Kidney Transplant Outcomes and APOL1

肾移植结果和 APOL1

• 批准号: 9441559
• 负责人: Sylvia E Rosas
• 金额: $ 28.68万
• 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 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9441559
• 关键词: APOL1 gene; Acute; Adult; Affect; African; African American; Albuminuria; Alleles; Allografting; Basic Science; Blood; Caucasians; Childhood; Chronic; Chronic Kidney Failure; Clinical; Clinical Research; Comorbidity; Creatinine; Cytomegalovirus; DNA; Data; Databases; Deterioration; Diagnostic; Dialysis procedure; Disease; Disease Progression; End stage renal failure; Environmental Exposure; Functional disorder; Future; GSTM1 gene; Genes; Genetic Risk; Genetic Variation; Genetic study; Genotype; Glomerular Filtration Rate; Goals; Graft Survival; Growth; Health; Hepatitis B; Hepatitis C; Heritability; Human Herpesvirus 4; Hypertension; Immune system; Immunization; Incidence; Individual; Kidney; Kidney Diseases; Kidney Failure; Kidney Transplantation; Lead; Living Donors; Microalbuminuria; Organ; Organ Procurements; Organ Transplantation; Other Genetics; Outcome; Patients; Population; Quality of life; RNA; Recruitment Activity; Renal Replacement Therapy; Renal function; Research; Resources; Risk; Risk Factors; Role; Science; Severities; Sickle Cell Trait; Site; Specimen; Subgroup; System; Therapeutic; Time; Translational Research; Transplant Recipients; Transplantation; United Network for Organ Sharing; United States; Urine; Virus Diseases; Waiting Lists; caucasian American; clinically relevant; cost; follow-up; gene environment interaction; gene interaction; genetic risk factor; graft failure; high risk; improved; insight; mortality; multidisciplinary; policy implication; prognostic; prospective; protocol development; rate of change; repository; response; risk variant; trait

PROJECT SUMMARY Chronic kidney disease (CKD) affects >10% of the adult US population, costs tens of billions of dollars annually, and can lead to progressive kidney failure leading to need for renal replacement therapy. Successful kidney transplant reverses many of the chronic abnormalities in 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. We have established a multidisciplinary investigative team and outline plans for a multicenter transplant prospective recruiting clinical center for the RFA-DK-16-025 – “APOL1 Long- term Kidney Transplantation Outcomes Network (APOLLO) Clinical Centers”, to assess the outcome of kidney transplant recipients and living donors in relation to the African-ancestry APOL1 alleles. APOL1 risk alleles have been shown to explain a large part of the increased risk of African Americans compared to non-African American for end-stage renal 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. We propose to assess if the presence of APOL1 donor risk alleles is associated with kidney transplant outcomes (rate of change of kidney function, rates of acute rejection and graft failure defined as re- transplantation, initiation of dialysis or GFR < 15 ml/min/1.73m2) (Aim 1); to determine if acute rejection, viral infections and other genetic factors in the donor-recipient pair alters the impact of donor APOL1 risk alleles with kidney transplant outcomes (Aim 2); and determine the impact of kidney donation in African American donors with APOL1 risk alleles with up to 3.5 years of longitudinal follow-up (Aim 3). We are committed to collaborative protocol development, sharing best practices, and team science to achieve the APOLLO's objectives. The APOLLO network will also establish 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.

项目概要 慢性肾病 (CKD) 影响超过 10% 的美国成年人口，造成数百亿美元的损失 每年一次，并可能导致进行性肾衰竭，从而需要肾脏替代治疗。 肾脏逆移植可以改善 CKD 中的许多慢性异常，并且已被证明不仅可以改善质量 与肾脏替代疗法相比，不仅影响生命，而且影响患者的生存率，因此确定策略至关重要。 我们建立了一个多学科的研究小组和大纲。 计划为 RFA-DK-16-025 建立一个多中心移植前瞻性招募临床中心 – “APOL1 Long- 术语“肾移植结果网络（APOLLO）临床中心”，以评估肾移植的结果 与非洲血统 APOL1 风险等位基因相关的移植受者和活体捐赠者。 已被证明可以解释非洲裔美国人与非非洲裔美国人相比风险增加的很大一部分原因 然而，APOL1 等位基因与肾移植的关联。 肾功能恶化、急性排斥反应、同种异体移植物以及活体捐献者丧失等结果 我们建议评估 APOL1 供体风险等位基因的存在是否与肾脏相关。 移植结果（肾功能变化率、急性排斥反应率和移植失败率定义为重新移植） 移植、开始透析或 GFR < 15 ml/min/1.73m2）（目标 1）； 供体-受体中的感染和其他遗传因素改变了供体对 APOL1 风险等位基因的影响 肾移植结果（目标 2）；并确定肾脏捐赠对非裔美国捐赠者的影响 与 APOL1 风险等位基因进行长达 3.5 年的纵向随访（目标 3）。 协议开发、共享最佳实践和团队科学，以实现 APOLLO 的目标。 APOLLO网络还将建立高质量的资源（血液、尿液、 DNA 和 RNA）用于未来移植的基础、临床和转化研究。 该计划将对未来的诊断、预后和治疗产生影响，此外，它还可能具有政策意义。 考虑到供体 APOL1 基因型，未来可能需要分配肾脏。