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

• 批准号: 9975831
• 负责人: BRUCE A JULIAN
• 金额: $ 13.33万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 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 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9975831
• 关键词: AIDS-Associated Nephropathy; Acute; Address; Adult; African; African American; Allografting; American; Antibodies; Apolipoproteins; Biopsy; Biopsy Specimen; Blood specimen; Chronic Kidney Failure; Clinical; Clinical Data; Communities; 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; 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; clinical center; clinical implementation; comorbidity; ethnic disparity; follow-up; genetic variant; improved; indexing; kidney allograft; kidney biopsy; non-diabetic; organ allocation; post-transplant; precision medicine; preservation; programs; prospective; rare variant; renal damage; risk variant; symposium

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.

从已故的非裔美国人供体亲属移植的肾脏观察到移植物存活时间较短 与已故的欧洲裔美国人捐献者的血液进行对比最近的回顾性报告表明， 两个载脂蛋白L1基因（APOL 1）肾脏风险变异体在肾脏供体中的存在显着 造成了这种差距。APOL 1肾脏风险变异在美国非洲血统人群中很常见 （主要是非洲裔美国人），并与非- 糖尿病肾病，但这些风险变异在其他种族群体中很少见。APOL 1基因型数据前 可以广泛应用于移植界，但是，必须进行前瞻性多中心研究， 用于评估来自非洲血统捐赠者的肾脏的结果。移植后危重临床 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，如病毒感染的发展，供体特异性抗体， 急性排斥反应发作。NIH将资助一项全国性的前瞻性研究，以评估APOL 1的影响。 非洲人已故或在世捐赠者肾脏接受者的肾脏风险变异结果 祖先和肾切除术后非洲血统的活体捐赠者的肾脏健康。这项研究将 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 研究中心将在SDRC采集每例受试者的一次性血液样本进行APOL 1基因分型，并将 向SDRC提交受者和活体捐赠者的纵向临床数据，以评估 APOL 1基因型对慢性肾脏疾病或终末期肾脏疾病发展的影响。由此产生的结果 国家研究有可能改变器官分配和知情同意过程， 移植来自非洲血统供体的肾脏，提高肾移植存活率，并提供 更好地了解APOL 1肾脏风险变异产生肾脏疾病的机制。