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

Vliora M, McCormick JJ, King KE, Gkiata P, Kaltsatou A, Flouris AD, Kenny GP. Brief extreme passive heat exposure leads to elevated biomarkers of systemic inflammation and acute kidney injury in older vs young adults. Eur J Appl Physiol. 2025 Jun 23. doi: 10.1007/s00421-025-05827-w. Epub ahead of print. PMID: 40549207.

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.

Full Text Link: https://pubmed.ncbi.nlm.nih.gov/40549207/