Renal Considerations in the Heat Stress Recommendations (Aim1)

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.

Study Overview

• Status: Completed
• Conditions: Hyperthermia; Kidney Injury; Dehydration; Kidney Dysfunction; Hot Weather; Adverse Effect
• Intervention / Treatment: 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)

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Bloomington, Indiana, United States, 47405-7109
      • School of Public Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 44 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fixed Work Rate; 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; 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; Other: 25.5°C WBGT - Fixed Work Rate; 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; Other: 27.5°C WBGT - Fixed Work Rate; 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; Other: 28.5°C WBGT - Fixed Work Rate; 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; Other: 35.5°C WBGT - Fixed Work Rate; 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
Experimental: Fixed work-to-rest ratio; 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; 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; Other: 30.5°C WBGT - Fixed work-to-rest ratio; 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; Other: 30.5°C WBGT - Fixed work-to-rest ratio (high intensity); 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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Core body temperature	Heat strain variable	through study completion, up to 20 weeks
Mean skin temperature	Heat strain variable	through study completion, up to 20 weeks
Oxygen uptake	Heat strain variable	through study completion, up to 20 weeks
Heart rate	Heat strain variable	through study completion, up to 20 weeks
Blood pressure	Heat strain variable	through study completion, up to 20 weeks
Whole-body sweat rate	Hydration and heat strain variable	through study completion, up to 20 weeks
Percentage change in body weight	Hydration status variable	through study completion, up to 20 weeks
Plasma osmolality	Hydration status variable	through study completion, up to 20 weeks
Urine osmolality	Hydration status variable	through study completion, up to 20 weeks
Blood and plasma volume	Hydration status variable	through study completion, up to 20 weeks
Urine specific gravity	Hydration status variable	through study completion, up to 20 weeks
Plasma copeptin	Hydration status variable	through study completion, up to 20 weeks
Creatinine clearance	Kidney function variable	through study completion, up to 20 weeks
Fractional excretion of electrolytes	Kidney function variable	through study completion, up to 20 weeks
Free water clearance	Kidney function variable	through study completion, up to 20 weeks
Serum uric acid	Kidney function variable	through study completion, up to 20 weeks
Urinary uric acid	Kidney function variable	through study completion, up to 20 weeks

Collaborators and Investigators

• Sponsor: Indiana University
• Collaborators: State University of New York at Buffalo

Publications and helpful links

General Publications

• Hess HW, Tarr ML, Baker TB, Hostler D, Schlader ZJ. Ad libitum drinking prevents dehydration during physical work in the heat when adhering to occupational heat stress recommendations. Temperature (Austin). 2022 Jul 20;9(3):292-302. doi: 10.1080/23328940.2022.2094160. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Actual): May 4, 2023
• Study Completion (Actual): May 4, 2023

Study Registration Dates

• First Submitted: February 17, 2021
• First Submitted That Met QC Criteria: February 19, 2021
• First Posted (Actual): February 23, 2021

Study Record Updates

• Last Update Posted (Estimated): November 8, 2023
• Last Update Submitted That Met QC Criteria: November 6, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Wounds and Injuries; Body Temperature Changes; Heat Stress Disorders; Water-Electrolyte Imbalance; Hyperthermia; Dehydration
• Other Study ID Numbers: 1902420140

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No