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Kidney Transplant Outcomes and APOL1

肾移植结果和 APOL1

基本信息

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
项目类别：
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

项目摘要

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.

项目总结