The effect of manipulating fluid intake on biomarkers of renal injury

Acute kidney injury (AKI; diagnosed using changes in serum creatinine) can occur following prolonged endurance events, with incidence ranging from 4-85%. However, these reported incidences are likely often an overestimate due to use of serum creatinine concentrations to diagnose AKI following exercise having significant limitations, as serum creatinine concentrations can be increased due to muscle damage (i.e., increased production) or a benign reduction in renal blood flow (i.e., reduced clearance). Nonetheless, post-exercise increases in more appropriate novel biomarkers of renal tubular injury, such as urinary neutrophil gelatinase-associated lipocalin (uNGAL) and urinary kidney injury molecule-1 (uKIM-1), have also been documented. The increases in these biomarkers of renal tubular injury post-exercise were likely due to a combination of several factors, of which hypohydration is likely the easiest to modify. furthermore, there is evidence to suggest that water ingestion may be able to attenuate biomarkers of renal injury via multiple mechanisms. Therefore, the main aim of the present thesis was to investigate the effect of manipulating fluid intake on uNGAL and uKIM-1 concentrations.The responses of uNGAL and uKIM-1 concentrations to high-intensity intermittent running (as seen in team sports) were previously unknown. Therefore, Chapter 2 aimed to investigate the effect of manipulating water intake during high-intensity intermittent running on uNGAL and uKIM-1 concentrations. Chapter 2 utilised a modified Loughborough Intermittent Shuttle Test Protocol, involving 6, 15 min blocks of shuttle running. Post-exercise, osmolality-corrected uNGAL and uKIM-1 concentrations were increased compared to pre-exercise, with osmolality-corrected uKIM-1 concentrations greater in the fluid restriction (FR) trial than the control (C) trial (FR: 2.76 [1.72-4.65] ng/mOsm; C: 1.94 [1.10-2.54] ng/mOsm; P = 0.003; median [interquartile range]). These findings indicated that replacing the majority of sweat losses with water ingestion attenuated post-exercise increases of biomarkers of renal injury.Chapter 3 aimed to determine if manipulating water intake during moderate-intensity cycling in the heat (lasting up to 2 h) affected uNGAL and uKIM-1 concentrations, showing that fluid restriction increased osmolality-corrected uNGAL (when expressed as percentage changes from baseline; FR: 61 [17-141] %, C: 7.1 [-4-24] %; P = 0.033) and uKIM-1 concentrations (FR: 2.74 [1.87-5.44] ng/mOsm, C: 1.15 [0.84-2.37] ng/mOsm; P = 0.024) thirty minutes post-exercise (compared to when body mass losses were fully replaced with water ingestion). These findings suggest that fully replacing body mass losses with water ingestion during exercise attenuates biomarkers of renal injury, regardless of exercise-intensity or the degree of muscle damage produced.Chapter 4 investigated the effect of 24 h fluid restriction, in the absence of exercise, showing that fluid restriction resulted in greater concentrations of osmolality-corrected uKIM-1 after 12 (FR: 1.097 ± 0.587 ng/mOsm, C: 0.570 ± 0.408 ng/mOsm; P < 0.001) and 24 hours (FR: 1.932 ± 1.173 ng/mOsm, C: 1.599 ± 1.012 ng/mOsm; P = 0.01), compared to when subjects consumed 40 mL/kg body mass of water.Whilst fructose ingestion may increase renal injury, the evidence for this primarily comes from studies where fructose was ingested in the form of a sweetened beverage. However, it could be hypothesised that ingesting fructose in its natural form (for example, in fruit) may not produce this effect, as the antioxidants found in natural sources of fructose may attenuate increases in biomarkers of renal injury by attenuating oxidative stress. Additionally, the responses of uNGAL and uKIM-1 to running a half-marathon were unknown. Therefore, Chapter 5 investigated the effect of manipulating the source of fructose (natural vs crystalline) consumed during a half-marathon run on uNGAL and uKIM-1 concentrations. Osmolality-corrected uNGAL and uKIM-1 concentrations were not different between trials.From this thesis, it can be concluded that fluid restriction, in both exercising and non-exercising contexts, increases biomarkers of renal injury. However, manipulating the source of fructose consumed during a half-marathon run does not appear to influence biomarkers of renal injury.