3/14 ApoL1 Long-Term Kidney Transplantation Outcomes Network (Apollo) Clinical Center

项目摘要 APOL 1的遗传变异通常在西撒哈拉以南非洲血统的人中发现 与肾脏疾病相关，如局灶节段性肾小球硬化症、高血压 归因终末期肾病和HIV相关肾病。存在2 死亡供体中的APOL 1-肾风险变体（RRV）与2-4倍的风险相关 移植肾丢失的风险携带APOL 1风险等位基因的活体捐献者可能有肾脏风险 疾病美国国立卫生研究院建立了“APOL 1长期肾移植结果” （APOLLO）U 01 Consortium，2017年。APOLLO联盟包括13个临床中心 (CCs)与4个配对的核心中心一起研究APOL 1的作用。约翰霍普金斯/圣刘易斯 大学CC是CC 3。阿波罗联盟的主要目标是评估 在整个美国接受AA供体肾脏的患者中的结果，或 其他近期非洲血统的个体，并评估APOL 1基因型与 与肾移植功能相关的结果。主要结果是移植失败的时间， 受惠人士其他结果包括受者肾功能的变化率， 肾移植的急性排斥反应和蛋白尿。APOLLO Consortium还表示， AA活体供体（LD）的有意义的纵向结局，重点关注生命状态和肾功能 功能，以及蛋白尿。虽然APOLLO招收了LD，但他们的相对人数一直是 有限，强调需要进行更多的研究，以更彻底地确定 APOL 1基因型与长期LD结果的关系 并通过a）提供数据， 关于APOL 1基因型对AA患者肾移植结局的影响， 供体，B）提供关于APOL 1基因型对长期存活的影响的数据，以及 AA LD及其受体的肾功能结果，以及c）建立临床资源， 以及基因数据和生物标本，供阿波罗联盟和其他未来 研究人员通过NIDDK中央存储库。

Project Summary Genetic variants in APOL1 commonly found in people of Western Sub-Saharan Africa ancestry are associated with kidney diseases such as Focal Segmental Glomerulosclerosis, Hypertension Attributed-End Stage Kidney Disease, and HIV-Associated Nephropathy. The presence of 2 APOL1- renal risk variants (RRV) in deceased donors is associated with 2-to-4-times higher risk of renal graft loss in the recipient. Living donors with APOL1 risk alleles may be at risk for kidney disease. The NIH established the “APOL1 Long-term Kidney Transplantation Outcomes” (APOLLO) U01 Consortium in 2017. The APOLLO Consortium includes 13 clinical centers (CCs) with 4 paired core Centers to study the role of APOL1. The Johns Hopkins/Saint Louis University CC is CC3. The primary objectives of the APOLLO Consortium are to assess outcomes in patients across the entire United States who receive a kidney from an AA donor, or other individuals with recent African ancestry, and to evaluate the association of APOL1 genotype with renal allograft function-related outcomes. The primary outcome is time to graft failure in the recipients. Other outcomes include the rate of change of kidney function in recipients, rates of acute rejection of the kidney transplant, and proteinuria. The APOLLO Consortium also ascertains meaningful longitudinal outcomes in AA living donors (LDs), focusing on vital status and renal function, as well as proteinuria. While APOLLO enrolls LDs, their relative numbers have been limited, highlighting the need for additional studies designed to more thoroughly define the relationships of APOL1 genotype with long-term LD outcomes This application seeks to build on and extend the findings of the APOLLO study to inform clinical practice by a) providing data regarding the effects of APOL1 genotype on outcomes of the recipients of kidneys from AA donors, b) providing data regarding the effects of APOL1 genotype on long-term survival and renal functional outcomes of AA LDs and their recipients, and c) establishing a resource of clinical and genetic data and biological specimens for the APOLLO Consortium and other future researchers through the NIDDK Central Repository.