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.

项目摘要 慢性肾脏疾病（CKD）影响超过10%的美国成年人口，花费数百亿美元 并且可导致进行性肾衰竭，从而需要肾替代疗法。成功 肾移植逆转了CKD的许多慢性异常， 与肾脏替代治疗相比，至关重要的是确定战略， 改善和延长器官功能。我们已经建立了一个多学科的调查小组， RFA-DK-16-025 -“APOL 1长- 术语肾移植结局网络（APOLLO）临床中心”，以评估肾移植的结局。 移植受体和活体捐赠者与非洲血统APOL 1等位基因的关系。APOL 1危险等位基因 已经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。 美国人称之为终末期肾病然而，APOL 1等位基因与肾移植的关联 结果如肾功能恶化、急性排斥反应和同种异体移植物丢失以及活体供者 健康状况不明。我们建议评估APOL 1供体风险等位基因的存在是否与肾脏疾病相关。 移植结果（肾功能变化率、急性排斥反应率和移植物衰竭定义为再 移植、开始透析或GFR < 15 ml/min/1.73m2）（目的1）;以确定是否存在急性排斥、病毒性排斥、 供体-受体对中的感染和其他遗传因素改变了供体APOL 1风险等位基因的影响， 肾移植结果（目标2）;并确定非裔美国人供体肾脏捐赠的影响 具有APOL 1风险等位基因，纵向随访长达3.5年（目标3）。我们致力于合作 协议开发，分享最佳实践和团队科学，以实现APOLLO的目标。的 APOLLO网络还将建立高质量资源（血液、尿液、 DNA和RNA）用于移植的未来基础、临床和转化研究。拟议研究 该计划将对未来的诊断、预后和治疗产生影响。此外，它还可以制定政策， 这意味着将来可能需要考虑供体APOL 1基因型来分配肾脏。