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.

我们正在申请作为 APOLLO 临床中心参与这项全国性前瞻性研究。美国国立卫生研究院 APOL1 长期移植结果网络 (APOLLO) 合作组织 U01 将进行全国性移植手术对美国所有肾移植中供体和受体 APOL1 肾脏风险变异的前瞻性评估非裔美国捐赠者确定其对移植结果的影响。另外，生活健康非裔美国肾脏捐赠者将接受评估。先前回顾性研究中缺乏的信息需要收集，包括同种异体移植失败的肾脏组织学数据以及 BK 的存在或发展病毒感染、供体特异性抗体和肾移植后的急性排斥反应。我们的调查由两名具有互补专业知识的 PI 领导的团队在临床试验中处于领先地位，以解决显着的问题患有终末期肾病的非裔美国人之间的差异。已故非洲人的肾移植美国肾脏捐赠者的寿命不如已故欧洲裔美国肾脏捐赠者的寿命长捐助者。其原因尚不清楚，但回顾性报告表明，两种载脂蛋白的存在肾脏捐赠者的 L1 (APOL1) 基因肾脏风险变异可能有所贡献。这些肾脏风险变异常见于具有近代非洲血统的人群（例如非洲裔美国人），他们与非洲人密切相关非糖尿病终末期肾病。相比之下，这些风险变异在其他种族群体中很少见。美国POL1 基因型数据可能被证明在临床上对具有非洲血统的人在分配方面有用用于移植的已故捐献者肾脏和对未来活体肾脏捐献者的评估。基因型信息（精准医学）可以更准确地评估长期肾病的可能性供体肾脏的同种异体移植功能，从而改善供体肾脏与潜在受体的匹配优化同种异体肾移植和患者生存。信息可以更好地让医生事先了解器官质量分配决定。然而，在这些基因型数据用于临床之前，需要前瞻性全国研究来评估非裔美国人的肾移植结果基于 APOL1 基因型的肾脏捐赠者和接受者。先前回顾中缺乏信息将收集研究，包括同种异体移植失败的肾脏组织学数据以及 BK 的存在或发展病毒感染、供体特异性抗体和肾移植后的急性排斥反应。这就是道理以及当前 APOLLO 试验的设置。在这项重要的多站点研究中，我们的站点将与阿波罗科学与数据研究中心及其他参与站点招募和前瞻性根据 APOLLO 协议跟踪符合条件的肾脏捐赠者和移植受者。结果有改变肾移植器官分配和知情同意流程的潜力，优化提高同种异体肾的成活率，减少优质肾的报废，保护活体肾的健康捐助者。