The gut–kidney axis in high-altitude hypoxia: pathophysiological mechanisms and the central role of hypoxia inducible factor

作者：Pei Wu, Xun Li, Wenjie Long, Yu Ma, Bo Xue, Wen Xie, Xin Ma · 发表于：Annals of Medicine · 年份：2025 · DOI：10.1080/07853890.2025.2557514 · 被引用次数：7 · 研究领域：High Altitude and Hypoxia、Gut microbiota and health、Heme Oxygenase-1 and Carbon Monoxide

BACKGROUND: The high-altitude plateau environment, defined by hypobaric hypoxia, poses considerable health risks to human populations. Due to their substantial oxygen requirements, the kidneys are particularly susceptible, as are the intestines, with their intricate microbiota and essential barrier functions. This review examines the pathophysiological consequences of high-altitude hypoxia on renal and intestinal health, specifically highlighting the interorgan communication mediated by the gut-kidney axis. DISCUSSION: Prolonged hypobaric hypoxia causes notable functional and structural impairment in the kidneys, exacerbating pathologies such as acute kidney injury and chronic kidney disease, and is associated with altitude-induced disorders including polycythemia and hyperuricemia. Simultaneously, the hypoxic milieu disrupts gut microbiota composition, weakens intestinal barrier integrity and alters mucosal immune responses. These intestinal disturbances are increasingly acknowledged as pivotal factors in renal pathophysiology via the gut-kidney axis. Microbial metabolites and compromised barrier function may enter systemic circulation, triggering inflammation and fibrotic processes. The hypoxia-inducible factor pathway emerges as a central molecular mechanism activated in both organs, modulating critical processes such as renal fibrosis and intestinal permeability. Furthermore, dietary habits common among high-altitude populations can influence gut microbiota, introducing a...