The Interplay between Glucose Metabolism and Heat in Kidney Disease using a Metabolomics Approach

项目摘要 Roxana Chicas博士，RN是第一代双语拉丁裔，她的目标是成为一个独立的NIH- 资助护士科学家在该领域制定可持续的研究计划， 葡萄糖代谢和 肾病K23奖的支持将提供专门的研究时间， 基本的培训和指导，以进一步她的理解：1）关系 糖代谢 途径和热暴露以及 利用代谢组学研究农民肾脏疾病 方法;和2）社区参与干预试验的设计和管理，以降低 热应激、肾功能不全和血糖失调。热是主要原因 在美国，与天气有关的死亡人数占总死亡人数的70%，而农业工人是一个特别脆弱的职业部门。 热相关疾病（HRI）。美国农业部门有200 - 300万工人面临高温风险 与此相关的死亡率是一般劳动力人口的35倍。在过去 近十年来，许多研究表明，热暴露与急性肾脏病风险之间存在联系。 损伤（AKI）。农业工人中AKI的阴险和无法解释的上升的慢性影响，以及 不成比例的HRI负担和反复热应激诱导的脱水还没有很好的理解。的 易感性健康状况（如前驱糖尿病）在AKI风险中可能发挥的作用尚未得到证实。 考察虽然研究已经记录了与热有关的风险因素和身体对热的生理反应， 热，很少有研究考虑到葡萄糖代谢和高环境热条件 是急性肾损伤的一个危险因素，但对人体代谢途径的了解较少。 热应激反应。这个项目的目标是描述农场工人的生理表型 跨季节和暴露（室内与室外），使用非靶向，高分辨率代谢组学（HRM） 比较代谢组学特征，并检查HRI临床特征（包括核心 体温、心率、脱水、HRI症状）;炎症生物标志物（IL-10，IL-6，IL-8，IL-1 β， TNF-α、HSP 72、HSP 90）;肾生物标志物（血清肌酐、BUN、eGFR、蛋白尿、尿酸;醛固酮， 和肽素）;和葡萄糖临床特征（HbA1c、AM空腹血糖和PM血糖水平）。 这项研究将探讨糖代谢和HRI的相互作用，并促进我们对HRI的理解。 AKI和肾功能的生理基础。代谢组学特征的结合将增加 通过指出潜在的代谢机制和结果的科学状态 热应激的生理反应

PROJECT SUMMARY Roxana Chicas, PhD, RN is a 1st generation bilingual Latina and her goal is to become an independent NIH- funded nurse scientist developing a sustainable research program in the area of glucose metabolism and kidney disease. Support from the K23 award will provide the dedicated research time that will enable fundamental training and mentorship to further her understanding of: 1) the relationship of glucose metabolic pathways and heat exposure and the development of kidney disease in farmworkers using a metabolomics approach; and 2) the design and management of community-engaged intervention trials to decrease the risk of heat stress, renal dysfunction, and glucose dysregulation in vulnerable populations. Heat is the leading cause of weather-related deaths in the US, and farmworkers comprise an occupational sector particularly vulnerable to heat-related illness (HRI). Between 2-3 million workers in the US agricultural industry are at risk of heat related mortality at a rate that is 35 times greater than that of the general workforce population. In the last decade a number of investigations have shown a link between heat exposure and the risk of acute kidney injury (AKI). The chronic effects of the insidious and unexplained uptick of AKI among farmworkers, and the disproportionate burden of HRI and repetitive heat stress-induced dehydration are not well understood. The role that predisposing health conditions such as prediabetes may play in the risk of AKI has not been examined. While studies have documented heat-related risk factors and the body’s physiologic response to heat, few investigations have considered whether glucose metabolism and high environmental heat conditions are a risk factor for acute kidney injury, and less is known about the metabolic pathways underlying the body’s response to heat stress. The goal of this project is to characterize the physiologic phenotypes of farmworkers across seasons and exposures (indoors v. outdoors), using non-targeted, high-resolution metabolomics (HRM) to compare metabolomic profiles, and examine the associations between HRI clinical profiles (including core body temperature, heart rate, dehydration, HRI symptoms); inflammation biomarkers (IL-10, IL-6, IL-8, IL-1β, TNF-α, HSP72, HSP90); renal biomarkers (serum creatinine, BUN, eGFR, proteinuria, uric acid; aldosterone, and copeptin); and glucose clinical profiles (HbA1c, AM fasting blood glucose, and PM blood glucose levels). This proposed study will explore interplay of glucose metabolism and HRI and advance our understanding of the physiologic underpinnings of AKI and renal function. The incorporation of metabolomic profiles will add to the state of the science by indicating the underlying metabolic mechanisms and consequences of the physiologic response to heat stress.