APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO) Clinical Center

APOL1 长期肾移植结果网络 (APOLLO) 临床中心

基本信息

批准号：
9439431
负责人：
BRUCE A JULIAN
金额：
$ 27.78万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
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 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9439431
关键词：
AIDS-Associated Nephropathy Acute Address Adult African African American Allografting American Antibodies Apolipoproteins Biological Preservation Biopsy Biopsy Specimen Blood specimen Chronic Kidney Failure Clinical Clinical Data Communities Comorbidity Creatinine Cytomegalovirus Infections DNA Data Development Documentation Donor person End stage renal failure Enrollment Ethnic group European Failure Focal Segmental Glomerulosclerosis Funding Generations Genes Genotype Health Histologic Histology Hypertension Immunosuppressive Agents Informed Consent Ischemia Kidney Kidney Diseases Kidney Transplantation Lesion Living Donors Lupus Nephritis Methods Modeling Multicenter Studies National Institute of Diabetes and Digestive and Kidney Diseases Nephrectomy Opportunistic Infections Outcome Participant Pathology Patients Persons Pharmaceutical Preparations Policies Population Process Prospective Studies Proteinuria Renal clearance function Renal function Reporting Research Research Personnel Retrospective Studies Risk Risk Assessment Sampling Serious Adverse Event Serum Societies Time Tissues Transplant Recipients Transplantation United States National Institutes of Health Urinary tract infection Variant Virus Diseases base biobank ethnic disparity follow-up genetic variant improved indexing kidney allograft non-diabetic organ allocation precision medicine programs prospective rare variant risk variant symposium

项目摘要

Shorter allograft survival is observed for kidneys transplanted from deceased African American donors relative to those from deceased European American donors. Recent retrospective reports have indicated that the presence of two apolipoprotein L1 gene (APOL1) renal-risk variants in the kidney donors significantly contributes to this disparity. APOL1 renal-risk variants are common in U.S. populations with African ancestry (primarily African Americans) and are strongly associated with end-stage renal disease for patients with non- diabetic kidney disease, yet these risk variants are rare in other ethnic groups. Before APOL1 genotypic data can be widely applied in the transplant community, however, a prospective multi-center study must be performed to evaluate outcomes of kidneys from donors with African ancestry. Critical clinical post-transplant information that was lacking in the prior retrospective studies needs to be collected, particularly kidney-biopsy data and key potential modifiers such as development of viral infections, donor-specific antibodies, and episodes of acute rejection. The NIH will fund a nationwide prospective study to assess the impact of APOL1 renal-risk variants on the outcomes of recipients of a kidney from a deceased or living donor with African ancestry and on the kidney health of living donors with African ancestry after nephrectomy. The study will consist of as many as 15 Clinical Centers and a central Scientific Data Research Center (SDRC). The Clinical Centers will collect one-time blood samples from each participant for APOL1 genotyping at the SDRC and will submit longitudinal clinical data for the recipients and living donors to the SDRC to assess the impact of APOL1 genotype on development of chronic kidney disease or end-stage renal disease. The results from this national study have the potential to transform organ allocation and informed consent processes in the transplantation of kidneys from donors with African ancestry, improve renal allograft survival, and provide a better understanding of the mechanisms whereby APOL1 renal-risk variants produce kidney disease.

观察到从已故非裔美国捐献者亲属移植的肾脏的同种异体移植物存活时间较短来自已故欧洲裔美国捐赠者的捐赠。最近的回顾性报告表明，肾脏捐赠者中存在两种载脂蛋白 L1 基因 (APOL1) 肾脏风险变异造成了这种差距。 APOL1 肾脏风险变异在非洲血统的美国人群中很常见（主要是非裔美国人）并且与非患有终末期肾病的患者密切相关糖尿病肾病，但这些风险变异在其他种族群体中很少见。 APOL1 基因型数据之前可以在移植界广泛应用，但是，必须进行前瞻性多中心研究旨在评估非洲血统捐赠者肾脏的结果。移植后关键临床需要收集先前回顾性研究中缺乏的信息，特别是肾活检数据和关键的潜在修饰因素，例如病毒感染、供体特异性抗体的发展，以及急性排斥反应发作。 NIH 将资助一项全国性前瞻性研究，以评估 APOL1 的影响非洲已故或活体捐赠者肾脏接受者结果的肾脏风险变异血统以及非洲血统活体捐赠者肾切除术后肾脏健康的影响。该研究将由多达 15 个临床中心和一个中央科学数据研究中心 (SDRC) 组成。临床各中心将从每位参与者那里采集一次性血液样本，以便在 SDRC 进行 APOL1 基因分型，并将向 SDRC 提交受赠者和活体捐赠者的纵向临床数据，以评估其影响 APOL1 基因型与慢性肾病或终末期肾病的发展有关。由此得出的结果国家研究有可能改变器官分配和知情同意程序移植非洲血统捐献者的肾脏，提高肾同种异体移植物的存活率，并提供更好地了解 APOL1 肾脏风险变异导致肾脏疾病的机制。