Greater renal interstitial expansion and inflammation in older male versus older female rats following a four-day simulated heatwave

Abstract

Acute kidney injury (AKI) is an emerging cause of morbidity during heatwaves worldwide and is associated with negative health outcomes. Older age increases the likelihood of AKI, which is a top cause of hospitalization during heatwaves in older adults. Further, biological sex likely affects the severity of, and prognosis following, AKI. Moreover, recent observations suggest that older women are at greater risk of AKI during heatwaves compared to older men. Whether this observation can be directly attributed to biological sex is unclear. Therefore, we tested the hypothesis that older female rats experience more severe kidney injury during a four-day simulated heatwave, compared to older male rats.To test this hypothesis, older (18-22 month old) male (M) and female (F) Wistar rats were exposed to a 36°C (M: n=5; F: n=8) or a 21°C (M: n=2; F: n=2) environment for three hours over four consecutive days. During, and for five hours following heat exposure, the rats did not have access to food or water, but otherwise were housed in standard housing conditions with free access to food and water. Core temperature (Tc) was continuously monitored and rats were removed from the heat if Tc reached 40.5℃, a safeguard put in place to prevent heatstroke. Data are presented as mean±SD.Male and females did not differ in the amount of time exposed to heat during each day (average duration - M: 39.3±4.0, F: 42.3±5.2 minutes, P=0.86) or body weight loss during heat exposure (average body weight loss - M: -2.0±0.1, F: -2.5±0.1% P=0.93). Serum creatinine concentration did not differ between heat exposed males and females on Day 1 (pre- M: 0.4±0.2, F: 0.4±0.1; post- M: 0.5±0.2, F: 0.4±0.2 mg/dL) or Day 4 (post- M: 0.4±0.1, F:0.3±0.1 mg/dL; P=0.86) Heat exposure resulted in cortical interstitial expansion and immune cell infiltration in aged male, but not female rats (M Heat: 77.2±36.1, F Heat: 12.1±16.5, M Control: 18.2±17.5, F Control: 13.4±19.0 dots per image, P=0.002). Only older male rats displayed greater interstitial immune cell infiltration than older controls in response to heating (P=0.04). Immunohistochemistry demonstrated distinct populations of CD3e+ T cells, CD20+ B cells and CD68+ macrophages within the interstitial immune cell infiltration in the older male rats. Kidney expression of kidney injury molecule 1 (KIM1, P=0.41) and neutrophil gelatinase associated lipocalin (NGAL, P=0.12) did not differ between older male and female rats exposed to heat or control conditions. Compared to older female rats, older male rats display increased cortical interstitial expansion and inflammation following a four-day simulated heatwave. UL1TR002529, T32DK120524 This is the full abstract presented at the American Physiology Summit 2023 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.