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: 9768568
• 负责人: BRUCE A JULIAN
• 金额: $ 34.61万
• 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 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9768568
• 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; 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; clinical implementation; 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.

从已故的非裔美国捐助者亲戚移植的肾脏观察到较短的同种异将存活率 来自已故欧美捐助者的人。最近的回顾性报告表明 肾脏供体中有两个载脂蛋白L1基因（Apol1）肾风险变体的存在明显 有助于这种差异。 APOL1肾风险变种在非洲血统的美国人口中很常见 （主要是非裔美国人），并且与非 - 糖尿病性肾脏疾病，但是这些风险变异在其他种族中很少见。在APOL1基因型数据之前 可以广泛应用于移植社区，但是，一项前瞻性多中心研究必须是 表演以评估非洲血统捐助者的肾脏结果。关键的临床移植物 需要收集先前的回顾性研究中缺少的信息，尤其是肾脏培训 数据和关键潜在修饰符，例如病毒感染的发展，供体特异性抗体和 急性排斥的发作。 NIH将资助全国前瞻性研究，以评估APOL1的影响 肾风险变体关于与非洲人的死者或活捐赠者的肾脏的结果 肾切除术后非洲血统的血统和肾脏健康。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 中心将从每个参与者那里收集一次性的血液样本，以在SDRC处进行APOL1基因分型，并将 向接收者和活捐赠者提交纵向临床数据，以评估SDRC的影响 APOL1基因型关于慢性肾脏疾病或末期肾脏疾病的发展。从中的结果 国家研究有可能改变器官分配和知情同意程序 从非洲血统的捐助者那里移植肾脏，改善同种异体移植生存，并提供 更好地理解Apol1肾风险变体的机制。