Wake Forest Collaborative Application for an APOLLO Clinical Center

APOLLO 临床中心的维克森林协作应用程序

基本信息

批准号：
9440538
负责人：
Rasheed Adebayo Gbadegesin
金额：
$ 28.28万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
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 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9440538
关键词：
AIDS-Associated Nephropathy APOL1 gene Acute Address African African American Aliquot Allografting American Ancillary Study Antibodies Antibody titer measurement Apolipoproteins Award Biopsy Blood Chronic Kidney Failure Clinical Clinical Data Clinical Sciences Clinical Trials Complex Cost Savings Creatinine DNA Data Development Dialysis procedure Disease Eligibility Determination End stage renal failure Enrollment Ethnic group European Evaluation Failure Focal Segmental Glomerulosclerosis Future Genes Genetic Genotype Graft Survival HLA Antigens Health Health Care Costs Histologic Histology Hypertension Illinois Immunosuppression Immunosuppressive Agents Informed Consent Inherited Kidney Kidney Diseases Kidney Transplantation Lead Lesion Living Donors Medical Modeling Monitor Nephrology North Carolina Odds Ratio Organ Outcome Outcome Study Patients Pharmaceutical Preparations Physicians Policies Population Prevalence Process Prospective Studies Proteinuria Protocols documentation Quality of life Recruitment Activity Renal function Reporting Research Resources Retrospective Studies Risk Factors Safety Serum Site Specimen Survival Rate Tissues Translational Research Transplant Recipients Transplantation United States National Institutes of Health Universities Urine Variant Virus Diseases Vital Status Work academic program base cohort delayed graft function design ethnic difference ethnic disparity follow-up forest high risk implantation improved kidney allograft non-diabetic novel organ allocation peripheral blood precision medicine programs prospective rare variant repository risk variant

项目摘要

We are applying to participate as an APOLLO Clinical Center in this national prospective study. The NIH APOL1 Long-term Transplantation Outcomes Network (APOLLO) Collaborative U01 will perform a national prospective evaluation of donor and recipient APOL1 renal-risk variants in all U.S. kidney transplantations from African American donors to determine their effects on transplant outcomes. In addition, the health of living African American kidney donors will be assessed. Information that was lacking from prior retrospective studies needs to be collected, including renal histologic data in allograft failures and presence or development of BK viral infections, donor specific antibodies, and acute rejections after kidney transplantation. Our investigative team, led by two PIs with complementary expertise, has led the way in clinical trials to address the marked disparities in African Americans with end-stage kidney disease. Renal transplantations from deceased African American kidney donors do not last as long as those from deceased European American kidney donors. Reasons for this are unknown, but retrospective reports suggest that presence of two apolipoprotein L1 (APOL1) gene renal-risk variants in kidney donors may contribute. These renal-risk variants are common in populations with recent African ancestry (such as African Americans), where they are strongly associated with non-diabetic end-stage kidney disease. In contrast, these risk variants are rare in other ethnic groups. APOL1 genotype data may prove to be clinically useful in those with recent African ancestry in the setting of allocation of deceased donor kidneys for transplantation and assessment of prospective living kidney donors. Genotypic information (precision medicine) may provide more accurate assessment of the likelihood for long-term renal allograft function in donor kidneys, thereby improving the matching of donor kidneys with potential recipients to optimize renal allograft and patient survival. Information may better inform physicians about organ quality prior to decisions on allocation. However, before these genotypic data can be used in the clinical setting, a prospective national study is required to evaluate kidney transplantation outcomes from African American donors and recipients of their kidneys based on APOL1 genotypes. Information lacking from prior retrospective studies will be collected, including renal histologic data in allograft failures and presence or development of BK viral infections, donor specific antibodies, and acute rejections after kidney transplantation. This is the rationale and setting for the current APOLLO trial. In this important multi-site study, our site will work closely with the APOLLO Scientific and Data Research Center and the other participating sites to recruit and prospectively follow eligible kidney donors and transplant recipients based on the APOLLO protocol. Results have the potential to transform the organ allocation and informed consent processes in kidney transplantation, optimize renal allograft survival, reduce the discard of good-quality kidneys, and protect the health of living kidney donors.

我们正在申请参加这项国家前瞻性研究的阿波罗临床中心。 NIH APOL1长期移植成果网络（Apollo）协作U01将执行国家从美国所有肾脏移植中的供体和接受者APOL1肾风险变体的预期评估非裔美国人的捐助者确定其对移植结果的影响。此外，生活的健康将评估非裔美国人肾脏捐助者。先前回顾性研究所缺乏的信息需要收集，包括同种异体移植失败中的肾脏组织学数据以及BK的存在或发展肾移植后病毒感染，供体特异性抗体和急性拒绝。我们的调查由两个具有互补专业知识的PI领导的团队已领导临床试验，以解决标记非裔美国人患有末期肾脏疾病的差异。死者非洲人的肾脏移植美国肾脏捐赠者的持续时间不如已故欧美肾脏的供体长期持续捐助者。原因是未知的，但是回顾性报告表明存在两个载脂蛋白肾脏供体中的L1（APOL1）基因肾风险变体可能会贡献。这些肾风险变体很常见与最近非洲血统（例如非洲裔美国人）的人口，他们与非糖尿病末期肾脏疾病。相比之下，这些风险变异在其他族裔群体中很少见。 apol1 基因型数据可能被证明在临床上在近期非洲血统的人中有用已故的供体肾脏用于移植和评估潜在的活肾供体。基因型信息（精度医学）可能会更准确地评估长期肾脏的可能性供体肾脏中的同种异体功能，从而改善了供体肾脏与潜在接受者的匹配优化肾脏同种异体移植和患者存活。信息可以更好地告知医生有关器官质量的事先关于分配的决定。但是，在这些基因型数据可以在临床环境中使用之前必须使用前瞻性国家研究来评估非裔美国人的肾脏移植结果基于APOL1基因型的肾脏和肾脏的接受者。事先回顾的信息将收集研究，包括同种异体移植失败中的肾脏组织学数据以及BK的存在或发展肾移植后病毒感染，供体特异性抗体和急性拒绝。这是理由并为当前的阿波罗试验设置。在这项重要的多站点研究中，我们的网站将与阿波罗科学与数据研究中心以及其他参与网站，以招募和前瞻性根据Apollo方案遵循合格的肾脏供体和移植受者。结果具有在肾脏移植中改变器官分配和知情同意过程的潜力，优化肾脏同种异体移植生存，减少优质肾脏的丢弃并保护活肾的健康捐助者。