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

• 批准号: 9977187
• 负责人: Rasheed Adebayo Gbadegesin
• 金额: $ 13.33万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 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 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9977187
• 关键词: AIDS-Associated Nephropathy; APOL1 gene; Acute; Address; African; African American; Aliquot; Allografting; American; Ancillary Study; Antibodies; Antibody titer measurement; Apolipoproteins; Biopsy; Blood; Chronic Kidney Failure; Clinical; Clinical Data; Clinical Trials; Clinical and Translational Science Awards; Complex; Cost Savings; Creatinine; DNA; Data; Development; Dialysis procedure; Disease; 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; Informed Consent; Inherited; Kidney; Kidney Diseases; Kidney Transplantation; Lead; Lesion; 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; Renal function; Reporting; Research; Resources; Retrospective Studies; Risk Factors; Safety; Serum; Site; Specimen; Survival Rate; Tissues; Transplant Recipients; Transplantation; United States National Institutes of Health; Universities; Urine; Variant; Virus Diseases; Vital Status; Work; academic program; base; clinical center; cohort; delayed graft function; design; ethnic difference; ethnic disparity; follow-up; forest; high risk; implantation; improved; kidney allograft; living kidney donor; non-diabetic; novel; organ allocation; peripheral blood; precision medicine; preimplantation; programs; prospective; rare variant; recruit; repository; risk variant

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临床中心参与这项国家前瞻性研究。国家卫生研究院 APOL1长期移植结果网络（APOLLO）协作U01将执行一项全国性的 对美国所有肾移植中供体和受体APOL 1肾脏风险变异的前瞻性评估 非裔美国人捐赠者，以确定他们对移植结果的影响。此外，生活的健康 非裔美国人的肾脏捐赠者将接受评估。既往回顾性研究缺乏的信息 需要收集，包括同种异体移植失败的肾组织学数据和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。我们的调查 由两名专业知识互补的PI领导的团队在临床试验中发挥了主导作用，以解决 在患有终末期肾病的非裔美国人中的差异。非洲死者的肾移植 美国肾脏捐献者的寿命不如来自已故欧洲裔美国人的肾脏捐献者长 捐助者。其原因尚不清楚，但回顾性报告表明，存在两种载脂蛋白， L1（APOL1）基因肾风险变异体在肾脏捐赠者可能有助于。这些肾脏风险变异在以下人群中很常见： 最近有非洲血统的人群（如非洲裔美国人），他们与 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。APOL1 基因型数据可能被证明是临床上有用的，在那些最近的非洲血统的设置分配 用于移植的已故供体肾脏和评估潜在的活体肾脏供体。基因型 信息（精确医学）可以更准确地评估长期肾功能衰竭的可能性。 在供体肾中的同种异体移植物功能，从而改善供体肾与潜在受体的匹配， 优化肾移植物和患者存活率。信息可以更好地告知医生器官质量， 分配的决定。然而，在这些基因型数据可用于临床之前， 需要进行一项前瞻性国家研究，以评估非裔美国人的肾移植结局 基于APOL1基因型的肾脏供体和受体。缺乏既往回顾性研究的信息 将收集研究，包括同种异体移植失败的肾组织学数据和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。这就是 和当前APOLLO试验的设置。在这项重要的多中心研究中，我们的研究中心将与 APOLLO科学和数据研究中心和其他参与研究中心进行招募， 根据APOLLO方案，随访合格的肾脏供体和移植受体。结果显示， 有可能改变肾移植中的器官分配和知情同意过程， 提高移植肾存活率，减少优质肾的弃用，保护活体肾的健康 捐助者。