A model of recurrent heat stress that causes kidney disease in mice.

Authors

Hung Nguyen, Anna D Montgomery, Cassidy Rehage, Nicholas Harris, Bryan K Becker, Malgorzata Kasztan, Paul W Sanders, Roxana C Chicas, Subhashini Bolisetty, Kelly A Hyndman

Published in

American journal of physiology. Renal physiology. Sep 14, 2026. Epub Sep 14, 2026.

Abstract

Chronic kidney disease of non-traditional origin disproportionately affects outdoor workers exposed to high environmental temperatures. Recurrent heat stress with dehydration (rHS) is a major contributor to kidney injury; however, the underlying mechanisms remain poorly understood. We aimed to develop and validate a reproducible murine model of rHS-induced chronic kidney disease (CKD) in male and female mice. Young C57BL/6J mice were assigned to ambient temperature controls (AT), a single heat stress exposure (HS1), or recurrent heat stress (rHS; nine exposures over three weeks). Each exposure consisted of 3 h at 40°C and 50% relative humidity without access to food or water, resulting in dehydration with an acute 4-6.5% reduction in body mass. One month after protocol initiation, male rHS mice exhibited a significant decline in glomerular filtration rate (ΔGFR = -56.5±87 μL/min), elevated plasma creatinine (0.07±0.01 vs. 0.11±0.02 mg/dL, P< 0.001), and increased albuminuria (65±21 vs. 198±92 μg/mg creatinine, P<0.001). Female rHS mice also exhibited increased plasma creatinine (0.08±0.004 vs. 0.11±0.02 mg/dL, P=0.002) but demonstrated a smaller decline in GFR and minimal albuminuria. Histological analysis revealed tubular injury, interstitial fibrosis, and glomerulosclerosis in both sexes. Compared with AT controls, renal PECAM1-positive area was reduced by 42.5% in males and 31.6% in females, indicating microvascular loss, and was accompanied by increased renal macrophage and T-cell accumulation. These findings establish a murine model of kidney injury induced by recurrent heat stress-mediated dehydration in both sexes, although young female mice exhibited partial protection from adverse renal effects.

PMID:
42734479
Bibliographic data and abstract were imported from PubMed on 14 Sep 2026.

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