Acute heat stress upregulates Akr1b3 through Nrf-2 to increase endogenous fructose leading to kidney injury.

In recent years, the prevalence of extremely high-temperature climates has led to an increase in cases of acute heat stress (HS), which has been identified as a contributing factor to various kidney diseases. Fructose, the end product of the polyol pathway, has been linked to kidney conditions such as kidney stones, chronic kidney disease, and acute kidney injury. However, the relationship between acute HS and kidney injury caused by endogenous fructose remains unclear. The study found that acute HS triggers the production of reactive oxygen species, which in turn activate the Nrf-2 and Akr1b3 leading to an increase in endogenous fructose levels in kidney cells. It was further demonstrated that the elevated levels of endogenous fructose play a crucial role in causing damage to kidney cells. Moreover, inhibiting Nrf-2 effectively mitigated kidney damage induced by acute HS by reducing endogenous fructose levels. These findings underscore the detrimental impact of excessive fructose resulting from acute stress on kidney function, offering a novel perspective for future research on the prevention and treatment of acute HS-induced kidney injury.