The Role of Dietary Nutrients in Chronic Kidney Disease Progression and Apolipoprotein L1 Nephropathy

膳食营养素在慢性肾脏病进展和载脂蛋白 L1 肾病中的作用

• 批准号: 10380175
• 负责人: Titilayo Omolara Ilori
• 金额: $ 18.52万
• 依托单位: BOSTON MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-15 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10380175
• 关键词: Address; Africa; Africa South of the Sahara; African; African American population; American; Anti-Inflammatory Agents; Apolipoproteins; Biological Markers; Biometry; Black Populations; Boston; Career Choice; Cessation of life; Chronic Kidney Failure; Collection; Cross-Sectional Studies; Data Analyses; Development; Diabetes Mellitus; Dialysis procedure; Diet; Dietary Factors; Dietary Fiber; Dietary Potassium; Dietary Practices; Dietary Sodium; Dietary intake; Disease; Disease Progression; Elements; End stage renal failure; Environmental Exposure; Environmental Risk Factor; Europe; Excretory function; Funding; Gene Expression; Genes; Genetic; Genetic Risk; Genomics; Genotype; Health; High Prevalence; Human; Incidence; Individual; Inflammasome; Inflammation; Inflammatory; Inherited; Injury to Kidney; Institutes; Intake; Intervention Studies; K-Series Research Career Programs; Kidney; Kidney Diseases; Kidney Transplantation; Life; Life Style; Link; Maintenance; Malignant - descriptor; Measures; Minority Groups; Modification; National Institute of Diabetes and Digestive and Kidney Diseases; Nutrient; Outcome; Oxalates; Parents; Participant; Patients; Phenotype; Population; Potassium; Potassium Oxalate; Prospective Studies; Prospective cohort study; Public Health; Renal function; Research; Research Project Grants; Resources; Risk; Risk Factors; Role; Sodium; Testing; Toxic effect; Training; Transplantation; Universities; Urine; Variant; biobank; blood pressure elevation; career; cost; design; dietary; disease phenotype; disorder risk; early onset; fruits and vegetables; gene environment interaction; gene interaction; genetic epidemiology; genetic risk factor; global health; health disparity; high risk; medical schools; mitochondrial dysfunction; modifiable risk; nephrotoxicity; new therapeutic target; novel; nutrition; nutritional epidemiology; patient oriented research; professor; prospective; public health research; risk variant; skills; urinary

PROJECT SUMMARY/ABSTRACT Chronic kidney disease (CKD) individuals Among malignant Apolipoprotein L1 (APOL1). Approximately 13% of African Americans and 25% of West Africans carry high risk renal genotypes, comprising of any combination of the two APOL1 risk variants, G1 and G2. This re-submission for a National Institute of Diabetes and Digestive Kidney Diseases Patient-Oriented Research Career Development Award (K23) seeks to support Dr. Titilayo Ilori, an Assistant Professor at the Boston University School of Medicine, who wants to build a career focused on mechanistic and interventional studies on the effect of dietary factors and lifestyle on CKD incidence and progression in both low- and adequately-resourced settings, especially in the context of genetic and genomic risk variants. Dr. Ilori's prior research has focused on health disparities in CKD and secondary data analysis of nutrition-related exposures and outcomes in kidney disease. Dr. Ilori intends to extend the scope of her research towards designing prospective studies to study the role of dietary sodium and potassium in CKD progression and APOL1 Nephropathy in Africans. Accordingly, her K23 training is focused on acquiring skills in global health research, nutritional and genetic epidemiology in CKD, statistical genetics and advanced biostatistics skills in longitudinal data analysis, and biomarkers of CKD. We propose a research project that leverages the Human Hereditary and Health in Africa Kidney Disease Research Network and addresses the following research aims: 1) a cross-sectional and prospective examination of the associations of dietary sodium, potassium, and oxalate intake – assessed through 24h urine collections in Africans; 2) a cross-sectional and prospective study to determine the associations of dietary patterns with CKD and CKD progression; 3) diet:gene interaction studies to examine whether dietary factors (sodium, potassium, oxalate, or dietary patterns) modify the effect of association of APOL1 renal genotypes on CKD progression. This is an important project because it may identify if dietary factors are modifiable risk factors for CKD progressions in Africans in SSA, where the cost of dialysis and renal transplantation is prohibitive. Additionally, evidence that diet alters the risk of nephropathy in those with high-risk APOL1 renal risk alleles could be important in investigating new therapeutic targets for APOL1 Nephropathy. is effectively a “death sentence” in Sub-Saharan Africa (SSA) where <2% of with end stage renal disease (ESRD) have access to maintenance dialysis or transplantation. Africans with CKD, there is a faster decline in kidney function and earlier onset of ESRD. This CKD phenotype is largely attributable to variants in the gene encoding

项目总结/摘要 慢性肾脏病（CKD） 个人 之间 恶性载脂蛋白L1（APOL 1）。 大约13%的非洲裔美国人和25%的西非人携带高风险肾基因型， 包括两种APOL 1风险变体G1和G2的任何组合。 这份重新提交给国家糖尿病和消化性肾病研究所的以患者为导向的 研究职业发展奖（K23）旨在支持博士Titilayo Ilori，助理教授在 波士顿大学医学院，谁想要建立一个职业生涯的重点是机械和介入 研究饮食因素和生活方式对慢性肾脏病发病率和进展的影响， 资源充足的环境，特别是在遗传和基因组风险变异的背景下。Ilori医生的副院长 研究集中在CKD的健康差异和营养相关暴露的二级数据分析上 和肾脏疾病的结果。Ilori博士打算将她的研究范围扩大到设计 研究饮食钠和钾在CKD进展和APOL 1中作用的前瞻性研究 非洲人的肾病因此，她的K23培训侧重于获得全球健康研究的技能， 慢性肾脏病的营养和遗传流行病学，统计遗传学和先进的生物统计学技能， 数据分析和CKD的生物标志物。 我们提出了一个研究项目，利用非洲肾脏疾病的人类遗传和健康 研究网络，并解决了以下研究目标：1）一个横截面和前瞻性 通过24小时尿液评估膳食钠、钾和草酸盐摄入量的相关性 收集在非洲人; 2）一个横断面和前瞻性研究，以确定协会的饮食 CKD和CKD进展的模式; 3）饮食：基因相互作用研究，以检查饮食因素是否 （钠、钾、草酸盐或饮食模式）改变APOL 1肾基因型对 CKD进展。这是一个重要的项目，因为它可以确定饮食因素是否是可改变的风险 SSA非洲人CKD进展的因素，其中透析和肾移植的费用是 禁止的。此外，有证据表明饮食改变了高危APOL 1肾功能不全患者的肾病风险。 风险等位基因在研究APOL 1肾病的新治疗靶点中可能是重要的。 在撒哈拉以南非洲（SSA），这实际上是一种“死刑”，其中<2%的人 终末期肾病（ESRD）患者可以接受维持性透析或移植。 非洲CKD患者肾功能下降更快，ESRD发病更早。这 CKD表型在很大程度上可归因于编码