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. On this basis, this article further discusses imbalance phenotype hypotheses, including microcirculation-dominant, mitochondria-dominant, and immunometabolism-dominant types, and proposes a multidimensional stratification approach corresponding to the pathological triangle model, focusing on renal microcirculation/tissue oxygenation assessment, mitochondrial-related biomarkers, and immunometabolic readouts. Additionally, potential time-windowed intervention pathways are outlined, ranging from preoperative risk optimization, intraoperative perfusion and oxygen delivery management, to postoperative mitochondrial protection and immunometabolic regulation. This article aims to provide a more integrated pathophysiological framework for the mechanistic classification, risk stratification, and multi-target intervention strategies for perioperative AKI.