Ad Libitum Drinking Does Not Modify Renal Oxidative Stress or Inflammation During Simulated Occupational Heat Stress

Abstract

Prolonged heat exposure increases acute kidney injury (AKI) risk likely due to renal oxidative stress and inflammation. However, the effect of occupational heat stress (OHS) and the modifying role of hydration on renal oxidative stress and inflammation is unknown. This study tested the hypothesis that compared to fluid restriction ad libitum drinking consistent with OHS recommendations will attenuate renal oxidative stress and inflammation during simulated OHS. In a randomized, crossover design, 13 healthy adults (5 women) completed two 2 h OHS simulations consisting of of 8 circuits of treadmill walking (10 min) and rowing (5 min) at an oxygen uptake of 1.2 L/min in a wet bulb globe temperature of 33.1±0.2°C. In the drinking trial (Drink), subjects were provided 237 mL of a non-caloric sport drink (Gatorade Zero) every 15 min and drank ad libitum. In the fluid restriction trial (NoDrink), no fluid was provided. Rectal temperature and body weight were recorded. Urine and blood samples were collected pre-, post- and 1 h post- exposure. Inflammatory (monocyte chemotactic protein-1, MCP-1) and oxidative stress (thioredoxin 1, TRX-1) markers were measured in urine and serum, and fractional excretion (FE) was calculated. AKI risk was quantified as the product of urine insulin-like growth factor-binding protein 7 and urine tissue inhibitor of metalloproteinase 2 ([IGFBP7•TIMP-2]). Data are presented as mean ± SD. Peak rectal temperature was not different between trials (Drink: 38.5±0.4°C, NoDrink: 38.6±0.4°C, p=0.346). Percent changes in body weight were lower in Drink (1.3±0.8% vs. 2.8±0.9%, p<0.001). FETRX-1 was elevated at post- (0.50±0.00%) compared to pre- (0.36±0.00%, p=0.011) and 1 h post- (0.29±0.13%, p=0.011). FEMCP-1 was elevated at post- (1.25±0.18%) compared to pre- (1.02±0.17%, p=0.006) but not 1 h post- (1.27±0.03%, p>0.999). FETRX-1 and FEMCP-1 did not change significantly between trials (trial x time: p³0.622). [IGFBP7•TIMP-2] was higher at 1 h post- (17.5±1.0 (ng/mL)2/1000) compared to pre- (0.2±0.1 (ng/mL)2/1000, p<0.001) and post- (1.1±0.4 (ng/mL)2/1000, p<0.001) but did not differ between trials (trial x time: p=0.556). Peak changes in [IGFBP7•TIMP-2] were not significantly correlated with peak changes in FETRX-1 (r=0.126, p=0.557) or FEMCP-1 (r=0.292, p=0.166) and were correlated with peak changes in serum MCP-1 (r=0.714, p<0.001) but not serum TRX-1 (r=0.227, p=0.286). Two hours of simulated OHS increased renal inflammation (FEMCP-1), oxidative stress (FETRX-1), and AKI risk ([IGFBP7•TIMP-2]), while ad libitum drinking did not modify FEMCP-1, FETRX-1, or [IGFBP7•TIMP-2]. Lack of correlations between peak changes in [IGFBP7•TIMP-2] and FEMCP-1, FETRX-1, or serum TRX-1, but the strong positive correlation with peak serum MCP-1 suggests a role for systemic inflammation in OHS induced AKI risk. NCT05458843 Funding: R01OH011528. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.