Wake Forest APOLLO Scientific and Data Research Center

NIH APOL1长期移植结果网络(Apollo)Collaborative U01将执行 全美肾移植中供受者APOL1肾脏风险变异的国家前瞻性评估 来自非裔美国人肾脏捐赠者，以确定他们对移植结果的影响。此外，邮局- 将评估非裔美国人活体肾脏捐赠者的捐赠健康和肾功能。我们是 申请成为阿波罗科学和数据研究中心(SDRC)，以宣布NIH的这笔资金。 观察到来自已故非裔美国人肾脏捐赠者的移植肾存活时间较短， 相对于已故的欧美肾脏捐赠者。原因不明，但可以追溯到 报告表明，肾捐赠者中存在两个载脂蛋白L1基因(APOL1)肾脏风险变异可能 造成这种差距的原因之一。这些变异在最近有非洲血统的人群中很常见(例如 非裔美国人)，他们与非糖尿病终末期肾病密切相关，但在 其他种族/民族群体。APOL1基因数据可能提供更准确的可能性评估 供体肾脏的长期移植功能，从而改善供体肾脏与 潜在的受者，以优化同种异体肾移植和患者存活率。这一信息可能会更好地告诉人们 医生在做出分配决定之前，会考虑器官质量，也会考虑到生活安全 肾脏捐献。在这种基因分型数据可以用于临床之前，需要进行一项前瞻性的全国性研究 评估非裔美国人肾脏捐赠者和受者的所有肾脏移植结果 基于APOL1基因型别。需要收集回溯性研究中缺乏的信息，包括 受体APOL1基因分型、移植失败的肾组织学资料和BK病毒的存在或发展 感染、供者特异性抗体和肾移植后的急性排斥反应。我们将表演 阿波罗网络的以下活动：总体研究协调，协助准备期末报告 程序规程和手册，开发数据跟踪工具和学习网站，收集和存档 临床和结果数据，执行基因分型，统计分析，评估主要结果 根据捐赠者的APOL1基因类型，非裔美国人捐赠者的移植肾移植失败 并创建一个生物信息库。我们将在生活中纵向评估生命状态、肾功能和蛋白尿 基于APOL1基因型别的非裔美国人肾脏捐赠者。肾脏影响的前瞻性评估 供者APOL1基因分型对血清肌酐浓度、估计肾小球滤过率的影响 同种异体移植物功能正常的移植受者的蛋白尿也将被进行。结果有可能 改变肾移植中的器官分配和知情同意程序，优化肾脏 移植肾存活，减少高质量肾脏的丢弃，并保护活体肾脏捐赠者的健康。

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.