Figure 1.

Clinical course and pathophysiology of SA-AKI. Sepsis is the most common cause of AKI in critically ill patients. However, sepsis and AKI predispose hosts to each other, and it is often difficult to determine the exact timing of the onset of these two syndromes clinically. There is increasing evidence that the pathogenesis of SA-AKI is the “unified theory” theory involving the interaction between inflammation, microcirculation dysfunction, and metabolic reprogramming. The pathophysiology of SA-AKI involves injury and dysfunction of many cell types, including macrophages, ECs, and RTECs. PAMP and/or DAMP released from damaged tissues activate and promote the pro-inflammatory phenotype (M1) of macrophages, resulting in the release of pro-inflammatory cytokines and chemokines, which can cause damage to kidney tissues. The second cell type that is vulnerable is the EC. Sepsis stimulates endothelial cells to produce nitric oxide, which causes blood vessels to dilate. Many molecules simultaneously control microvascular permeability, resulting in insufficient blood volume relative to the vessel when tight cellular connections loosen. In addition, during the period of sepsis, confirmed microvascular thrombosis related to inflammation. In RTECs, infiltration of inflammatory cells and a large number of inflammatory factors lead to deterioration of renal function, apoptotic cell death, and sublethal injury.