ABSTRACT
Carotid-femoral pulse wave velocity (Cf-PWV) can well predict the prognosis of the general population. However, whether Cf-PWV can be used as a prognostic indicator in maintenance hemodialysis (MHD) patients remains mysterious. The present study endeavored to explore the prognostic value of Cf-PWV among the MHD population. Patients who received MHD and underwent Cf-PWV examination at the hemodialysis center of Zhejiang Provincial People's Hospital between March 1, 2017 and October 15, 2019 were enrolled. Relevant clinical data were collected from these patients, who were subsequently followed up for a minimum of 1 year. During the follow-up period, the occurrence of all-cause death was recorded as a prognostic indicator. Based on the predetermined inclusion and exclusion criteria 178 patients were included in the final analysis. These patients were categorized into 2 groups based on Cf-PWV values: group 1 (Cf-PWVâ <â 13.8 m/s), and group 2 (Cf-PWVâ ≥â 13.8 m/s). Thirty-four patients succumbed to their conditions within a median follow-up period of 23.3 months. Kaplan-Meier survival analysis revealed that the median survival time of group 2 was significantly shorter than group 1 (log-rank test, χ2â =â 12.413, Pâ <â .001). After adjusting for various factors, including age, cardiovascular disease, peripheral arterial diastolic pressure, central arterial diastolic pressure, albumin, blood urea nitrogen, serum creatinine, left ventricular ejection fraction, 25 hydroxyvitamin D3, C-reactive protein and serum phosphorus, it was found that Cf-PWVâ ≥â 13.8m/s was an independent risk factor for all-cause mortality in MHD patients (relative riskâ =â 3.04, 95% confidence interval [CI]â =â 1.22-7.57; Pâ =â .017). A high level of Cf-PWV (≥13.8 m/s) is an independent risk factor for all-cause death in MHD patients.
Subject(s)
Carotid-Femoral Pulse Wave Velocity , Renal Dialysis , Humans , Female , Male , Middle Aged , Prognosis , Aged , Kaplan-Meier Estimate , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/physiopathology , Kidney Failure, Chronic/mortality , Risk Factors , Pulse Wave Analysis , AdultABSTRACT
The sepsis-associated acute kidney injury (Sa-AKI) is closely related to high mortality rates worldwide. Injury to the renal proximal tubular epithelial cells (RPTECs), caused by pathological conditions, is a major cause of acute kidney injury (AKI). The lncRNA NORAD has been reported to be positively associated with kidney cancers. However, the biological roles and underlying mechanisms of NORAD in RPTECs during AKI are still unclear. In this study, we found that NORAD was significantly downregulated in RPTECs from AKI tissues. Overexpression of NORAD alleviated RPTECs injury induced by lipopolysaccharide (LPS). Additionally, glucose metabolism was significantly impaired during AKI, and LPS treatment inhibited glucose metabolism in RPTECs. We demonstrated that NORAD rescued the LPS-induced inhibition of glucose metabolism in RPTECs. Furthermore, miRNA-155-5p was significantly upregulated in RPTECs from AKI. Through bioinformatics analysis, RNA pull-down, RNA IP, and luciferase assays, we showed that NORAD directly associated with miR-155-5p to downregulate its expression. Moreover, overexpression of miR-155-5p inhibited glucose metabolism by directly targeting the 3'UTR of the glucose metabolism enzyme, pyruvate dehydrogenase kinase 1 (PDK1). Finally, rescue experiments validated that NORAD's protective effect on RPTECs injury was mediated through modulation of the miR-155-5p-PDK1-glucose metabolism pathway. In summary, these results reveal that lncRNA NORAD can alleviate RPTECs dysfunction by targeting the miR-155-5p-PDK1 axis, suggesting that NORAD has the potential to contribute to the development of therapeutic approaches against Sa-AKI.