Wake Forest APOLLO Scientific and Data Research Center

NIH APOL 1长期移植结果网络（APOLLO）协作U 01将执行一项 美国所有肾移植患者中供者和受者APOL 1肾风险变异的国家前瞻性评价 从非裔美国人的肾脏捐赠者，以确定他们对移植结果的影响。此外，后- 将评估非裔美国人活体肾脏捐赠者的捐赠健康和肾功能。我们 申请成为APOLLO科学和数据研究中心（SDRC）的NIH资助公告。 从死亡的非裔美国人肾脏供体的移植中观察到肾移植存活率较短， 相对于已故的欧洲裔美国人肾脏捐赠者。原因不明，但可以追溯 有报道表明，在肾脏捐赠者中存在两种载脂蛋白L1基因（APOL 1）肾脏风险变异体， 造成了差距。这些变异在最近有非洲血统的人群中很常见（如 非裔美国人），在那里他们与非糖尿病终末期肾病密切相关，但在美国罕见。 其他种族/民族。APOL 1基因型数据可以提供更准确的评估可能性， 供肾的长期肾移植功能，从而改善供肾与 潜在的受体，以优化肾移植和患者生存。这些信息可以更好地告知 在作出分配决定之前，医生对器官质量和生活安全的了解 肾脏捐赠在这些基因型数据可以用于临床之前，需要进行一项前瞻性的国家研究， 评估非裔美国人供体和肾脏受体的所有肾移植结果 基于APOL 1基因型。需要收集回顾性研究缺乏的信息，包括 受体APOL 1基因型、移植失败的肾组织学数据和BK病毒的存在或发展 感染、供体特异性抗体和肾移植后的急性排斥反应。我们将执行 APOLLO网络的以下活动：总体研究协调，协助编写最后报告， 方案和程序手册，开发数据跟踪工具和研究网站，收集和存档 临床和结局数据，进行基因分型，统计分析，评估主要结局“时间 基于供体APOL 1基因型， 建立一个生物储存库我们将在生活中纵向评估生命状态、肾功能和蛋白尿 基于APOL 1基因型的非裔美国人肾脏供体。肾脏影响的前瞻性评估 供体APOL 1基因型对血清肌酐浓度、估计的肾小球滤过率和 还将对具有功能性同种异体移植物的移植受者进行蛋白尿检查。结果有可能 改革肾移植中的器官分配和知情同意程序，优化肾移植的 提高同种异体移植物存活率，减少优质肾脏的丢弃，并保护活体肾脏供体的健康。

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 US kidney transplants from African American kidney donors to determine their effect on transplant outcomes. In addition, the post- donation health and kidney function of African American living kidney donors will be assessed. We are applying to be the APOLLO Scientific and Data Research Center (SDRC) for this NIH Funding Announcement. Shorter renal allograft survival is observed for transplantations from deceased African American kidney donors, relative to deceased European American kidney donors. Reasons for this are unknown, but retrospective reports suggest that presence of two apolipoprotein L1 gene (APOL1) renal-risk variants in kidney donors may contribute to the disparity. These 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, but rare in other racial/ethnic groups. APOL1 genotype data 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 in order to optimize renal allograft and patient survival. This information may better inform physicians about organ quality prior to decisions on allocation are made and regarding the safety of living kidney donation. Before this genotypic data can be used clinically, a prospective national study is required to evaluate all kidney transplantation outcomes from African American donors and recipients of their kidneys based on APOL1 genotypes. Information lacking from retrospective studies needs to be collected, including recipient APOL1 genotypes, renal histologic data in failed allografts and presence or development of BK viral infections, donor specific antibodies, and acute rejections after kidney transplantation. We will perform the following activities for the APOLLO Network: overall study coordination, assist with preparation of the final protocol and Manual of Procedures, develop data tracking tools and the study website, collect and archive clinical and outcomes data, perform genotyping, statistical analyses, assessment of the primary outcome “time to allograft failure in transplanted kidneys from African American donors, based on donor APOL1 genotypes” and create a bio-repository. We will longitudinally assess vital status, kidney function and proteinuria in living African American kidney donors based on APOL1 genotypes. Prospective assessment of the effects of kidney donor APOL1 genotypes on serum creatinine concentration, estimated glomerular filtration rate, and proteinuria in transplant recipients with functioning allografts will also be performed. 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.