The Programmed Cell Death of Macrophages, Endothelial Cells, and Tubular Epithelial Cells in Sepsis-AKI

Abstract

Sepsis is a systemic inflammatory response syndrome caused by infection, following with acute injury to multiple organs. Sepsis-induced acute kidney injury (AKI) is currently recognized as one of the most severe complications related to sepsis. The pathophysiology of sepsis-AKI involves multiple cell types, including macrophages, vascular endothelial cells (ECs) and renal tubular epithelial cells (TECs), etc. More significantly, programmed cell death including apoptosis, necroptosis and pyroptosis could be triggered by sepsis in these types of cells, which enhances AKI progress. Moreover, the cross-talk and connections between these cells and cell death are critical for better understanding the pathophysiological basis of sepsis-AKI. Mitochondria dysfunction and oxidative stress are traditionally considered as the leading triggers of programmed cell death. Recent findings also highlight that autophagy, mitochondria quality control and epigenetic modification, which interact with programmed cell death, participate in the damage process in sepsis-AKI. The insightful understanding of the programmed cell death in sepsis-AKI could facilitate the development of effective treatment, as well as preventive methods.

Ginsenoside Rg1 ameliorates sepsis-induced acute kidney injury by inhibiting ferroptosis in renal tubular epithelial cells

“…Ginsenoside Rg1 can reduce ROS generation and aldosterone‐elicited autophagy in MPC5 mouse podocyte cells and NRK‐52E rat renal tubular cells 35,36 . As the fundamental elements of the kidney, renal tubules, and glomeruli, mainly comprising glomerular mesangial cells, TECs, and ECs, are responsible for kidney function; moreover, damaged kidney tubules are distinctly observed in sepsis animal models and patients 11 . Hence, to validate the role of ginsenoside Rg1 in ferroptosis in vitro, we treated HK‐2 cells with LPS and then we found consistent results in cell experiments.…”

“…The current paradigm of interpretation of SI‐AKI appears to shift progressively from vasoconstriction and hypoperfusion to vasodilation and hyperemia, and from acute renal tubular necrosis to renal tubular cell apoptosis, dysfunction, or detachment 8–10 . More importantly, programmed cell death of renal tubular epithelial cells (TECs), such as apoptosis, pyroptosis, and necroptosis could be stimulated by sepsis, which facilitates AKI progress 11 . However, the known patterns of kidney cell death cannot completely elucidate the changes in SI‐AKI.…”

“…[8][9][10] More importantly, programmed cell death of renal tubular epithelial cells (TECs), such as apoptosis, pyroptosis, and necroptosis could be stimulated by sepsis, which facilitates AKI progress. 11 However, the known patterns of kidney cell death cannot completely elucidate the changes in SI-AKI. Consequently, it is paramount and urgent to unravel the mechanism of SI-AKI and seek novel and effective strategies for treating SI-AKI.…”

Clinical Value of Prognostic Nutritional Index and Neutrophil-to-Lymphocyte Ratio in Prediction of the Development of Sepsis-Induced Kidney Injury

“…Acute kidney injury, defined as a rapid decrease in glomerular filtration rate that results in raised serum creatinine levels, imposes a serious disease burden on hospitalized patients. Sepsis is the leading cause of AKI, especially in individuals with severe sepsis [ 2 , 22 ]. Early sepsis is characterized by an organism's proinflammatory response mediated by neutrophils, macrophages, and other immune cells, referred to as the hyperdynamic phase.…”

Multi-Omics Techniques Make it Possible to Analyze Sepsis-Associated Acute Kidney Injury Comprehensively

“…Since SA-AKI can occur in the absence of clinical symptoms of renal hypoperfusion and hemodynamic instability and the presence of normal or increased global renal blood flow, it is gradually recognized that ischemia-reperfusion injury is not the only mechanism of SA-AKI, and the “unified theory” theory is widely accepted ( Figure 1 ). The pathophysiology of SA-AKI involves injury and dysfunction of many cell types, including macrophages, vascular endothelial cells (ECs), and renal tubular epithelial cells (TECs), as well as their crosstalk and association ( 30 ). There is increasing evidence that the pathogenesis of SA-AKI is multifactorial and complex, involving the interaction between inflammation, microcirculation dysfunction, and metabolic reprogramming.…”