Impact of extreme heat exposure on acute kidney injury risk in older adults living with heart disease

Background: Acute kidney injury (AKI) is a leading cause of heat-related hospitalizations in older adults. Epidemiological evidence shows that older adults living with cardiovascular disease face an increased risk of morbidity and mortality during extreme heat events. Although the renal and cardiovascular systems are closely interconnected, it remains unknown whether extreme heat exposure elevates AKI risk in this population. Objective: To characterize AKI risk responses to extreme heat exposure in older adults living with coronary artery disease (CAD). Methods: Eighteen adults (67 ± 9 y; 2 females) with an angiographic history of CAD participated in this study. Participants completed two 3-hour passive exposures in an environmental chamber on separate days: very hot/dry (HD, 45 ± 0°C, 15 ± 2% relative humidity) and hot/humid (HH, 39 ± 0°C, 62 ± 3% relative humidity). Participants remained seated and drank 3 mL/kg body mass of water every hour. Rectal temperature (Tre) was continuously recorded. Body mass loss was calculated from changes in nude body mass. Pre- and post-exposure urine and blood samples were analyzed for serum creatinine, urine creatinine, urine osmolality, and AKI risk biomarkers including urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor metalloproteinase 2 (TIMP2), both normalized to urine osmolality. The product of each marker (IGFBP7×TIMP2) was used as the primary measure of AKI risk. Results: Very Hot/Dry (HD) Exposure: Tre increased by 0.4 ± 0.4°C (p < 0.01) and body mass loss was 0.6 ± 0.3%. Kidney function markers showed increases: serum creatinine (+0.06 ± 0.05 mg/dL, p < 0.001) and urine creatinine (+48 ± 62 mg/dL, p = 0.01), while changes in urine osmolality were not significant (+81 ± 226 mOsm/kg, p = 0.09). AKI biomarkers increased: IGFBP7×TIMP2 by 0.22±0.38 (ng/mL) 2 /1000 (p = 0.02), IGFBP7/uOsm by 0.05 ± 0.05 (ng/mL)/(mOsm/kg) (p < 0.01), and TIMP2/uOsm by 0.0019 ± 0.0020 (ng/mL)/(mOsm/kg) (p < 0.01). Hot/Humid (HH) Exposure: Tre increased by 0.4 ± 0.2°C (p < 0.01) and body mass loss was 0.2 ± 0.2%. Kidney function markers showed no changes: serum creatinine (-0.01 ± 0.09 mg/dL, p = 0.29), urine creatinine (+14 ± 72 mg/dL, p. =0.64), and urine osmolality (-40 ± 298 mOsm/kg, p = 0.65). AKI biomarkers also remained unchanged: IGFBP7×TIMP2 (+0.08 ± 0.63 (ng/mL) 2 /1000, p = 0.45), IGFBP7/uOsm (+0.02 ± 0.10 (ng/mL)/(mOsm/kg), p = 0.33), and TIMP2/uOsm (+0.0014 ± 0.0025 (ng/mL)/(mOsm/kg), p = 0.07). Conclusions: While kidney function and AKI risk biomarkers were unchanged in HH, changes in these markers were observed following HD in older adults with CAD. These data demonstrate that extreme heat exposure may elicit early renal stress in older adults with CAD, which may depend on environmental conditions and modest differences in dehydration. Future studies should investigate mechanisms underlying the biomarker responses and determine whether longer or repeated heat exposures further increase AKI risk. Support: National Institute for Occupational Safety and Health (R01OH011528); National Institute of Health (R01DK144492); National Health and Medical Research Council of Australia (GNT1147789) This abstract was presented at the American Physiology Summit 2026 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.