Exertional heat stroke-related acute kidney injury: novel animal and cellular models

Exertional heat stroke (EHS) is a life-threatening condition frequently complicated by acute kidney injury (AKI), yet standardized experimental models remain limited. This study aimed to establish reproducible in vivo and in vitro models specifically for EHS-induced AKI (EHS-AKI). Male C57BL/6J mice underwent exercise in a heat stress environment. We evaluated the effects of dehydration before heat exposure (12 h without water) and different relative humidity levels (55%, 65%, 75%) on renal outcomes. The results showed that compared with the free drinking water control group, water deprivation significantly exacerbated renal dysfunction (manifested as increased serum creatinine and urea nitrogen levels) and aggravated renal pathological changes. Research has determined that an environmental condition of 39.5 °C combined with 65% relative humidity is the optimal condition for inducing severe but non lethal AKI. In addition, we constructed an in vitro model using HK2 cells exposed to high temperature (42.7 °C). Research has found that when the concentration ratio of myoglobin to L-ascorbic acid (Mb: Vit C) is 1:2, it can induce the maximum upregulation of the renal injury marker neutrophil gelatinase-associated lipocalin and lead to a significant decrease in cell viability, thus simulating thermal injury related to rhabdomyolysis. In summary, this study validated a dehydrated mouse model and optimized cell experiment protocol, providing an important tool for exploring the pathophysiological mechanisms and potential therapies of exertional heat stroke associated acute kidney injury.