14/14 APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO) Scientific Data Research Center

14/14 APOL1长期肾移植结果网络（APOLLO）科学数据研究中心

• 批准号: 10728589
• 负责人: DONALD W BOWDEN
• 金额: $ 90.1万
• 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 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10728589
• 关键词: APOL1 gene; Acute; Adult; African American; African American population; African ancestry; Allografting; American; Ancillary Study; Apolipoproteins; Archives; Bioinformatics; Biometry; Childhood; Chronic Kidney Failure; Clinical; Clinical Data; Cohort Studies; Collection; Communities; Creatinine; DNA; Data; Data Analyses; Databases; Decision Making; Development; Disparity; Eligibility Determination; Engraftment; Enrollment; Ensure; Ethicists; Ethics; Ethnic Population; European; Evaluation; Failure; Genes; Genetic; Genotype; Glomerular Filtration Rate; Graft Survival; Health; Health Care Costs; Health protection; Histology; Human Resources; Individual; Informed Consent; Institutional Review Boards; Kidney; Kidney Transplantation; Laboratories; Leadership; Link; Manuals; Monitor; Multicenter Studies; National Institute of Diabetes and Digestive and Kidney Diseases; Nephrology; Observational Study; Operative Surgical Procedures; Organ; Organ Procurements; Outcome; Outcome Assessment; Participant; Patients; Physicians; Population; Predisposition; Procedures; Process; Prospective Studies; Proteinuria; Protocols documentation; Publications; Quality of life; Renal function; Reporting; Research; Research Personnel; Resources; Retrospective Studies; Risk; Safety; Sampling; Serum; Sickle Hemoglobin; Statistical Data Interpretation; Structure; Time; Transplant Recipients; Transplantation; United Network for Organ Sharing; United States National Institutes of Health; Universities; Variant; Virus Diseases; Vital Status; Work; biobank; clinical center; data quality; design; donor-specific antibody; ethnic disparity; forest; genetic information; genome-wide; graft function; improved; kidney allograft; living kidney donor; medical schools; organ allocation; organ procurement transplantation network; post-transplant; precision medicine; primary outcome; programs; prospective; racial population; recruit; repository; response; risk variant; skills; tool; web site; working group

The NIH APOL1 Long-term Transplantation Outcomes Network (APOLLO) Collaborative U01 is performing a national prospective evaluation of donor and recipient apolipoprotein L1 gene (APOL1) risk variants in US kidney transplants from African American donors to determine their effect on transplant outcomes. In addition, post- donation health and kidney function of African American living kidney donors will be assessed. We are applying to continue serving as the APOLLO Scientific and Data Research Center (SDRC). Shorter renal allograft survival is observed for transplantations from deceased African American kidney donors, relative to deceased European American kidney donors. Reasons for this are unknown, but retrospective reports suggest that presence of two APOL1 risk variants in kidney donors may contribute to the disparity. These variants are common in populations with recent African ancestry (such as African Americans), where they are strongly associated with chronic kidney disease, but rare in other racial/ethnic groups. APOL1 genotype data may provide more accurate assessment of the likelihood for long-term renal allograft function in donor kidneys, thereby improving matching of donor kidneys with potential recipients in order to optimize renal allograft and patient survival. This information may better inform physicians about organ quality prior to making decisions on allocation. It may also inform the safety of living kidney donation. Before APOL1 genotypes can be used clinically, the prospective national APOLLO study was required to evaluate kidney transplant outcomes from African American donors and recipients of their kidneys based on APOL1. APOLLO collects information lacking from retrospective studies, including recipient APOL1 genotypes, renal histology in engrafted kidneys and presence or development of BK viral infections, donor specific antibodies, and acute rejections after kidney transplantation. We apply to continue to perform these activities for the APOLLO Network: overall study coordination, assist with ensuring compliance with the Protocol and Manual of Procedures, maintain data tracking tools and the study website, collect and archive clinical and outcomes data, perform genotyping, statistical analyses, assessment of outcomes including the primary outcome “time to allograft failure in transplanted kidneys from African American donors based on donor APOL1 genotypes”, and complete the bio-repository. We will longitudinally assess vital status, kidney function and proteinuria in living African American kidney donors based on APOL1 genotypes and prospectively assess effects of donor APOL1 genotypes on serum creatinine concentration, estimated glomerular filtration rate, and proteinuria in kidney transplant recipients with functioning grafts. APOLLO results have the potential to transform the organ allocation and informed consent processes in kidney transplantation, optimize renal allograft survival, reduce discard of good-quality kidneys, and protect the health of living kidney donors.

NIH APOL1 长期移植结果网络 (APOLLO) 协作 U01 正在执行一项 美国肾脏供者和受者载脂蛋白 L1 基因 (APOL1) 风险变异的国家前瞻性评估 来自非裔美国捐赠者的移植以确定其对移植结果的影响。此外，后 将评估非裔美国人活体肾脏捐赠者的捐赠健康和肾功能。我们正在申请 继续担任阿波罗科学和数据研究中心（SDRC）。同种异体肾移植存活期较短 相对于已故的欧洲人，观察到已故非裔美国人肾脏捐赠者的移植 美国肾脏捐赠者。造成这种情况的原因尚不清楚，但回顾性报告表明，存在两种情况 肾脏捐赠者的 APOL1 风险变异可能会导致这种差异。这些变异在人群中很常见 具有最近的非洲血统（例如非裔美国人），他们与慢性肾病密切相关 疾病，但在其他种族/族裔群体中罕见。 APOL1 基因型数据可以提供更准确的评估 供体肾脏具有长期同种异体移植肾功能的可能性，从而改善供体的匹配 与潜在受体的肾脏，以优化同种异体肾移植和患者生存。该信息可能 在做出分配决定之前更好地告知医生器官质量。它还可以告知安全 活体肾脏捐赠。在APOL1基因型应用于临床之前，未来国家APOLLO 需要进行研究来评估非裔美国捐赠者和接受者的肾移植结果 基于 APOL1 的肾脏。 APOLLO 收集回顾性研究中缺乏的信息，包括接受者 APOL1 基因型、移植肾脏的肾脏组织学以及 BK 病毒感染的存在或发展， 供体特异性抗体和肾移植后的急性排斥反应。我们申请继续履行 APOLLO 网络的这些活动：总体研究协调，协助确保遵守 协议和程序手册，维护数据跟踪工具和研究网站，收集和存档 临床和结果数据，进行基因分型、统计分析、结果评估，包括 主要结局“非裔美国捐赠者移植肾脏的同种异体移植失败时间（基于捐赠者） APOL1基因型”，并完成生物资源库。我们将纵向评估生命状态、肾功能 根据 APOL1 基因型对活体非裔美国肾脏捐赠者的蛋白尿和蛋白尿进行前瞻性评估 供体 APOL1 基因型对血清肌酐浓度、估计肾小球滤过率和 具有功能移植物的肾移植受者的蛋白尿。 APOLLO 结果有可能改变 肾移植中的器官分配和知情同意流程，优化肾同种异体移植物的存活率， 减少优质肾脏的废弃，保护活体肾捐献者的健康。

项目成果

APOL1 genotyping in kidney transplantation: to do or not to do, that is the question? (pro).

• DOI: 10.1016/j.kint.2020.11.025
• 发表时间: 2021-07
• 期刊: Kidney international
• 影响因子: 19.6
• 作者: Freedman BI;Poggio ED
• 通讯作者: Poggio ED

Recipient APOL1 Genotype Effects on Outcomes After Kidney Transplantation.

受者 APOL1 基因型对肾移植后结果的影响。

• DOI: 10.1053/j.ajkd.2021.11.001
• 发表时间: 2022
• 期刊: American journal of kidney diseases : the official journal of the National Kidney Foundation
• 作者: Freedman,BarryI;Mena-Gutierrez,AlejandraM;Ma,Lijun
• 通讯作者: Ma,Lijun

Mechanisms of Injury in APOL1-associated Kidney Disease.

• DOI: 10.1097/tp.0000000000002509
• 发表时间: 2019-03
• 期刊: Transplantation
• 影响因子: 6.2
• 作者: Ma L;Divers J;Freedman BI
• 通讯作者: Freedman BI

Impact of education on APOL1 testing attitudes among prospective living kidney donors.

• DOI: 10.1111/ctr.14516
• 发表时间: 2022-01
• 期刊: Clinical transplantation
• 影响因子: 2.1

Integrating APOL1 Kidney-risk Variant Testing in Live Kidney Donor Evaluation: An Expert Panel Opinion.

• DOI: 10.1097/tp.0000000000003641
• 发表时间: 2021-10-01
• 期刊: Transplantation
• 影响因子: 6.2
• 作者: Doshi MD;Gordon EJ;Freedman BI;Glover C;Locke JE;Thomas CP
• 通讯作者: Thomas CP