Renal Considerations in the Heat Stress Recommendations

Study Overview
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Brief Summary
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An epidemic of chronic kidney disease is occurring in laborers who undertake physical work outdoors in hot conditions. The reason for this is unknown, but may be related to kidney dysfunction caused by increases in body temperature and dehydration. The current heat stress recommendations for workers were not developed with regards for kidney health. The purpose of this study is to determine if the current recommendations protect against kidney dysfunction.

Official Title
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Renal Considerations in the Heat Stress Recommendations

Conditions
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Hot Weather; Adverse Effect, Kidney Dysfunction, Kidney Injury, Hyperthermia, Dehydration

Intervention / Treatment
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* Other: 23.0°C WBGT - Fixed Work Rate
* Other: 25.5°C WBGT - Fixed Work Rate
* Other: 27.5°C WBGT - Fixed Work Rate
* Other: 28.5°C WBGT - Fixed Work Rate
* Other: 35.5°C WBGT - Fixed Work Rate
* Other: 26.0°C WBGT - Fixed work-to-rest ratio
* Other: 30.5°C WBGT - Fixed work-to-rest ratio
* Other: 30.5°C WBGT - Fixed work-to-rest ratio (high intensity)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women 18-44 y old Body mass index ≤35.0 kg/m2 Self-reported to be healthy. Exclusion Criteria: Not within defined age range Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2 Deemed highly active according to the physical activity questionnaire (i.e., >3500 MET*min/wk) Body mass index >35.0 kg/m2 Current or history of any renal disease, heart disease, stroke, immune or autoimmune disease, and/or gastrointestinal disease/surgery Hypertension during screening (systolic blood pressure >139 or diastolic blood pressure >89) Using medications that blunt the physiological response to exercise (e.g., beta blockers) Prescription medication with a known side effect of impaired temperature regulation or fluid balance (e.g., diuretics) Positive pregnancy test at any time during the study or breast feeding Current tobacco or electronic cigarette use or consistent use within the last 2 years Inability to safely complete the peak oxygen uptake test

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 44 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This study will systematically examine the NIOSH recommendations for prescribing work-to-rest ratios during occupational heat stress on kidney function.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fixed Work Rate<br>Participants will walk on a treadmill at 3 mph and the grade will be adjusted to elicit 430 W of metabolic heat production (the most common work intensity). This study will systematically examine the NIOSH recommendations for prescribing work-to-rest ratios with increasing environmental heat stress (defined as Wet Bulb Globe Temperature, WBGT) at this fixed rate of metabolic heat production on kidney function. | Other: 23.0°C WBGT - Fixed Work Rate<br>* For four hours, participants will walk on a treadmill to elicit 430 W of metabolic heat production in the following conditions: 23.0°C WBGT (29°C, 46% relative humidity) @ 60 min exercise per hour<br>Other: 25.5°C WBGT - Fixed Work Rate<br>* For four hours, participants will walk on a treadmill to elicit 430 W of metabolic heat production in the following conditions: 25.5°C WBGT (31°C, 52% relative humidity) @ 45 min exercise per hour<br>Other: 27.5°C WBGT - Fixed Work Rate<br>* For four hours, participants will walk on a treadmill to elicit 430 W of metabolic heat production in the following conditions: 27.5°C WBGT (33°C, 53% relative humidity) @ 30 min exercise per hour<br>Other: 28.5°C WBGT - Fixed Work Rate<br>* For four hours, participants will walk on a treadmill to elicit 430 W of metabolic heat production in the following conditions: 28.5°C WBGT (34°C, 54% relative humidity) @ 15 min exercise per hour<br>Other: 35.5°C WBGT - Fixed Work Rate<br>* For four hours, participants will walk on a treadmill to elicit 430 W of metabolic heat production in the following conditions: 35.5°C WBGT (40°C, 65% relative humidity) @ 15 min exercise per hour<br>|
| Experimental: Fixed work-to-rest ratio<br>This study will systematically examine the NIOSH recommendations on changes in kidney function when the work-to-rest ratio is fixed at 30 min per hour (the most commonly prescribed work-to-rest ratio), but the rate of metabolic heat production and environmental heat stress differs (Figure 2). As described in Study 1, the appropriate rate of metabolic heat production will be elicited by having participants walk on a treadmill at 3 mph and the grade will be adjusted accordingly. | Other: 26.0°C WBGT - Fixed work-to-rest ratio<br>* For four hours, participants will walk on a treadmill at differing levels of metabolic heat production and environmental conditions (noted below), but at a fixed work-rest ratio of 30 minutes per hour. 26.0°C WBGT (31°C, 55% relative humidity) @ 530 W metabolic heat production<br>Other: 30.5°C WBGT - Fixed work-to-rest ratio<br>* For four hours, participants will walk on a treadmill at differing levels of metabolic heat production and environmental conditions (noted below), but at a fixed work-rest ratio of 30 minutes per hour. 30.5°C WBGT (36°C, 55% relative humidity) @ 230 W metabolic heat production<br>Other: 30.5°C WBGT - Fixed work-to-rest ratio (high intensity)<br>* For four hours, participants will walk on a treadmill at differing levels of metabolic heat production and environmental conditions (noted below), but at a fixed work-rest ratio of 30 minutes per hour. 30.5°C WBGT (36°C, 55% relative humidity) @ 530 W metabolic heat production<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak urinary [IGFBP7•TIMP-2] | Kidney injury marker | through study completion, up to 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary NGAL | Kidney injury marker | through study completion, up to 20 weeks | 
| Urinary IGFBP7 | Kidney injury marker | through study completion, up to 20 weeks | 
| Urinary TIMP-2 | Kidney injury marker | through study completion, up to 20 weeks | 
| Urinary IL-18 | Kidney injury marker | through study completion, up to 20 weeks | 
| Urinary L-FABP | Kidney injury marker | through study completion, up to 20 weeks | 
| Renal artery blood velocity | Index of kidney blood flow | through study completion, up to 20 weeks | 
| Segmental artery blood velocity | Index of kidney blood flow | through study completion, up to 20 weeks |