The consequences of environment-induced heat stress on the kidney in female mice

Environment-induced heat stress (EIHS) is caused by a sustained elevation in body temperature, due to prolonged exposure to excess heat and humidity. Given the present and increasing frequency of EIHS and the gap in knowledge regarding EIHS-mediated impacts to the kidney, the purpose of this investigation was to determine the extent to which EIHS alters kidney health. We hypothesized EIHS would cause kidney injury and cellular dysfunction. To test this hypothesis, 7 wk old C57 female mice were assigned to either EIHS (n=14; 36.7 ± 0.16 °C, 36.3 ± 0.5 % humidity) or thermoneutral (TN) conditions (n=12, 31.2 ± 1.01 °C, 35 ± 0.7% humidity) for 24 h, kidneys were removed, weighed, and were either fixed for histology or frozen for biochemical measures. Environment-induced HS increased rectal temperature by 2.1 °C (p< 0.001), decreased body weight by 10% (p=0.03), and decreased absolute kidney weight (10%; p=0.02) compared to TN. Environment-induced HS increased relative protein abundance of heat shock proteins 70 (48%, p<0.01), 90 (37%, p<0.01), and 60 (36%, p=0.02), as well as heat shock factor 1 (2-fold, p=0.02) compared to TN. Histological inspection revealed EIHS animals had increased vacuolation in the proximal convoluted tubules (p<0.01) compared to TN animals. Using a western blot approach, we measured biomarkers of kidney tubular health and discovered EIHS increased protein abundance of NGAL (88%, p<0.01), IL-10 (36%, p=0.05), IL-6 (46%, p<0.01), MCP-1 (74%, p=0.04), and L-FABP (99%, p<0.01), which are suggestive of kidney injury. Environment-induced HS increased markers of inflammatory signaling including TLR4 (44%, p=0.04), phosphorylated (p-) NFκB (93%, p<0.01), p-JNK (54 kD; 51%, p=0.02), p-JNK (46 kD, 35%, p=0.02), AP-1 (33%, p=0.02), and TNFα (39%, p=0.05). Endoplasmic reticulum stress was increased by EIHS as Bip, p-IRE1α, Perk, XBP1s, ATF4, and CHOP were increased 27-190% (p<0.05-0.01) compared to TN animals. Markers of mitochondrial abundance remained similar between groups; however, EIHS may alter mitochondrial fusion and fission as Opa1 (71%, p=0.01), MFN2 (29%, p=0.04) and DRP1 (59%, p=0.04) were increased compared to TN; however, MFN1, FIS1, and p-DRP1 were similar between groups. Collectively, these data suggest that 24 h of EIHS causes kidney injury, but may also be suffcient to initiate changes that contribute to acclimation. This study was supported by USDA 2020-02716. This is the full abstract presented at the American Physiology Summit 2024 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.