Effects of hydration status on kidney and gut health
Summary
Water makes up 50-60 % of total body weight in adult in humans. Water is critical in maintaining perfusion of the tissues, solute homeostasis, and almost every biological process. Low hydration status is associated with risk of kidney disease, cardiovascular disease, colon cancer, and dementia. Though the evidence proves a strong association between hydration status and certain disease conditions, there is limited data on long-term health effects of hydration in healthy individuals and in particular on the effects of recurrent heat stress that occurs in many occupations and even during vigorous recreational exercise.
Recent years have seen an increase in popularity of high intensity and extreme endurance training. Exercise causes renal vasoconstriction and reduced renal renal blood flow. It also causes increased oxidative stress and low endothelial nitric oxide synthase (eNOS). These are possible mechanisms for injury during heat stress which potentially be modified by chronic hydration status.
AIM 1: Identify effects of long term hydration status on kidney and gut. We propose to study the effects of chronic hydration status in healthy subjects. Subjects will be screened for chronic hydration status using a survey and the hydration status will be confirmed using 24 hour urine collection. We will enroll 20 chronically underhydrated and 20 adequately hydrated subjects. Baseline data including dietary logs. We will measure markers of kidney injury including KIM-1, NGAL, IL-18, ADMA, and angiotensinogen. To assess the systemic effects of the gut microbiome we will measure the gut derived uremic toxins TMAO, indoxyl sulfate, and p-cresyl sulfate. We will perform metaproteomics and measure short chain fatty acids in the stool samples from the subjects to determine the effects on hydration status on gut microbiome. The effect of diet and factors that modify the gut microbiome will be assessed. We will perform proteomic analysis in urine samples collected from the subjects to identify potential markers of hydration status.
Aim 2: Identify effect of hydration status on stress induced kidney injury in 20 healthy subjects: We will study the effect of high intensity exercise on kidney injury. We will expose 10 underhydrated and 10 well hydrated subjects to intense exercise with heat stress. We will compare the markers of kidney injury between the groups. Proteomic analysis of urine collected at the end of exercise will identify biomarkers of response and pathways analysis of proteins that are differentially abundant will reveal differences in molecular pathways that are activated during the stress between groups. We will identify gut bacterial species that differ between groups and systemic mediators of the effects of the gut microbiome that may contribute to differences in kidney injury markers between groups.
These studies will allow us to better understand the implications of hydration status in long-term health and determine how the gut microbiome interacts with acute stress. The number of subjects in each group is small because identifying subjects at the extreme of hydration is difficult and COVID restrictions allow us only to bring one subject at a time into the stress chamber. While the number of subjects is too low to make statistically significant conclusions about many of our outcomes, they will provide meaningful data to guide future studies. The results of these studies will be used for preliminary data for grants to the NIH regarding kidney health, to the DOD regarding the effects of heat and exertion on kidney function and ways to modify them, and to the USDA.
Keywords:
- kidney injury
- hydration
- gut microbiome
- uremic toxins
- exercise stress