Collaborative Application for an APOLLO Clinical Center

我们正在申请作为 APOLLO 临床中心参与这项全国性前瞻性研究。美国国立卫生研究院 APOL1 长期移植结果网络 (APOLLO) 合作组织 U01 将进行全国性移植手术 对美国所有肾移植中供体和受体 APOL1 肾脏风险变异的前瞻性评估 非裔美国捐赠者确定其对移植结果的影响。另外，生活健康 非裔美国肾脏捐赠者将接受评估。先前回顾性研究中缺乏的信息 需要收集，包括同种异体移植失败的肾脏组织学数据以及 BK 的存在或发展 病毒感染、供体特异性抗体和肾移植后的急性排斥反应。我们的调查 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，以解决显着的问题 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 美国肾脏捐赠者的寿命不如已故欧洲裔美国人肾脏捐赠者的寿命 捐助者。其原因尚不清楚，但回顾性报告表明，两种载脂蛋白的存在 肾脏捐赠者的 L1 (APOL1) 基因肾脏风险变异可能有所贡献。这些肾脏风险变异常见于 具有近代非洲血统的人群（例如非洲裔美国人），他们与非洲人密切相关 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。美国POL1 基因型数据可能被证明在临床上对最近有非洲血统的人在分配方面有用 用于移植的死亡供体肾脏和对未来活体肾脏供体的评估。基因型 信息（精准医学）可以更准确地评估长期肾病的可能性 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生存。信息可以更好地让医生事先了解器官质量 分配决定。然而，在这些基因型数据用于临床之前， 需要前瞻性全国研究来评估非裔美国人的肾移植结果 基于 APOL1 基因型的肾脏捐赠者和接受者。先前回顾中缺乏信息 将收集研究，包括同种异体移植失败的肾脏组织学数据以及 BK 的存在或发展 病毒感染、供体特异性抗体和肾移植后的急性排斥反应。这就是道理 以及当前 APOLLO 试验的设置。在这项重要的多站点研究中，我们的站点将与 阿波罗科学与数据研究中心及其他参与站点招募和前瞻性 根据 APOLLO 协议跟踪符合条件的肾脏捐赠者和移植受者。结果有 改变肾移植器官分配和知情同意流程的潜力，优化 提高同种异体肾的成活率，减少优质肾的报废，保护活体肾的健康 捐助者。

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.