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

项目摘要/摘要 慢性肾脏病(CKD) 个人 其中 恶性载脂蛋白L1(APOL1)。 大约13%的非裔美国人和25%的西非人携带高危肾脏基因型， 由两个APOL1风险变种G1和G2的任意组合组成。 再次提交以患者为中心的国家糖尿病和消化系统疾病研究所 研究职业发展奖(K23)旨在支持Titilayo Ilori博士，他是该大学的助理教授 波士顿大学医学院，他想要建立一个专注于机械和介入的职业 饮食因素和生活方式对慢性肾脏病低、中、重度发病和发展影响的研究 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。伊洛里医生的前科 研究的重点是慢性肾脏病的健康差异和营养相关暴露的次要数据分析。 以及肾脏疾病的结果。Ilori博士打算将她的研究范围扩展到设计 研究膳食钠和钾在慢性肾脏病进展和载脂蛋白1中的作用的前瞻性研究 非洲人的肾病。因此，她的K23培训侧重于获得全球卫生研究方面的技能， CKD的营养和遗传流行病学，纵向的统计遗传学和高级生物统计技术 数据分析，慢性肾脏病的生物标志物。 我们提出了一个利用非洲肾脏疾病的人类遗传与健康的研究项目 研究网络，解决以下研究目标：1)横断面和前瞻性 通过24小时尿液评估膳食钠、钾和草酸盐摄入量之间的关系 非洲人的收藏；2)一项横断面和前瞻性研究，以确定饮食与 CKD和CKD进展的模式；3)饮食：基因交互研究，以检查饮食因素 (钠、钾、草酸或饮食模式)改变APOL1肾脏基因关联对 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 在SSA的非洲人中CKD进展的因素，那里的透析和肾移植的费用是 令人望而却步。此外，饮食改变高危APOL1肾病患者的肾病风险的证据 危险等位基因在研究APOL1肾病的新治疗靶点方面可能很重要。 在撒哈拉以南非洲(SSA)，2%的人被判处死刑 患有终末期肾病(ESRD)的患者可以进行维持性透析或移植。 患有CKD的非洲人，肾功能下降更快，ESRD发病更早。这 CKD表型在很大程度上归因于编码基因的变异

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