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

长期肾移植结果网络 (APOLLO) 临床中心

• 批准号: 10731011
• 负责人: Kelly A Birdwell
• 金额: $ 33.3万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 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 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10731011
• 关键词: AIDS-Associated Nephropathy; Academic Medical Centers; Acceleration; Acute; Address; African American; African American population; African ancestry; Albumins; Allografting; American; Antibodies; Apolipoproteins; Bacterial Infections; Biological; Biopsy; Black American; Blood; Chronic; Clinical; Clinical Data; Communities; Consent; Cost Savings; Counseling; Creatinine; DNA; Data; Disadvantaged; Disparity; Disparity population; Donor Exclusions; Donor person; Economic Factors; Education; Eligibility Determination; End stage renal failure; Enrollment; Ensure; Environmental Risk Factor; European; Evaluation; Face; Failure; Focal and Segmental Glomerulosclerosis; Foundations; Genes; Genetic; Genetic Risk; Genetic Screening; Genotype; Geography; Goals; Graft Survival; HLA Antigens; Health Care Costs; Hypertension; Immunosuppression; Individual; Informed Consent; Kidney; Kidney Diseases; Kidney Failure; Kidney Transplantation; Knowledge; Lesion; Living Donors; Longterm Follow-up; Measures; Medical; Organ; Organ Procurements; Outcome; Participant; Pattern; Phase; Phenotype; Policies; Population; Prevalence; Proteinuria; Qualifying; Quality of life; Recurrent disease; Registries; Renal function; Reporting; Request for Applications; Research; Risk; Role; Safety; Serum; Site; Slide; Time; Transplant Recipients; Transplantation; United Network for Organ Sharing; United States National Institutes of Health; Universities; Urine; Variant; Virus Diseases; Work; academic program; clinical center; cohort; digital pathology; ethnic difference; experience; follow-up; genetic risk factor; graft failure; high risk; improved; kidney biopsy; living kidney donor; nephrogenesis; non-diabetic; novel; organ allocation; post-transplant; primary outcome; programs; prospective; racial difference; recruit; repository; response; risk variant; secondary outcome; social; targeted treatment; transplant centers

An excess burden of chronic kidney and end stage renal disease is experienced by Black Americans. Risk variants in the apolipoprotein-1 (APOL1) gene, found almost exclusively in individuals of African ancestry, are associated with several forms of non-diabetic kidney disease in Black Americans, including focal segmental glomerulosclerosis, HIV-associated nephropathy, and hypertension-related kidney disease. These APOL1 risk variants explain up to 70% of the excess risk in Black Americans with these kidney diseases. However, presence of these risk variants does not guarantee development of kidney disease, with secondary genetic or environmental hits required. This along with lack of targeted therapies makes the value of genetic screening for APOL1 risk variants unknown. The impact of APOL1 risk variants in kidney transplantation, for both donors and recipients, is understudied. It is unknown if living kidney donors with APOL1 risk variants are at increased risk for development of kidney disease post donation. For recipients, initial studies have suggested that recipients who receive donor kidneys with two APOL1 risk variants may have worse graft outcomes. Due to both biological and social-economic factors, Black Americans have been historically disadvantaged in receiving kidney transplants, and the theoretical practice of APOL1 genetic screening and excluding donors with risk variants could further disadvantage this population. These multiple questions highlight the need to thoroughly examine the impact of APOL1 risk alleles on transplant outcomes. The NIH- sponsored APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO) is addressing this important question by uniting transplant centers, organ procurement organizations (OPOs), and the United Network for Organ Sharing (UNOS) to enroll donors of African ancestry and their kidney recipients, then follow their transplant outcomes. In Phase 1 of APOLLO, we have functioned as an ideal clinical center in direct response to original request for application by enrolling 154 qualifying deceased donor recipients, living donors, and living donor recipients through partnerships with 8 transplant centers in addition to our primary Vanderbilt University Medical Clinical Center, providing DNA, biospecimens, and essential longitudinal clinical data. Our aligned transplant centers include large academic programs as well a small community programs to strive for the goal of universal enrollment. We have worked seamlessly with the other Clinical Centers and the SDRC, as well as partnered with OPOs and UNOS, to build a strong foundation for APOLLO. For Phase 2, we will continue the important work of the APOLLO Consortium through accomplishment of several aims. In Aim 1, we will prospectively collect long-term follow-up data on all APOLLO participants and enroll additional living donors. In Aim 2, we will provide detailed clinical data and biospecimens on APOLLO participants as well as kidney transplant biopsy slides from our Clinical Center. In Aim 3, we will facilitate return of APOL1 genotype results. Once completed, these Aims will advance our knowledge of APOL1 in kidney transplantation.

美国黑人经历了慢性肾脏和终末期肾脏疾病的过重负担。 载脂蛋白-1(APOL1)基因的风险变异几乎只在非洲血统的个人中发现， 在美国黑人中与几种形式的非糖尿病肾脏疾病有关，包括局灶性 节段性肾小球硬化、HIV相关肾病和高血压相关肾脏疾病。这些 在患有这些肾脏疾病的美国黑人中，APOL1风险变异可以解释高达70%的额外风险。 然而，这些风险变异的存在并不保证肾脏疾病的发展，继发性肾脏疾病 需要基因或环境方面的打击。这一点，加上缺乏有针对性的治疗，使得基因治疗的价值 APOL1风险变异的筛查未知。载脂蛋白1风险变异对肾移植的影响 无论是捐赠者还是接受者，都没有得到充分的研究。目前尚不清楚携带APOL1风险变异的活体肾脏捐赠者是否 献血后患肾脏疾病的风险增加。对于接受者，初步研究有 提示接受含有两个APOL1风险变异的供体肾脏的受者移植肾情况可能更差。 结果。由于生物和社会经济因素，美国黑人在历史上 肾移植受者的弱势群体及APOL1基因筛查的理论与实践 将具有风险变异的捐赠者排除在外可能会进一步使这一群体处于不利地位。这多个问题 强调需要彻底检查APOL1风险等位基因对移植结果的影响。美国国立卫生研究院- APOL1赞助的长期肾脏移植成果网络(Apollo)正在解决这一问题 联合移植中心、器官采购组织(OPO)和美国 器官共享网络(UNOS)招募非洲血统的捐赠者及其肾脏接受者，然后 他们的移植结果。在阿波罗计划的第一阶段，我们直接成为了一个理想的临床中心 通过登记154名符合资格的已故活体捐赠者来回应最初的申请请求 捐赠者和活体捐赠者接受者通过与8个移植中心的合作伙伴关系除了我们的主要 范德比尔特大学医学临床中心，提供DNA、生物样品和必要的纵向临床 数据。我们的联合移植中心包括大型学术项目以及小型社区项目 为实现全民招生目标而努力。我们与其他临床中心和 国家发改委以及与OPOS和UNOS的合作，为阿波罗奠定了坚实的基础。对于第二阶段，我们 将通过实现几个目标继续阿波罗联盟的重要工作。在目标1中， 我们将前瞻性地收集所有阿波罗参与者的长期跟踪数据，并招募更多的生活 捐赠者。在目标2中，我们将提供详细的临床数据和阿波罗参与者的生物制品以及 来自我们临床中心的肾移植活组织切片。在目标3中，我们将促进APOL1基因的回归 结果。一旦完成，这些目标将促进我们对肾移植中APOL1的了解。