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

使用代谢组学方法研究肾脏疾病中葡萄糖代谢与热量之间的相互作用

• 批准号: 10708153
• 负责人: Roxana Cristina Chicas
• 金额: $ 14.83万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-21 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10708153
• 关键词: Acclimatization; Acute Renal Failure with Renal Papillary Necrosis; Age; Agriculture; Aldosterone; Area; Automobile Driving; Awareness; Big Data Methods; Bioinformatics; Biological Markers; Biological Monitoring; Blood; Blood Glucose; Body Temperature; Body mass index; California; Cessation of life; Chronic; Chronic Kidney Failure; Clinical; Communities; Community Health; Complex; Creatinine; Data; Dedications; Dehydration; Development; Diabetes Mellitus; Disease Progression; Doctor of Philosophy; Early Intervention; Environment; Fasting; Florida; Funding; Future; Generations; Glucose; Glycosylated Hemoglobin; Glycosylated hemoglobin A; Goals; Guatemala; Harvest; Health; Heart Rate; Heat Stress Disorders; Heat-Shock Proteins 90; Hispanic; Hispanic Populations; IL8 gene; Immigrant; Impairment; Industry; Inflammation; Inflammatory; Interleukin-1 beta; Interleukin-10; Interleukin-6; Intervention Trial; Investigation; Kidney; Kidney Diseases; Latina; Link; Longitudinal Studies; Mentored Patient-Oriented Research Career Development Award; Mentorship; Metabolic; Metabolic Pathway; Nephrology; Non-Insulin-Dependent Diabetes Mellitus; Not Hispanic or Latino; Nurses; Occupational; Pathway Analysis; Pathway interactions; Phenotype; Physiological; Plasma; Play; Population; Prediabetes syndrome; Prevalence; Proteinuria; Protocols documentation; Renal function; Research; Resolution; Risk; Risk Factors; Role; Sampling; Science; Scientist; Seasons; Serum; Signal Transduction; Subgroup; Symptoms; TNF gene; Temperature; Time; Training; United States National Institutes of Health; Uric Acid; Vulnerable Populations; Weather; Work; bilingualism; clinical phenotype; cohort; design; disorder risk; early detection biomarkers; farm worker; glucose metabolism; health care availability; health disparity; health equity; hot climate; kidney dysfunction; metabolic profile; metabolome; metabolomics; mortality; nephrogenesis; novel; population health; programs; recruit; renal damage; response; sex; success

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.

项目总结