Pathological triad of perioperative acute kidney injury: renal microcirculatory hypoxia, mitochondrial damage, and immuno-metabolic reprogramming

Perioperative acute kidney injury (AKI) is one of the common and burdensome complications following surgical procedures. The traditional “prerenal” model centered on systemic hemodynamic disturbances fails to adequately account for occult hypoxia that can occur despite relatively stable macro-parameters, as well as significant clinical heterogeneity.

Recent clinical and translational studies suggest that perioperative AKI is better characterized as a syndrome involving imbalances in local microcirculation, cellular energy metabolism, and the immune-inflammatory network. Although perioperative AKI is not a typical autoinflammatory disease, the sterile inflammation driven by DAMPs shares common mechanistic features with autoinflammatory syndromes, such as NLRP3 inflammasome activation and its mediated inflammatory amplification.

Based on this, this article proposes a “renal microcirculatory hypoxia–mitochondrial injury–immunometabolic reprogramming” pathological triangle model as a conceptual framework for understanding the occurrence, development, and heterogeneity of perioperative AKI. This model emphasizes the shifting dominance of these three components across distinct time windows, as well as their coupled nature and mutually amplifying positive feedback loops.