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. 2025 Dec;125(12):3631-3639.
doi: 10.1007/s00421-025-05827-w. Epub 2025 Jun 23.

Brief extreme passive heat exposure leads to elevated biomarkers of systemic inflammation and acute kidney injury in older vs young adults

Maria Vliora #  1 , James J McCormick #  2 , Kelli E King  2 , Paraskevi Gkiata  1 , Antonia Kaltsatou  1 , Andreas D Flouris  1 , Glen P Kenny  3
Affiliations

Brief extreme passive heat exposure leads to elevated biomarkers of systemic inflammation and acute kidney injury in older vs young adults

Maria Vliora et al. Eur J Appl Physiol. 2025 Dec.

Abstract

Purpose: With the advent of climate change, older adults are increasingly exposed to hot ambient temperatures that can lead to a state of heat-induced cytotoxicity contributing to heat-vulnerability. We assessed changes in serum proteins associated with indices of cellular stress in young and older adults exposed to extreme passive heat exposure.

Methods: Responses were assessed in 19 young (23 ± 2.9 years; 5 female) and 27 older (62 ± 7.0 years; 2 female) adults exposed to a 3-h seated passive extreme heat exposure (44 °C, 30% relative humidity). Serum samples were assessed before and after heat exposure for proteins indicative of systemic inflammation (CRP, sCD14, TNF-α, and IL-6), intestinal permeability (IFABP), acute kidney injury (NGAL), and cytoprotection (irisin, klotho, and HSP70) via enzyme-linked immunosorbent assays.

Results: The older group displayed significant elevations in CRP (18.06 ± 20.3 vs 24.3 ± 25.0 mg/mL, p < 0.002) in response to heat exposure that was not observed in the young group (both p > 0.999) although no changes in sCD14, TNF-α, or IL-6 occurred in either group. However, significant elevations in NGAL concentrations from baseline were observed in the older group (17.74 ± 23.65 vs 40.75 ± 58.18 ng/mL, p = 0.001), with no changes from baseline in the young group (p = 0.999). Conversely, klotho was significantly elevated after heat exposure in the young group (1346.37 ± 2242.49 vs 1129 ± 202 pg/mL, p = 0.017) but not in older adults (p > 0.999).

Conclusion: Taken together, older adults experienced some evidence of elevated inflammatory signaling and acute kidney injury that is accompanied by a blunted klotho response to extreme heat.

Keywords: Acute kidney injury; Aging; Cellular stress response; Extreme heat; Heat shock protein; Heatwaves; Inflammation; Intestinal permeability.

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