Wake Forest APOLLO Scientific and Data Research Center

维克森林阿波罗科学与数据研究中心

基本信息

批准号：
10475327
负责人：
DONALD W BOWDEN
金额：
$ 20.93万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-25 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10475327
关键词：
APOL1 gene Acute Adult African African American Allografting American Ancillary Study 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 donor-specific antibody 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

项目摘要

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长期移植成果网络（Apollo）协作U01将执行全国对捐赠者和接受者APOL1肾风险变体的预期评估从非裔美国人的肾脏供体来确定其对移植结果的影响。另外，邮政将评估非裔美国人活肾供体的捐赠健康和肾脏功能。我们是申请作为NIH资金公告的阿波罗科学和数据研究中心（SDRC）。观察到已故非裔美国肾脏供体移植的肾脏同种异体生存较短，重新质子是未知的，但是回顾性报道表明，肾脏供体中存在两个载脂蛋白L1基因（Apol1）肾风险变体可能对差异的贡献。这些变体在最近非洲血统的人群中很常见（例如非洲裔美国人），在那里他们与非糖尿病末期肾脏疾病密切相关，但很少见其他种族/族裔群体。 APOL1基因型数据可能会更准确地评估可能性的可能性供体肾脏中的长期肾脏同种异体移植功能，从而改善了供体肾脏的匹配潜在的接受者为了优化肾脏同种异体移植和患者生存。此信息可能会更好在决定分配之前，有关器官质量的医生进行了生命的安全性肾脏捐赠。在临床上使用此基因型数据之前，需要一项前瞻性国家研究评估非裔美国人捐助者和孩子的接受者的所有肾脏移植结果基于Apol1基因型。需要收集回顾性研究缺乏的信息，包括接受者APOL1基因型，失败合金中的肾脏组织学数据以及BK病毒的存在或开发肾移植后感染，供体特异性抗体和急性拒绝。我们将执行阿波罗网络的以下活动：整体研究协调，协助准备最终协议和手册，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，评估主要结果“时间基于供体APOL1基因型的非裔美国人捐助者移植儿童的同种异体移植失败” 并创建一个生物叛逆者。我们将纵向评估生活中的重要状态，肾功能和蛋白尿基于APOL1基因型的非裔美国肾脏供体。对肾脏影响的前瞻性评估供体APOL1基因型在血清肌氨酸浓度，估计的肾小球滤过率和还将进行具有功能同种异体移植的移植受者中的蛋白尿。结果有潜力要改变肾脏移植中的器官分配和知情同意过程，请优化肾脏同种异体移植的生存，减少质量儿童的丢弃，并保护活肾脏的捐助者的健康。