Abstract: TH-PO0157
Simulated Heat Wave Promotes Increased Kidney Interstitial Inflammation and Tissue Damage in Aged Male Wistar Rats
Session Information
- AKI: Mechanisms - 1
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Lewis, Alexander, Indiana University School of Medicine, Indianapolis, Indiana, United States
- Collett, Jason Andrieu, Indiana University School of Medicine, Indianapolis, Indiana, United States
- Hato, Takashi, Indiana University School of Medicine, Indianapolis, Indiana, United States
- Schlader, Zachary, Indiana University, Bloomington, Indiana, United States
- Basile, David P., Indiana University School of Medicine, Indianapolis, Indiana, United States
Background
Heat-related kidney injury is an emerging cause of hospitalization and older adults are frequently admitted to hospital with kidney disorders during heat waves. Whether aging, per se, specifically predisposes to heat induced kidney injury is not well established. The purpose of this study was to compare the effects of a simulated heat wave on renal damage in young and old rats.
Methods
This study compared both young (3-5 months) and aged (16-20 months) male and female Wistar rats subjected a simulated heat wave. This was achieved by 4 consecutive days of exposure to ambient temperature of 36°C until core temperature (Tc) reached 40.5°C
or for a maximum of 3 hours. On day 5, rats were euthanized, and blood, kidney and urine samples collected.
Results
Wistar rats consistently reached TC of 40.5°C in less than 3 hours; on day 4, time to reach 40.5°C was similar in aged vs young Wistar rats (59±19 vs 57±11 min; NS). By comparison, Sprague-Dawley rats did not reach 40.5°C following up to 6 hours heat exposure. There was a significant increase in relative interstitial area in the kidneys of aged-heated male vs. non-heated controls (0.18 ± 0.02 vs 0.26 ± 0.05; p>0.05; N=6-8). Aged female rats, as well as young male and female rats, did not manifest increased interstitial inflammation following heat wave conditions. In some cases, kidneys of aged heated male rats contained apparent tertiary lymphoid structures. In addition, there were significant increases in mRNA expression of KIM-1 (~54%) and NGAL (~32%) in aged heated vs aged control rats. To gain insight into potential cellular pathways associated with heat induced kidney injury, single nuclear RNAseq was used to compare transcriptomic signatures of aged-heated vs control rats and identified several altered cell stress pathways, including those associated fatty acid metabolism and ER stress.
Conclusion
Wistar rats manifest impaired thermoregulation to acute heat stress, while aging male, but not female Wistar rats are predisposed to heat induced kidney injury associated with inflammation and evidence of tubular damage. The mechanisms leading to heat- induced injury require further investigation but may involve enhanced ER stress and altered cellular metabolism.
Funding
- NIDDK Support