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.

项目总结/摘要 成功的肾移植逆转了慢性肾病（CKD）中的许多慢性异常， 与肾脏替代疗法相比，已显示不仅改善生活质量，而且改善患者生存率。它 对于确定改善和延长器官功能的策略至关重要。APOL 1风险等位基因已被证明 部分解释了与非非洲裔美国人相比，非洲裔美国人患终末期肾病的风险增加 疾病然而，APOL 1等位基因与肾移植结果的相关性，如肾功能恶化， 肾功能、急性排斥反应、同种异体移植物丢失以及活体供者的健康状况尚不清楚。APOL 1基因分型 有可能减少AA供体的优质肾脏的丢弃，并增加 整体移植我们正在回应RFA-DK-22-506 -“APOL 1长期肾移植 结果网络（APOLLO）临床中心”，继续作为一个临床中心，建立在 我们成立的多学科研究小组在第一阶段的成就。作为一个成功 招募网站与我们的19个移植计划一致，该提案建立在一个既定的基础设施之上 以及我们招募阿波罗计划参与者的经验在APOLLO的第一阶段，我们已经成功地同意 156名肾移植受者和12名活体供者，151名受者（97%）和12名供者手头有DNA (100%），这些中心。 我们建议收集所有APOLLO参与者的长期随访数据。(Aim 1）提供详细的临床资料 来自我们CC的APOLLO参与者的数据和生物标本，提供了国家无法获得的独特数据 登记研究：肾活检结果、急性排斥类型和治疗、疾病复发、 免疫抑制、医疗依从性、细菌和病毒感染、蛋白尿、肌酐和供体 特异性HLA抗体等（目标2）;并促进APOL 1基因型结果返回， 参与者（目标3）。我们致力于合作开发协议，分享最佳实践， 团队科学来实现阿波罗的目标。APOLLO网络建立了一个高质量的 资源（血液、尿液、DNA和RNA的数据和标本库），用于未来的基础、临床和 移植中的转化研究。拟议的研究计划将有未来的诊断，预后， 和治疗意义。此外，这可能会产生政策影响，因为肾脏可能需要分配 在将来考虑供体APOL 1基因型。拟议的研究计划，通过改善我们的 了解APOL 1基因在肾移植中的影响，有可能极大地影响 公共卫生和减少肾移植丢弃。