13/14 APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO) Clinical Center

13/14 APOL1长期肾移植结果网络（APOLLO）临床中心

• 批准号: 10728380
• 负责人: Rasheed Adebayo Gbadegesin
• 金额: $ 18.01万
• 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/10728380
• 关键词: 2019-nCoV; APOL1 gene; Acceleration; Acute; Address; African American; African American population; African ancestry; Albumins; Allografting; American; Antibodies; Apolipoproteins; Bacterial Infections; Biopsy; Blood; Clinical; Clinical Data; Consent; Cost Savings; Counseling; Creatinine; Cytomegalovirus; DNA; Data; Disparity; Donor person; Education; Eligibility Determination; End stage renal failure; Enrollment; Ensure; Environmental Risk Factor; European; Evaluation; Face; Failure; Funding; Genes; Genetic; Genotype; Geography; Graft Survival; HLA Antigens; Health; Health Care Costs; Health protection; Heart Atrium; Histology; Immunosuppression; Individual; Informed Consent; Ischemia; Kidney; Kidney Diseases; Kidney Failure; Kidney Transplantation; Lesion; Living Donors; Longterm Follow-up; Measures; Medical; Organ; Outcome; Participant; Patients; Pattern; Pharmaceutical Preparations; Phase; Phenotype; Physicians; Policies; Population; Population Group; Prevalence; Process; Proteinuria; Protocols documentation; Quality of life; Recurrent disease; Registries; Renal function; Reporting; Research; Risk; Role; Safety; Serum; Site; Slide; Time; Transplant Recipients; Transplantation; United Network for Organ Sharing; United States National Institutes of Health; Urine; Variant; Virus Diseases; Work; clinical center; cohort; digital pathology; donor-specific antibody; ethnic difference; follow-up; forest; genetic risk factor; graft failure; graft function; high risk; improved; kidney allograft; kidney biopsy; living kidney donor; novel; organ allocation; post-transplant; primary outcome; programs; prospective; racial difference; recruit; repository; risk variant; secondary outcome

We are applying to continue participating as an APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO) Study Clinical Center (CC). The NIH-funded APOLLO Study is performing a national prospective evaluation of deceased donor and recipient APOL1 risk variants in transplants from African American kidney donors to determine effects on outcomes. In addition, APOLLO studies APOL1 genotypes in African American living kidney donors for effects on their post-donation health. Kidney transplants from deceased African American donors typically do not function as long as those from European American deceased donors. Reasons for this are unknown, but retrospective reports suggest that presence of two apolipoprotein L1 (APOL1) gene risk variants in donors may contribute. The APOL1 risk variants are common in populations with recent African ancestry (such as African Americans), where they are strongly associated with end-stage kidney disease. In contrast, they are rare in other population 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 live kidney donors. Genotypic information may provide a more accurate assessment of the likelihood for long-term graft function in donor kidneys, thereby improving matching of donor kidneys with recipients to optimize graft and patient survival. Information may better inform physicians about organ quality prior to decisions on allocation. Information lacking from prior studies will be analyzed, including recipient APOL1 genotypes, kidney histology, viral infection (BK, CMV, SARS-CoV-2), donor specific antibodies, medications, cold ischemia time and acute rejection. Our investigative team, led by two PIs with complementary expertise, recruited the second largest number of eligible kidney transplant recipients in APOLLO to date. Before APOL1 genotyping can be clinically useful, a prospective national study was required to evaluate transplant outcomes from African American kidney donors and recipients of their kidneys based on their genotypes. This was the rationale and setting for the landmark APOLLO Study. Our CC has worked closely with the Wake Forest APOLLO Scientific and Data Research Center (SDRC) and the other participating CCs to recruit and prospectively follow eligible kidney donors and transplant recipients based on the APOLLO Protocol. In Phase 2, we will continue follow-up and measure urine albumin, as well as collect additional biosamples. 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.

我们正在申请继续作为APOL 1长期肾移植结局网络参与 （APOLLO）研究临床中心（CC）。NIH资助的APOLLO研究正在进行一项全国性的前瞻性研究， 非裔美国人肾移植中死亡供体和受体APOL 1风险变异的评估 捐助者确定对结果的影响。此外，APOLLO研究了非裔美国人的APOL 1基因型， 活体肾脏捐赠者对捐赠后健康的影响。已故非裔美国人的肾脏移植 供体通常不像那些来自欧洲裔美国人的已故供体那样长时间地发挥作用。其原因 是未知的，但回顾性报告表明，存在两个载脂蛋白L1（APOL 1）基因的风险， 捐助者的不同可能会有所贡献。APOL 1风险变异在最近非洲 祖先（如非洲裔美国人），他们与终末期肾病密切相关。在 相比之下，他们在其他人群中很少见。APOL 1基因型数据可能在临床上有用， 在分配已故供体肾脏进行移植的情况下， 评估潜在的活体肾脏捐赠者。基因型信息可以提供更准确的评估 供肾长期移植功能的可能性，从而改善供肾与 以优化移植物和患者的存活率。信息可以更好地告知医生器官质量 在决定分配之前。将分析既往研究缺乏的信息，包括接受者APOL 1 基因型，肾组织学，病毒感染（BK，CMV，SARS-CoV-2），供体特异性抗体，药物， 冷缺血时间和急性排斥反应。我们的调查小组，由两名专业知识互补的私家侦探领导， 招募了APOLLO迄今为止第二大数量的合格肾移植受者。APOL 1前 基因分型在临床上是有用的，需要一项前瞻性的国家研究来评估移植结果 从非裔美国人的肾脏捐赠者和他们的肾脏接受者根据他们的基因型。这是 具有里程碑意义的APOLLO研究的基本原理和背景。我们的指挥中心与维克森林阿波罗号密切合作 科学和数据研究中心（SDRC）和其他参与的CC招募并前瞻性随访 根据APOLLO协议，合格的肾脏供体和移植受体。在第二阶段，我们将继续 随访并测量尿白蛋白，以及收集额外的生物样本。APOLLO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，减少优质肾的丢弃，保护活体供肾者的健康。

项目成果

Biologic Underpinnings of Type 1 Diabetic Kidney Disease.

1 型糖尿病肾病的生物学基础。

• DOI: 10.1681/asn.2019080803
• 发表时间: 2019
• 期刊: Journal of the American Society of Nephrology : JASN
• 作者: Sedor,JohnR;Freedman,BarryI
• 通讯作者: Freedman,BarryI

Creation of a Single Institutional Review Board for Collaborative Research in Nephrology: The APOLLO Experience.

创建肾脏病学合作研究单一机构审查委员会：APOLLO 经验。

• DOI: 10.2215/cjn.0000000000000197
• 发表时间: 2023
• 期刊: Clinical journal of the American Society of Nephrology : CJASN
• 作者: Moore,JBrian;Smith,SCarrie;Russell,LaurieP;Serdoz,EmilyS;Dilts,NatalieA;Alexander,AmirA;Reboussin,DavidM;Bagwell,BenjaminM;Spainhour,MitzieH;Reeves-Daniel,AmberM;Wesley-Farrington,DeborahJ;Ma,Lijun;Freedman,BarryI;APO
• 通讯作者: APO