Acute Kidney Injury and Ultra-endurance Running

Overview

This study aims to understand how participating in the Western States Endurance Run (WSER), a 100-mile ultramarathon, affects kidney health. Long, strenuous exercise in hot conditions can temporarily strain the kidneys, especially when combined with dehydration, muscle breakdown, and the use of common pain-relief medications such as ibuprofen. Although kidney stress has been reported in endurance sports, no study has examined it directly in runners during the WSER using newer, more sensitive urine markers of kidney injury. Runners who volunteer will complete brief assessments before and after the race. These include providing a urine sample, a small finger-prick blood sample, a body-weight measurement, and answering a short questionnaire about pain-medication use. During the race, participants will wear a global positioning system (GPS) watch and heart-rate strap to monitor effort. Each assessment takes about 15 minutes, and no follow-up is required. Findings from this study will help determine how often kidney stress occurs in this event and what factors may contribute to it, ultimately supporting safer training and medical practices for ultramarathon athletes.

The study is a single-group, pre- and post-test design where participants will be assessed prior to the start of the WSER, upon completion of the race and 24 hours post-race. Approximately one hour prior to the race commencing, participants will be asked to void the entire contents of their bladder in a urine container in order to measure urine volume, flow rate and urine specific gravity (USG) to assess hydration status and for subsequent analysis of acute kidney injury (AKI) risk (insulin-like growth factor-binding protein 7 (IGFBP7), tissue inhibitor of metalloproteinase 2 (TIMP-2), and neutrophil gelatinase-associated lipocalin (NGAL)). Participants will also be provided a Garmin 945 GPS watch and a wearable device (i.e., the HRM-PRO Run Dynamics strap) for the race. The system is a waterproof heartrate monitor strap with an embedded accelerometer that quantifies gait metrics (ground reaction force). At this time they will also have their weight measured, and complete a short questionnaire to document any recent intake of non-steroidal anti-inflammatory (NSAIDS) medication. Lastly, the research team will collect a small capillary sample (\~ 300 microliters) of whole blood into a heparinised tube and immediately analyse the sample for creatinine (CR) and blood urea nitrogen (BUN) using a portable, point of care analyzer (i-STAT 1 Wireless, Abbott, Princeton). Upon completing the WSER, participants will again be asked to provide a urine sample (following the pre-race methodology), have their weight measured, complete the questionnaire regarding additional NSAID use during the race, and lastly a final capillary blood sample for post-race analysis of CR and BUN. Participants will then be randomized into one of two groups (sodium bicarbonate (SB) or placebo), with one receiving a pre-packaged standard amount of either 15, 19, or 22 grams of sodium bicarbonate provided by Maurten (Maurten Bicarb System, MaurtenTM, Göteborg, SWE) depending on their body weight. MaurtenTM will also provide an equivalent placebo product. Participants will be asked to consume the SB or placebo, which is delivered in a patented hydrogel system (similar to a yogurt). The urine and blood sampling procedure will be repeated 24 hours post-race at a location to be determined. All urine samples will be packed in an appropriately labeled biohazard container with cold packs, and brought back to the Arizona State University's Integrated Human Performance Lab (IHPL; Principle Investigator (PI)-Siegler) for measures of AKI risk with the research team. As per the Transportation Security Administration (TSA) regulations, biological specimens that are non-infectious and contain less than 30 mL of fluid in each container are permissible in checked baggage. The samples from each of the 3 races will be approximately 5 milliliters (mL) each subject (so estimated at 50 mL total for each of the 3 races). Methodological Techniques \& Measurements: Anthropometric Assessments (Descriptive Data) Participants will be asked to use the restroom to empty their bladder (this sample will be used for AKI biomarkers, urine volume and USG), after which measurements of height and body mass will be obtained. This measurement will occur pre- and post-race to estimate loss of body weight (e.g., dehydration). Urine Volume and Specific Gravity (USG) Participants will be asked to void into graduated measuring containers (\~ 900 mL), which will subsequently be used to calculate total urine volume pre-, post-race, and 24 hours post-race and normalize AKI markers. Once volume is obtained, samples from this measurement will be used to assess dehydration (USG) and for subsequent analysis of AKI (see Kidney Injury Markers). USG will be measured using a handheld refractometer (Atago PALTMSeries, Tokyo, JP). Capillary Blood Draws Capillary blood (\~ 300 microliters; 600 total) will be obtained from an index finger pre-, post-race and 24 hours post-race to measure creatinine (CR) and blood urea nitrogen (BUN) using a portable, point of care analyzer (i-STAT 1 Wireless, Abbott, Princeton). Kidney Injury Markers AKI risk will be assessed using Enzyme-Linked Immunosorbent Assay (ELISA) kits to measure concentrations of insulin-like growth factor-binding protein 7 (IGFBP7) (RayBiotech Life, Peachtree Corners, GA), tissue inhibitor of metalloproteinase 2 (TIMP-2) (RayBiotech Life, Peachtree Corners, GA), and neutrophil gelatinase-associated lipocalin (NGAL) (Enzo Life Sciences, Farmingdale, NY). Urine samples will be centrifuged before analysis and resultant supernatant used for analyses. The kidney markers will be normalized to urine flow rate, considering changes in the urine production that may happen in dehydration conditions such as exercise in the heat. All ELISA analyses will be completed according to manufacturer guidelines. Heart Rate and Activity Profile Participants will wear a chest-mounted heart rate monitor (Garmin HRM-PRO Run Dynamics strap) during the race. The device consists of an elastic strap with an embedded sensor that is worn directly against the skin, positioned horizontally around the chest, just below the pectoral muscles (breastbone), in accordance with manufacturer instructions. Prior to the race, a trained member of the research team will demonstrate proper placement and fit of the heart rate strap. Participants will be instructed to ensure the strap fits snugly but comfortably, allowing normal breathing and movement without excessive tightness. The strap does not deliver electrical stimulation or vibration; it passively records heart rate and movement data. Participants may adjust or remove the heart rate strap at any time during the race if they experience discomfort, skin irritation, or any other concern. Removal of the strap will not affect continued participation in the study or result in penalty. Heart rate (HR) and activity rates (via accelerometer measurements) will be measured continuously (1 hertz (Hz)) during the race with participants wearing a Garmin 945 GPS watch and a wearable device (i.e., the HRM-PRO Run Dynamics strap). NSAID Questionnaire During the pre-race data collection period, participants will be asked if they have consumed any non-steroidal anti-inflammatory drugs prior to the start of the race (quantity and type (e.g., ibuprofen)). Once the race is completed, the same questionnaire will be used to ask participants if they consumed any NSAIDs during the race, and at what quantity.