Role of the endothelial cell glycocalyx in sepsis-induced acute kidney injury

Abstract

Sepsis-induced acute kidney injury (S-AKI) is a common complication of sepsis. It occurs at high incidence and is associated with a high level of mortality in the intensive care unit (ICU). The pathophysiologic mechanisms underlying S-AKI are complex, and include renal vascular endothelial cell dysfunction. The endothelial glycocalyx (EG) is a polysaccharide/protein complex located on the cell membrane at the luminal surface of vascular endothelial cells that has anti-inflammatory, anti-thrombotic, and endothelial protective effects. Recent studies have shown that glycocalyx damage plays a causal role in S-AKI progression. In this review, we first describe the structure, location, and basic function of the EG. Second, we analyze the underlying mechanisms of EG degradation in sepsis and S-AKI. Finally, we provide a summary of the potential therapeutic strategies that target the EG.

Keywords: endothelium; glycocalyx; inflammation; kidney; sepsis.

Figure 1

S-AKI is associated with a complex array of mechanisms. The pathophysiologic mechanisms included acute tubular necrosis, oxidative stress, inflammatory responses, mitochondrial dysfunction, microvascular dysfunction, and ischemic. Sepsis-related injury factors cause the degradation of the glycocalyx, which leads to vascular endothelial dysfunction and is an important mechanism causing acute tubular necrosis during S-AKI. S-AKI, Sepsis-induced acute kidney injury.

Figure 2

(a) Normal glycocalyx structure. (b) Mechanisms of sepsis-induced glycocalyx damage: shear stress, lysosome-related organelles, inflammatory response, oxidative stress, and some metallohydrolases. MMPs, matrix metalloproteinases; ADAMs, A Disintegrin And Metalloproteinase Domain-containing Proteins; IL-1β, Interleukin-1β; IL-6, Interleukin-6; IL-10, Interleukin-10; TNF-α, Tumor Necrosis Factor-α; CD44, Cluster of Differentiation 44; vWF, Von Willebrand Factor; SOD, Reactive Oxygen Species; ICAM-1, Intercellular Adhesion Molecule-1; VCAM-1, Vascular Cell Adhesion Molecule-1.

Figure 3

Potential therapeutic approaches and targets for sepsis-induced acute kidney injury, including reducing the production of inflammatory factors, weakening the activity of metallohydrolases, SIRT1-related treatments, inhibiting the shedding of glycocalyx components, and repairing the glycocalyx. VC, Vitamin C; IFN-β, Interferon-β; SIRT-1, Sirtuin 1; MMPs, matrix metalloproteinases; ADAMs, A Disintegrin And Metalloproteinase Domain-containing Proteins; IL-1β, Interleukin-1β; IL-6, Interleukin-6; IL-10, Interleukin-10; TNF-α, Tumor Necrosis Factor-α; FGF, Fibroblast Growth Factor; LNPG, liposomal nanocarriers of pre-assembled glycocalyx; SIRT1, Sirtuin 1; SDX, sulodexide; ROS, Reactive Oxygen Species.