Microparticles from Hyperphosphatemia-Stimulated Endothelial Cells Promote Vascular Calcification Through Astrocyte-Elevated Gene-1.

Endothelial microparticles (EMPs) can be released in chronic kidney disease (CKD). Plasma concentration of high inorganic phosphate (HP) is considered as a decisive determinant of vascular calcification in CKD. We therefore explored the role of HP-induced EMPs (HP-EMPs) in the vascular calcification and its potential mechanism. We observed the shape of HP-EMPs captured by vascular smooth muscle cells (VSMCs) dynamically changed from rare dots, rosettes, to semicircle or circle. Our results demonstrated that HP-EMPs could directly promote VSMC calcification, or accelerate HP-induced calcification through signal transducers and activators of transcription 3 (STAT3)/bone morphogenetic protein-2 (BMP2) signaling pathway. AEG-1 activity was increased through HP-EMPs-induced VSMC calcification, in arteries from uremic rats, or from uremic rats treated with HP-EMPs. AEG-1 deficiency blocked, whereas AEG-1 overexpression exacerbated, the calcium deposition of VSMCs. AEG-1, a target of miR-153-3p, could be suppressed by agomiR-153-3p. Notably, VSMC-specific enhance of miR-153-3p by tail vein injection of aptamer-agomiR-153-3p decreased calcium deposition in both uremia rats treated with HP-EMPs or not. HP-EMPs could directly induce VSMCs calcification and accelerate Pi-induced calcification, and AEG-1 may act as crucial regulator of HP-EMPs-induced vascular calcification. This study sheds light on the therapeutic agents that influence HP-EMPs production or AEG-1 activity, which may be of benefit to treat vascular calcification.

Causes and predictors of mortality from lupus nephritis in Southern Hunan, China.

OBJECTIVES: The objective of the study was to explore the causes and predictors of mortality in a cohort of LN with LN in southern Hunan, China. METHODS: We analyzed 236 patients with biopsy-proven LN during 2010-2018. Demographic data, laboratory data, SLEDAI scores, treatment strategies, and comorbidity were collected. Cox regression analysis was carried out to determine the independent predictors of mortality. RESULTS: The patients had mean disease duration of 67.9 ± 28.2 months. Class IV LN was the predominant biopsy class within the cohort (38.1%). After 1 year therapy, the majority of patients achieved complete remission (72.9%) and 44 (18.6%) patients achieved partial remission. The 5- and 10-years survival rates for our cohort were 94.4 and 85.2%, respectively. There were 18 deaths (7.6%), of which the main causes were infection (50%) alone and cardiovascular diseases (27.8%). Independent predictors of mortality in our cohort were: platelet-to-neutrophil ratio (PNR) [hazard ratio (HR) 5.910; confidence interval (CI) 1.253-27.875], onset age (HR 1.090; CI 1.035-1.147), and SLEDAI scores (HR 1.258; CI 1.068-1.482). CONCLUSION: We firstly revealed that PNR might be a promising predictor of mortality and reported the causes and prognostic predictors of mortality in LN from southern Hunan, China.

Predictive value of the neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-neutrophil ratio, and neutrophil-to-monocyte ratio in lupus nephritis.

OBJECTIVE: To evaluate the role of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-neutrophil ratio (PNR), platelet-to-monocyte ratio (PMR), and neutrophil-to-monocyte ratio (NMR) as predictors for lupus nephritis (LN) patients without infection or as biomarkers for distinguishing between infection or flare with LN patients. METHODS: LN patients were divided into three groups: LN without infection, LN with infection, and LN with flare. A total of 57 healthy subjects were enrolled as controls. The differentiation was analyzed between LN without infection and control group, and LN with infection and LN with flare. Correlations among variables were assessed in the LN group without infection. Receiver operating characteristic curves were constructed in two comparable groups. RESULTS: NLR, PLR, and MLR were increased significantly in the LN group without infection as compared with those in healthy controls. NLR (area under the curve (AUC): 0.75) and MLR (AUC: 0.79) were useful for distinguishing between LN patients without infection and healthy subjects. In differentiating LN patients without infection from the controls, optimal cutoffs of NLR and MLR were 3.43 (sensitivity: 45.6%, specificity: 96.5%, and overall accuracy: 68.8%) and 0.24 (sensitivity: 75.0%, specificity: 73.7%, and overall accuracy: 73.6%), respectively. In addition, NLR (r = 0.322, p = 0.011) and PLR (r = 0.283, p = 0.026) were positively correlated with CRP. Importantly, NLR and NMR were increased while PNR was decreased in the LN group with infection in comparison with those in the LN group with flare. NLR (AUC: 0.80), NMR (AUC: 0.78), and PNR (AUC: 0.74) were useful in differentiating LN patients with infection and flare, and their optimal cutoffs were 4.02 (sensitivity: 82.6%, specificity: 69.6%, and overall accuracy: 75.5%), 12.19 (sensitivity: 80.4%, specificity: 73.9%, and overall accuracy: 77.5%), and 28.26 (sensitivity: 65.2%, specificity: 76.8%, and overall accuracy: 71.6%), respectively. CONCLUSIONS: We demonstrated, for the first time, that MLR or NMR had the best accuracy in differentiating LN patients without infection from healthy subjects, or differentiating infection from flare in LN patients, respectively. Our results implied that NLR, MLR, PNR, and NMR may be useful biomarkers in predicting LN.