Hemodynamic forces have an important role in venous intimal hyperplasia, which is the main cause of arteriovenous fistula dysfunction. Endothelial cells (ECs) constantly exposed to the shear stress of blood flow, converted the mechanical stimuli into intracellular signals, and interacted with the underlying vascular smooth muscle cells (VSMCs). Caveolin-1 is one of the important mechanoreceptors on cytomembrane, which is related to vascular abnormalities. Extracellular signal-regulated kinase1/2 (ERK1/2) pathway is involved in the process of VSMCs proliferation and migration. In the present study, we explore the effects of Caveolin-1-ERK1/2 pathway and uremia toxins on the endothelial cells and VSMCs following shear stress application. Different shear stress was simulated with a ECs/VSMCs cocultured parallel-plate flow chamber system. Low shear stress and oscillating shear stress up-regulated the expression of fibroblast growth factor-4, platelet-derived growth factor-BB, vascular endothelial growth factor-A, ERK1/2 phosphorylation in endothelial cells, and proliferation and migration of VSMCs but down-regulated the Caveolin-1 expression in endothelial cells. Uremia toxin induces the proliferation and migration of VSMCs but not in a Caveolin-1-dependent manner in the static environment. Low shear stress-induced proliferation and migration of VSMCs is inhibited by Caveolin-1 overexpression and ERK1/2 suppression. Shear stress-regulated VSMC proliferation and migration is an endothelial cells-dependent process. Low shear stress and oscillating shear stress exert atherosclerotic influences on endothelial cells and VSMCs. Low shear stress modulated proliferation and migration of VSMCs through Caveolin-1-ERK1/2 pathway, which suggested that Caveolin-1 and ERK1/2 can be used as a new therapeutic target for the treatment of arteriovenous fistula dysfunction.Impact statement: Venous intimal hyperplasia is the leading cause of arteriovenous fistula (AVF) dysfunction. This article reports that shear stress-regulated vascular smooth muscle cells (VSMCs) proliferation and migration is an endothelial cell (EC)-dependent process. Low shear stress (LSS) and oscillating shear stress (OSS) exert atherosclerotic influences on the ECs and VSMCs. LSS-induced proliferation and migration of VSMCs is inhibited by Caveolin-1 overexpression and extracellular signal-regulated kinase1/2 (ERK1/2) suppression, which suggested that Caveolin-1 and ERK1/2 can be used as a new therapeutic target for the treatment of AVF dysfunction.

Background: Acute kidney injury (AKI) occurs commonly in the intensive care unit (ICU). Insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinase-2 (TIMP-2), known as [TIMP-2] x [IGFBP7] (NephroCheck), have been identified as novel biomarkers for the prediction of AKI risk. However, the effective use of disease biomarkers is indispensable from an appropriate clinical context. We conducted a retrospective cohort study to find risk factors and assess the performance of the combination of NephroCheck with risk factors, so as to provide feasible information for AKI prediction.Methods: All patients who were admitted in the ICU (from June 2016 to July 2017) participated in the study. The primary outcome was the detection of severe AKI within the first 7 days after patients being admitted to the ICU. The predictors were separated into three categories: chronic risk factors, acute risk factors and biochemical indicators.Results: The study included 577 patients. 96 patients developed to severe AKI (16.6%) within 7 days. In addition to NephroCheck (+) (OR = 2.139, 95% CI (1.260–3.630),P = 0.005), age > 65 years (OR = 1.961, 95% CI (1.153–3.336),P = 0.013), CKD (OR = 2.573, 95% CI (1.319–5.018),P = 0.006) and PCT (+)(OR = 3.223, 95% CI (1.643–6.321),P = 0.001) were also the independent predictors of severe AKI within 7 days. Compared to NephroCheck (+) only (AUC = 0.66, 95% CI:0.60–0.72), the combination of NephroCheck (+) and risk factors (age > 65 years, CKD and PCT positive) (AUC = 0.75, 95% CI:0.70–0.81) led to a significant increase in the area under ROC curve for severe AKI prediction within 7 days.Conclusions: Although NephroCheck is an effective screening tool for recognizing high-risk patients, we found that combination with biomarker and risk factors (age > 65 years, CKD, procalcitonin positive) for risk assessment of AKI has the greatest significance to patients with uncertain disease trajectories.

Background: Acute kidney injury (AKI) occurs commonly in the intensive care unit (ICU). Insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinase-2 (TIMP-2), known as [TIMP-2] x [IGFBP7] (NephroCheck), have been identified as novel biomarkers for the prediction of AKI risk. However, the effective use of disease biomarkers is indispensable from an appropriate clinical context. We conducted a retrospective cohort study to find risk factors and assess the performance of the combination of NephroCheck with risk factors, so as to provide feasible information for AKI prediction.Methods: All patients who were admitted in the ICU ( from June 2016 to July 2017) participated in the study. The primary outcome was the detection of severe AKI within the first seven days after patients being admitted to the ICU. The predictors were separated into three categories: chronic risk factors, acute risk factors and biochemical indicators. Results: The study included 577 patients. 96 patients developed to severe AKI (16.6%) within seven days. In addition to NephroCheck (+) (OR=2.139, 95% CI (1.260-3.630), P =0.005), age >65 years (OR=1.961, 95% CI (1.153-3.336), P=0.013), CKD (OR=2.573, 95% CI (1.319-5.018), P=0.006) and PCT (+)(OR=3.223, 95% CI (1.643-6.321), P=0.001) were also the independent predictors of severe AKI within seven days. Compared to NephroCheck (+) only (AUC=0.66, 95% CI:0.60-0.72), the combination of NephroCheck (+) and risk factors (age>65years, CKD and PCT positive) (AUC=0.75, 95% CI:0.70-0.81) led to a significant increase in the area under ROC curve for severe AKI prediction within seven days.Conclusions: Although NephroCheck is an effective screening tool for recognizing high-risk patients, we found that combination with biomarker and risk factors (age>65years, CKD, procalcitonin positive) for risk assessment of AKI has the greatest significance to patients with uncertain disease trajectories.