9/14 APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO) Clinical Center

9/14 APOL1 长期肾移植结果网络 (APOLLO) 临床中心

• 批准号: 10731303
• 负责人: Sylvia E Rosas
• 金额: $ 32.4万
• 依托单位: JOSLIN DIABETES 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/10731303
• 关键词: APOL1 gene; Acceleration; Acute; Address; African American; African American population; African ancestry; Albumins; Alleles; Allografting; American; Antibodies; Apolipoproteins; Arizona; Bacterial Infections; Basic Science; Biological Specimen Banks; Biopsy; Blood; Chronic; Chronic Kidney Failure; Clinic; Clinical Data; Clinical Research; Consent; Cost Savings; Counseling; Creatinine; DNA; Data; Deterioration; Diabetes Mellitus; Diagnostic; Disparity; Donor person; Education; Eligibility Determination; End stage renal failure; Enrollment; Ensure; Environmental Risk Factor; European; Evaluation; Face; Failure; Future; General Hospitals; Genes; Genetic; Genetic Variation; Genotype; Geography; Graft Survival; HLA Antigens; Hand; Health; Health Care Costs; Hospitals; Immunosuppression; Individual; Infrastructure; Interdisciplinary Study; Israel; Kidney; Kidney Failure; Kidney Transplantation; Lesion; Living Donors; Longterm Follow-up; Massachusetts; Measures; Medical; Medical center; Organ; Outcome; Participant; Patients; Pattern; Phase; Phenotype; Policies; Prevalence; Proteinuria; Public Health; Quality of life; RNA; Recurrent disease; Registries; Renal Replacement Therapy; Renal function; Reporting; Research; Resources; Risk; Role; Safety; Science; Serum; Site; Slide; Therapeutic; Time; Translational Research; Transplant Recipients; Transplantation; United Network for Organ Sharing; United States National Institutes of Health; Universities; Urine; Variant; Virginia; Virus Diseases; Woman; clinical center; cohort; data repository; digital pathology; ethnic difference; experience; follow-up; gene interaction; genetic risk factor; graft failure; high risk; improved; kidney biopsy; living kidney donor; novel; policy implication; post-transplant; primary outcome; prognostic; programs; prospective; protocol development; racial difference; recruit; repository; risk variant; secondary outcome

PROJECT SUMMARY/ABSTRACT Successful kidney transplant reverses many of the chronic abnormalities in chronic kidney disease (CKD) and has shown to improve not only quality of life but also patient survival compared to renal replacement therapy. It is vital to identify strategies that improve and prolong organ function. APOL1 risk alleles have been shown to explain in part the increased risk of African Americans compared to non-African American for end-stage kidney disease. However, the association of APOL1 alleles with kidney transplant outcomes such as deterioration of kidney function, acute rejection, and allograft loss as well as living donor health is unclear. APOL1 genotyping has the potential to reduce the discard of good-quality kidneys from AA donors and increase the number of transplants overall. We are responding to RFA-DK-22-506 – “APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO) Clinical Centers”, to continue as a clinical center that builds upon the accomplishments of our established multidisciplinary research group in the first phase. As a successful recruitment site with our aligned 19 transplant programs, the proposal builds upon an established infrastructure and our experience recruiting APOLLO participants. In Phase 1 of APOLLO, we have successfully consented 156 kidney transplant recipients and 12 living donors, with DNA on hand in 151 recipients (97%) and 12 donors (100%), across these centers. We propose to collect long-term follow-up data on all APOLLO participants. (Aim 1); to provide detailed clinical data and biospecimens on APOLLO participants from our CC providing unique data not available in national registries: kidney biopsy results, acute rejection types and treatment, recurrent disease, changes in immunosuppression, medical compliance, bacterial and viral infections, proteinuria, creatinine and donor specific HLA antibodies, among others (Aim 2); and to facilitate return of APOL1 genotype results to participants (Aim 3). We are committed to collaborative protocol development, sharing best practices, and team science to achieve the APOLLO’s objectives. The APOLLO network has established a high-quality resource (data and specimen repository of blood, urine, DNA, and RNA) for future basic, clinical and translational research in transplantation. The proposed research plan will have future diagnostic, prognostic and therapeutic implications. In addition, it could have policy implications as kidneys may need to be allocated in the future taking into account the donor APOL1 genotype. The proposed research plan, by improving our understanding of the impact of APOL1 gene in kidney transplantation, has the potential to dramatically impact public health and diminish kidney discards for transplantation.

项目概要/摘要 成功的肾移植可逆转慢性肾病 (CKD) 和 与肾脏替代疗法相比，它不仅可以改善生活质量，还可以提高患者的生存率。 已证明 APOL1 风险等位基因对于确定改善和延长器官功能的策略至关重要。 部分解释了非裔美国人与非非裔美国人相比终末期肾病的风险增加 然而，APOL1 等位基因与肾移植结果（例如肾功能恶化）之间的关联。 肾功能、急性排斥反应、同种异体移植物丢失以及活体捐赠者的健康状况尚不清楚。 有潜力减少 AA 捐献者优质肾脏的丢弃并增加 我们正在回应 RFA-DK-22-506 –“APOL1 长期肾脏移植” 结果网络（APOLLO）临床中心”，继续作为一个建立在 我们建立的多学科研究小组第一阶段的工作取得了成功。 招募网站与我们一致的 19 个移植项目，该提案建立在已建立的基础设施之上 以及我们招募 APOLLO 参与者的经验 在 APOLLO 第一阶段，我们已成功获得同意。 156 名肾移植受者和 12 名活体捐献者，其中 151 名受者 (97%) 和 12 名捐献者现有 DNA (100%)，跨越这些中心。 我们建议收集所有 APOLLO 参与者的长期随访数据（目标 1）； 来自我们的 CC 的 APOLLO 参与者的数据和生物样本提供了国家/地区未提供的独特数据 登记处：肾活检结果、急性排斥类型和治疗、复发性疾病、变化 免疫抑制、医疗依从性、细菌和病毒感染、蛋白尿、肌酐和供体 特定 HLA 抗体等（目标 2）；并促进 APOL1 基因型结果返回 参与者（目标 3）。 团队科学来实现 APOLLO 的目标 APOLLO 网络建立了高质量的团队。 资源（血液、尿液、DNA 和 RNA 的数据和样本存储库），用于未来的基础、临床和 拟议的研究计划将具有未来的诊断、预后作用。 此外，它还可能产生政策影响，因为可能需要分配肾脏。 未来考虑到供体 APOL1 基因型，通过改进我们提出的研究计划。 了解 APOL1 基因在肾移植中的影响，有可能产生巨大影响 公共卫生和减少移植肾废弃量。