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

长期肾移植结果网络 (APOLLO) 临床中心

基本信息

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
项目类别：
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

项目摘要

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.

美国黑人承受着慢性肾脏和终末期肾脏疾病的过度负担。载脂蛋白-1 (APOL1) 基因中的风险变异几乎只在非洲血统的个体中发现，与美国黑人中多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症、HIV 相关肾病和高血压相关肾病。这些 APOL1 风险变异解释了美国黑人患这些肾脏疾病的超额风险高达 70%。然而，这些风险变异的存在并不能保证发展为继发性肾脏疾病。需要基因或环境打击。再加上缺乏靶向治疗，基因疗法的价值就凸显出来了。筛查 APOL1 风险变异未知。 APOL1 风险变异对肾移植的影响捐助者和接受者都没有得到充分研究。目前尚不清楚携带 APOL1 风险变异的活体肾捐献者是否捐赠后患肾脏疾病的风险增加。对于接受者来说，初步研究表明表明接受具有两个 APOL1 风险变异的供体肾脏的受者可能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肾移植弱势群体APOL1基因筛查与理论实践排除有风险变异的捐赠者可能会进一步使这一人群处于不利地位。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- 赞助的 APOL1 长期肾移植结果网络 (APOLLO) 正在解决这个问题联合移植中心、器官获取组织 (OPO) 和联合国来解决这一重要问题器官共享网络（UNOS）招募非洲血统的捐赠者及其肾脏接受者，然后遵循他们的移植结果。在 APOLLO 的一期中，我们已成为直接直接治疗的理想临床中心。响应最初的申请请求，登记了 154 名合格的已故捐赠者、在世捐赠者除了我们的主要移植中心外，还通过与 8 个移植中心的合作，向捐赠者和活体捐赠者接受者提供帮助范德比尔特大学医学临床中心，提供 DNA、生物样本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和小型社区项目，以努力实现全民招生的目标。我们与其他临床中心和 SDRC 以及 OPO 和 UNOS 合作，为 APOLLO 奠定了坚实的基础。对于第二阶段，我们将通过实现多个目标来继续 APOLLO 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并登记额外的生活捐助者。在目标 2 中，我们将提供 APOLLO 参与者以及来自我们临床中心的肾移植活检切片。在目标 3 中，我们将促进 APOL1 基因型的回归结果。一旦完成，这些目标将增进我们对肾移植中 APOL1 的了解。