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度负担。 载脂蛋白-1（APOL 1）基因的风险变体，几乎只在非洲血统的个体中发现， 与美国黑人的几种形式的非糖尿病肾病有关，包括局灶性肾病。 节段性肾小球硬化、HIV相关肾病和高血压相关肾病。这些 APOL 1风险变异解释了美国黑人患这些肾脏疾病的70%的超额风险。 然而，这些风险变体的存在并不能保证发生肾脏疾病， 基因或环境的影响这沿着缺乏靶向治疗，使得基因治疗的价值 筛查未知的APOL 1风险变体。APOL 1风险变异对肾移植的影响， 捐助者和受援者都没有得到充分的研究。目前尚不清楚携带APOL 1风险变异的活体肾脏供体是否 捐献后患肾病的风险增加。对于接受者，初步研究 提示接受有两种APOL 1风险变异的供体肾的受者可能会有更差的移植物 结果。由于生物和社会经济因素，美国黑人在历史上一直是 在接受肾移植中处于不利地位，以及APOL 1基因筛查的理论实践， 排除具有风险变异的献血者可能会使这一人群进一步处于不利地位。这些问题 强调需要彻底检查APOL 1风险等位基因对移植结果的影响。美国国立卫生研究院- APOL 1长期肾移植结果网络（APOLLO）正在解决这一问题 联合移植中心，器官采购组织（OPO）和联合国 器官共享网络（UNOS）招募非洲血统的捐赠者及其肾脏接受者，然后按照 移植结果。在APOLLO的第一阶段，我们作为一个理想的临床中心， 为回应原先的申请要求，登记了154名合资格的已故器官捐赠受赠人， 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，生物标本，和基本的纵向临床 数据我们的移植中心包括大型学术项目以及小型社区项目， 努力实现全民入学的目标。我们与其他临床中心和 SDRC以及与OPO和UNOS合作，为APOLLO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APOLLO参与者的长期随访数据， 捐助者。在目标2中，我们将提供APOLLO参与者的详细临床数据和生物标本，以及 我们临床中心的肾移植活检切片在目标3中，我们将促进APOL 1基因型的回归 结果一旦完成，这些目标将推进我们对APOL 1在肾移植中的认识。