Biomarkers to Assess Acute Kidney Injury Risk During Heat Strain

Prolonged, high intensity work in a hot environment results in significant strain on the body, known as heat strain. Heat strain in hot occupational settings such as agriculture, fire suppression, and military work can lead to ~20% of workers exceeding the glomerular filtration rate indicated thresholds for acute kidney injury (AKI). However, it is unclear whether these individuals truly experienced AKI or if these were normal, healthy physiologic responses. To better determine if AKI occurs in the staggering number of workers previously reported, AKI biomarkers are needed in addition to kidney function markers (e.g., glomerular filtration rate) to characterize this response. The product of urinary tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) is a promising Food and Drug Administration approved biomarker indicating risk of AKI and is currently used in hospitalized individuals. The usefulness of this biomarker in determining AKI in healthy individuals during heat strain is now beginning to be understood. Consecutive days of heat strain can result in repeated AKI, which is hypothesized to lead to chronic kidney disease. There is an epidemic of chronic kidney disease of non-traditional causes occurring in workers who undergo repeated days heat strain, including approximately 15% of outdoor workers in Central America. Of the few studies that investigated consecutive days of work in the heat, we demonstrated that participants exceed the glomerular filtration rate indicated threshold for AKI during consecutive days of heat strain. This project will determine whether [TIMP-2 x IGFBP7] increases during occupational relevant heat exposures in a healthy, active population. Additionally, this project will compare the impact of repeated exposures to a hot environment on risk of AKI.

Study Overview

• Status: Recruiting
• Conditions: Hyperthermia; Kidney Injury, Acute
• Intervention / Treatment: Other: Work Protocol

• Study Type: Interventional
• Enrollment (Anticipated): 16
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Riana R Pryor, PhD; Phone Number: 7163489306; Email: rpryor@buffalo.edu

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14214
      • Recruiting
      • Center for Research and Education in Special Environments
      • Contact: Jocelyn Stooks, MPH; Phone Number: 716-829-5455; Email: jstooks@buffalo.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 39 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy individuals (18-39 years old)
• Regularly completes aerobic exercise at least 60 min per week

Exclusion Criteria:

• History of cardiovascular, metabolic, respiratory, neural, or renal disease
• Hypertensive or tachycardic during the screening visit (systolic blood pressure > 139 mmHg, diastolic blood pressure > 89 mmHg, heart rate > 100 bpm)
• Current tobacco or nicotine use or previous regular use within the past 2 years
• Current or previous musculoskeletal injury limiting physical activity
• Taking medications with known thermoregulatory or cardiovascular effects (e.g., aspirin, beta blockers, diuretics, psychotropics, etc.)
• A positive pregnancy test at any point during the study or currently breastfeeding
• Study physician discretion based on any other medical condition or medication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Work Heat Stress; Each participant will complete three consecutive days of heavy intensity aerobic work in a hot environment.	Other: Work Protocol; Participants will complete 4 hours of walking and cycling to a work:rest ratio of 3:1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
[TIMP-2 x IGFBP-7] concentration	The product of [Tissue inhibitor of metalloproteinase 2 (TIMP-2) and Insulin-like growth factor binding protein 7 (IGFBP7)] is a biomarker that has the potential for prediction of acute kidney injury.	Minute 0
[TIMP-2 x IGFBP-7] concentration	The product of [Tissue inhibitor of metalloproteinase 2 (TIMP-2) and Insulin-like growth factor binding protein 7 (IGFBP7)] is a biomarker that has the potential for prediction of acute kidney injury.	Hour 4
[TIMP-2 x IGFBP-7] concentration	The product of [Tissue inhibitor of metalloproteinase 2 (TIMP-2) and Insulin-like growth factor binding protein 7 (IGFBP7)] is a biomarker that has the potential for prediction of acute kidney injury.	Hour 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NGAL concentration	Neutrophil gelatinase-associated lipocalin (NGAL) measures kidney injury.	Minute 0
NGAL concentration	Neutrophil gelatinase-associated lipocalin (NGAL) measures kidney injury.	Hour 4
NGAL concentration	Neutrophil gelatinase-associated lipocalin (NGAL) measures kidney injury.	Hour 5
Serum creatinine concentration	Serum creatinine concentration is a measure of kidney function.	Minute 0
Serum creatinine concentration	Serum creatinine concentration is a measure of kidney function.	Hour 4
Serum creatinine concentration	Serum creatinine concentration is a measure of kidney function.	Hour 5
Urine creatinine concentration	Urine creatinine concentration is a measure of kidney function.	Minute 0
Urine creatinine concentration	Urine creatinine concentration is a measure of kidney function.	Hour 4
Urine creatinine concentration	Urine creatinine concentration is a measure of kidney function.	Hour 5

Collaborators and Investigators

• Sponsor: State University of New York at Buffalo

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 13, 2022
• Primary Completion (ANTICIPATED): December 1, 2023
• Study Completion (ANTICIPATED): December 1, 2023

Study Registration Dates

• First Submitted: January 18, 2023
• First Submitted That Met QC Criteria: January 26, 2023
• First Posted (ACTUAL): February 2, 2023

Study Record Updates

• Last Update Posted (ACTUAL): February 2, 2023
• Last Update Submitted That Met QC Criteria: January 26, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Body Temperature Changes; Heat Stress Disorders; Wounds and Injuries; Acute Kidney Injury; Hyperthermia
• Other Study ID Numbers: STUDY00005847-Pilot

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Once published, pooled and de-identified data will be made available to interested researchers upon request.

Drug and device information, study documents

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