Heat Acclimation Increases the Sensitivity of Biomarkers of Kidney Function to Hyperthermia during Exercise Heat Stress

INTRODUCTION: Hyperthermia during strenuous work in hot environments can transiently reduce kidney function. Heat acclimation is characterized by reduced thermal strain and increased sweating that may modify the response of biomarkers of kidney function to exercise heat stress. OBJECTIVE: We performed a secondary analysis to test the hypothesis that heat acclimation attenuates increases in circulating biomarkers of kidney function during exercise heat stress. METHODS: Eighteen young, healthy adults (13F; Age: 24±5 y; Height: 167.9±10.7 cm; Body mass: 73.0±14.0 kg) completed 10 days of treadmill walking (5 kph, 2% grade) for 120 min in a climatic chamber (40°C air temperature and 40% relative humidity with ~4.8 kph air velocity) to induce heat acclimation. Participants were euhydrated prior to exercise and drank 200 mL water every 20 min during exercise. Successful induction of heat acclimation was confirmed via attenuated increases in core temperature (ΔTc, telemetry pill) and greater whole body sweat rate (WBSR, changes in nude body mass corrected to fluid consumption and urine output) during exercise heat stress on day 10 (D10) vs. day 1 (D1). Kidney function was assessed as the change in serum creatinine from pre-to-post exercise (∆Cr). Plasma neutrophil gelatinase-associated lipocalin (∆NGAL) was measured from pre-to-post exercise to estimate the magnitude of renal hypoxemia. Statistical comparisons were made between heat acclimated (D10) and unacclimated (D1) with paired t-tests. Pearson product correlations on D1 and D10 were used to determine the relation between hyperthermia and kidney function (i.e., ΔTc vs. ∆Cr) and the relation between renal hypoxemia as a mechanism for reduced kidney function (i.e., ΔNGAL vs. ∆Cr). Significant differences between correlation coefficients D10 vs. D1 were assessed by Meng’s Z-test to examine the effect of heat acclimation on these relations. Data are reported as mean±SD. RESULTS: The increase in ΔTc was attenuated on D10 vs. D1 (1.16±0.43 vs. 1.56±0.54°C, p<0.001) and WBSR was higher on D10 vs. D1 (0.8±0.2 vs. 0.7±0.2 L/h, p=0.004). ΔCr (D10: 0.1±0.1 mg/dl; D1: 0.1 ± 0.1 ng/ml, p=0.20) and ∆NGAL (D10: 16.4±8.1 ng/ml; D1: 17.3±7.7 ng/ml, p=0.66) did not differ between days. The correlation between ΔTc and ΔCr was greater (p=0.03) on D10 (r=0.61, p=0.004) vs. D1 (r=-0.07, p=0.91). There was no difference in the correlation between ΔNGAL and ΔCr (P=0.51) on D10 (r=0.53, p=0.021) vs. D1 (r=0.41, p=0.08). CONCLUSION: These findings suggest that heat acclimation status does not alter the magnitude of increase in circulating biomarkers of kidney function following exercise heat stress. However, that ΔCr was correlated with ΔTc on D10 but not D1 suggests that the kidneys may exhibit increased sensitivity to hyperthermia in heat acclimated individuals. These findings suggest that this response may not be mediated by renal hypoxemia, as there was no difference in the relation between ΔNGAL and ΔTc on D10 vs. D1. These data provide novel insight into the contribution of hyperthermia during exercise in the heat to kidney injury in heat acclimated individuals. Funded by USAMRDC/MOMRP. Author views not representative of the Army/DOD. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.