Wake Forest APOLLO Scientific and Data Research Center

维克森林阿波罗科学与数据研究中心

• 批准号: 9975002
• 负责人: DONALD W BOWDEN
• 金额: $ 5万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-25 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9975002
• 关键词: APOL1 gene; Acute; Adult; African; African American; Allografting; American; Ancillary Study; Antibodies; Apolipoproteins; Archives; Area; Biological; Biometry; Characteristics; Childhood; Clinical; Clinical Data; Cohort Studies; Collection; Communication; Country; Creatinine; DNA; Data; Data Analyses; Data Security; Development; End stage renal failure; Ensure; Ethicists; Ethics; Ethnic group; European; Evaluation; Failure; Funding; Genes; Genetic; Genotype; Glomerular Filtration Rate; Health; Health Care Costs; Histologic; Human Resources; Informed Consent; Kidney; Kidney Transplantation; Laboratories; Lead; Leadership; Link; Living Donors; Manuals; Monitor; Multicenter Studies; National Institute of Diabetes and Digestive and Kidney Diseases; Nephrology; Online Systems; Operative Surgical Procedures; Organ; Organ Procurements; Outcome; Patients; Physicians; Population; Predisposition; Preparation; Procedures; Process; Prospective Studies; Proteinuria; Protocols documentation; Quality of life; Race; Renal function; Reporting; Request for Applications; Research; Research Personnel; Resources; Retrospective Studies; Risk; Risk Estimate; Safety; Sampling; Serum; Sickle Hemoglobin; Specimen; Statistical Data Interpretation; Structure; System; Time; Transplant Recipients; Transplantation; United Network for Organ Sharing; United States National Institutes of Health; Variant; Virus Diseases; Vital Status; base; biobank; clinical center; data quality; design; ethnic disparity; forest; genetic information; improved; improved outcome; indexing; kidney allograft; living kidney donor; non-diabetic; organ allocation; post-transplant; precision medicine; primary outcome; programs; prospective; racial and ethnic; racial disparity; repository; response; risk variant; screening; skills; tool; web site

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.

NIH APOL1 长期移植结果网络 (APOLLO) 协作 U01 将执行一项 对所有美国肾移植中供体和受体 APOL1 肾脏风险变异的全国前瞻性评估 来自非裔美国肾脏捐赠者的研究，以确定其对移植结果的影响。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。我们是 申请成为本 NIH 资助公告的 APOLLO 科学与数据研究中心 (SDRC)。 观察到来自已故非裔美国肾脏捐献者的移植肾同种异体移植存活期较短， 相对于已故的欧洲裔美国肾脏捐赠者。造成这种情况的原因尚不清楚，但可以回顾一下 报告表明，肾脏捐献者中存在两种载脂蛋白 L1 基因 (APOL1) 肾脏风险变异可能 助长了差距。这些变异在具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/族裔群体。 APOL1 基因型数据可以提供更准确的可能性评估 供体肾脏的长期同种异体移植肾功能，从而改善供体肾脏与移植肾的匹配 潜在的接受者，以优化肾同种异体移植物和患者的生存。这些信息可能会更好地告知 医生在做出分配决定之前了解器官质量以及生活安全 肾脏捐赠。在将这些基因型数据用于临床之前，需要进行一项前瞻性全国研究 评估非裔美国肾脏捐赠者和接受者的所有肾移植结果 基于 APOL1 基因型。需要收集回顾性研究中缺乏的信息，包括 受者 APOL1 基因型、同种异体移植失败的肾组织学数据以及 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、协助准备最终结果 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 临床和结果数据，进行基因分型、统计分析、主要结果“时间”的评估 基于供体 APOL1 基因型，非裔美国供体移植肾脏的同种异体移植失败” 并创建一个生物存储库。我们将纵向评估生命状态、肾功能和蛋白尿 基于 APOL1 基因型的非裔美国肾脏捐赠者。肾脏影响的前瞻性评估 供体 APOL1 基因型对血清肌酐浓度、估计肾小球滤过率和 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。结果有潜力 改变肾移植中的器官分配和知情同意流程，优化肾移植 提高同种异体移植存活率，减少优质肾脏的废弃，保护活体肾捐献者的健康。