The Effect of Manipulating Hydration Status During Cycling in the Heat on Acute Kidney Injury Biomarkers

Study Overview
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Brief Summary
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Acute Kidney Injury (AKI) is common in prolonged endurance events. Risk factors for exercise-associated AKI include: the exercise itself, heat, hypohydration, muscle breakdown and non-steroidal anti-inflammatory drug (NSAID) use. Prior research from our laboratory showed the hypohydration during high-intensity running increased a biomarker of AKI (urine osmolality-corrected kidney injury molecule 1). Therefore, the current study will now investigate the effect of manipulating hydration status during cycling on biomarkers of AKI.

Official Title
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The Effect of Hypohydration During Cycling in the Heat on Acute Kidney Injury Biomarkers

Conditions
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Hypohydrated, Euhydrated

Intervention / Treatment
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* Other: Water intake


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy recreationally active Exclusion Criteria: Smoker/vaper regular use of anti-inflammatory medications (e.g. ibuprofen) history of kidney disease or diabetes

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

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: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hypohydrated<br>Participants will be required to restrict their water intake during cycling in the heat (90-120 minutes at 35°C), in order to achieve a body mass loss of approximately 3%. | Other: Water intake<br>* Water intake will be manipulated in both arms to create a hypohydrated state and a euhydrated state, post-exercise<br>|
| Experimental: Euhydrated<br>Participants will be provided with water intake that matches their sweat losses during cycling in the heat (90-120 minutes at 35°C) | Other: Water intake<br>* Water intake will be manipulated in both arms to create a hypohydrated state and a euhydrated state, post-exercise<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in urinary Kidney Injury Molecule 1 (uKIM-1) (uncorrected/raw values and urine osmolality-corrected values) | A novel protein biomarker for acute kidney injury | Pre-exercise (baseline), post-exercise (immediately after the intervention), 24 hours post-baseline | 
| Changes in urinary neutrophil gelatinase-associated lipocalin (uNGAL) (uncorrected/raw values and urine osmolality-corrected values) | A novel protein biomarker for acute kidney injury | Pre-exercise (baseline), post-exercise (immediately after the intervention), 24 hours post-baseline | 
| Changes in urine osmolality | A measure of urine concentration. | Pre-exercise (baseline) and post-exercise (immediately after the intervention), as well as all urine produced from post-exercise until 24 hours post-baseline | 
| Changes in serum creatinine | Serum creatinine is a marker of kidney function | Pre-exercise (baseline), post-exercise (immediately post-exercise), 24 hours post-baseline | 
| Incidence of Acute Kidney Injury (as determined by changes in serum creatinine) | A rise in serum creatinine of 1.5 fold or more from baseline will be defined as acute kidney injury | Pre-exercise (baseline), post-exercise (immediately post-exercise), 24 hours post-baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma volume changes |  | Pre-exercise (baseline), post-exercise (immediately after the intervention), 24 hours post-baseline | 
| Changes in serum osmolality | The gold standard marker of hydration status | Pre-exercise (baseline), post-exercise (immediately after the intervention), 24 hours post-baseline | 
| Body mass changes |  | pre-exercise (baseline), throughout exercise, post-exercise (immediately after the intervention), 24 hours post-baseline | 
| Changes in creatine kinase | A marker of muscle damage | Pre-exercise (baseline), post-exercise (immediately after the intervention), 24 hours post-baseline | 
| Changes in lactate dehydrogenase | A marker of muscle damage | Pre-exercise (baseline), post-exercise (immediately after the intervention), 24 hours post-baseline | 
| Ad libitum energy (Kj), carbohydrate (g), sugar (g), protein (g), fat (g), saturated fat (g), sodium (g) and water intake (g). | Participants will complete a weighed food and fluid diary, using a set of food scales and a diary, to record all food and fluid that they ingest. This data will then be analysed using dietary analysis software (e.g. Nutritics) | from post-exercise (immediately after the intervention) until 24 hours post-baseline | 
| Changes in headache scores | Participants will be asked to rate their headache on a scale of 0-10, with higher scores meaning a worse outcome . | pre-exercise (baseline), every 30 minutes during exercise (30, 60,90 and 120 minutes), post-exercise (immediately after the intervention) and 24 hours post-baseline | 
| Changes in nausea scores | Participants will be asked to rate their nausea on a scale of 0-10, with higher scores meaning a worse outcome . | pre-exercise (baseline), every 30 minutes during exercise (30, 60,90 and 120 minutes), post-exercise (immediately after the intervention) and 24 hours post-baseline | 
| Changes in dizziness scores | Participants will be asked to rate their dizziness on a scale of 0-10, with higher scores meaning a worse outcome . | pre-exercise (baseline), every 30 minutes during exercise (30, 60,90 and 120 minutes), post-exercise (immediately after the intervention) and 24 hours post-baseline | 
| Changes in thirst scores | Participants will be asked to rate their thirst on a scale of 0-10, with higher scores meaning a worse outcome . | pre-exercise (baseline), every 30 minutes during exercise (30, 60,90 and 120 minutes), post-exercise (immediately after the intervention) and 24 hours post-baseline | 
| Changes in thermal comfort scores | Participants will be asked to rate their thermal comfort on a scale of -10 to 10, with -10 being cold impossible to bear and 10 being heat impossible to bear | pre-exercise (baseline), every 30 minutes during exercise (30, 60,90 and 120 minutes), post-exercise (immediately after the intervention) and 24 hours post-baseline | 
| Changes in gastrointestinal comfort scores | Participants will be asked to rate their gastrointestinal comfort on a scale of 0-10, with higher scores meaning a worse outcome . | pre-exercise (baseline), every 30 minutes during exercise (30, 60,90 and 120 minutes), post-exercise (immediately after the intervention) and 24 hours post-baseline | 
| Changes in stomach fullness scores | Participants will be asked to rate their stomach fullness on a scale of 0-10, with higher scores meaning a worse outcome . | pre-exercise (baseline), every 30 minutes during exercise (30, 60,90 and 120 minutes), post-exercise (immediately after the intervention) and 24 hours post-baseline | 
| Changes in stomach bloatedness scores | Participants will be asked to rate their stomach bloatedness on a scale of 0-10, with higher scores meaning a worse outcome . | pre-exercise (baseline), every 30 minutes during exercise (30, 60,90 and 120 minutes), post-exercise (immediately after the intervention) and 24 hours post-baseline | 
| Changes in urge to vomit scores | Participants will be asked to rate their urge to vomit on a scale of 0-10, with higher scores meaning a worse outcome . | pre-exercise (baseline), every 30 minutes during exercise (30, 60,90 and 120 minutes), post-exercise (immediately after the intervention) and 24 hours post-baseline | 
| Changes in urinary creatinine |  | pre-exercise (baseline), post-exercise (immediately after the intervention) and 24 hours post-baseline | 
| Changes in heart rate | Provides insight into exercise intensity | Will be monitored throughout the exercise intervention, at 15 minute intervals (15 minutes, 30 minutes, 45 minutes, 60 minutes, 75 minutes, 90 minutes, 105 minutes and 120 minutes) | 
| changes in rating of perceived exertion | Provides insight into exercise intensity | Will be monitored throughout the exercise intervention, at 30 minute intervals (30 minutes, 60 minutes, 90 minutes and 120 minutes) | 
| Changes in aural temperature | in-ear temperature | Will be determined immediately prior to the exercise intervention (at rest) and then throughout the exercise intervention at 15 minute intervals (15 minutes, 30 minutes, 45 minutes, 60 minutes, 75 minutes, 90 minutes, 105 minutes and 120 minutes) |