Predictive value of serum ß2-microglobulin in cardiac valve calcification in maintenance hemodialysis patients.

Background: Cardiac valve calcification (CVC) is associated with adverse cardiovascular events. We studied the risk factors of CVC in maintenance hemodialysis (MHD) patients and the value of serum ß2-microglobulin (ß2-MG) levels in predicting the incidence of CVC. ß2-MG is a middle molecular weight toxin. In recent years, researchers found that elevated blood ß2-MG was associated with coronary, thoracic, and abdominal aortic calcifications with significant correlations. ß2-MG has been emerging as a strong biomarker for cardiovascular mortality in uremic patients but its role in CVC is not well studied. This study looked specifically at CVC occurrence in relation to ß2-MG for MHD patients. Methods: Patients who underwent MHD for more than 3 months in the First People's Hospital of Nantong City from November 2012 to November 2019 with complete available data were included in the study. The patients were divided into the CVC group and the non-CVC group. The general information and clinical laboratory indicators of the patients were collected in a retrospective manner. We analyzed the risk factors for developing CVC in MHD patients using binary logistic regression method. Receiver operating characteristic (ROC) curves were used to calculate the cut-off value of ß2-MG for predicting CVC. The decision tree (DT) method was used to classify and explore the probability of CVC in patients with MHD. Results: The ß2-MG in the CVC group was significantly higher than that in the non-CVC group (t=6.750, P<0.001). Multivariate binary logistic regression analysis showed that gender, age, serum ß2-MG, and hemodialysis (HD) adequacy (Kt/V urea) were independent risk factors for CVC in MHD patients. ROC analysis showed that a ß2-MG value of 25 µg/L was the best cut-off point for predicting CVC in MHD patients. According to binary logistic regression analysis, the ß2-MG ≥25 µg/L group was 3.39 times more likely to develop CVC than the ß2-MG <25 µg/L group [odds ratio (OR), 3.39; 95% confidence interval (CI), 1.63-7.06; P=0.001]. The DT model determined that serum ß2-MG ≥25 µg/L and age >69 years were important determinants for predicting CVC in MHD patients. Conclusions: Serum ß2-MG in MHD patients has a positive correlation with the severity and occurrence of CVC.

Lower Hydrogen Sulfide Is Associated with Cardiovascular Mortality, Which Involves cPKCßII/Akt Pathway in Chronic Hemodialysis Patients.

BACKGROUND/AIMS: To evaluate the relationship between plasma hydrogen sulfide (H2S) and cardiovascular risk markers, including pulse pressure (PP), left ventricular mass index (LVMI) and intima-media thickness (IMT), and mortality in chronic hemodialysis (CHD) patients and further investigate the underlying cardiovascular protection mechanism of H2S. METHODS: CHD patients, 113 of them, were studied. Plasma H2S was measured through zinc acetate reaction. cPKCßII membrane translocation and phosphorylation of Akt were detected by western blot. RESULTS: Lower plasma H2S level in CHD patients was predictor of an increased PP, LVMI and IMT. Patients with lower H2S had a lower survival at the end of the study. H2S was an independent predictor of all-cause and cardiovascular mortality when adjusted for other risk factors. CHD patients with lower H2S showed an increase of cPKCßII activation, but phosphorylation of Akt decreased. The level of VCAM-1 and ICAM-1 increased significantly. CONCLUSIONS: Lower plasma H2S in CHD patients is associated with cardiovascular risk factors and mortality, which may be mediated by the cPKCßII/Akt pathway and further VCAM-1/ICAM-1 upregulation.

Serum hepcidin predicts uremic accelerated atherosclerosis in chronic hemodialysis patients with diabetic nephropathy.

BACKGROUND: Hepcidin, as a regulator of body iron stores, has been recently discovered to play a critical role in the pathogenesis of anemia of chronic disease. Atherosclerotic cardiovascular disease is the most common complication and the leading cause of death in chronic hemodialysis (CHD) patients. In the current study, we aimed to explore the relationship between serum hepcidin and uremic accelerated atherosclerosis (UAAS) in CHD patients with diabetic nephropathy (CHD/DN). METHODS: A total of 78 CHD/DN and 86 chronic hemodialyzed nondiabetic patients with chronic glomerulonephritis (CHD/non-DN) were recruited in this study. The level of serum hepcidin-25 was specifically measured by liquid chromatography-tandem mass spectrometry. Serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay. RESULTS: High serum level of hepcidin-25 was seen in CHD patients. Serum hepcidin-25 in CHD/DN was significantly higher than that in CHD/non-DN patients. Serum hepcidin-25 was positively correlated with ferritin, high-sensitivity C-reactive protein (hs-CRP), TNF-α, and IL-6 in CHD/DN patients. CHD/DN patients exhibited higher common carotid artery intima media thickness (CCA-IMT), hs-CRP, and hepcidin-25 levels than that in CHD/non-DN patients. Moreover, in CHD/DN patients, CCA-IMT was positively correlated with serum hepcidin, hs-CRP, and low-density lipoprotein-cholesterol. On multiple regression analysis, serum hepcidin and hs-CRP level exhibited independent association with IMT in CHD/DN patients. CONCLUSIONS: These findings suggest possible linkage between iron metabolism and hepcidin modulation abnormalities that may contribute to the development of UAAS in CHD/DN patients.

Correlation of Lower Concentrations of Hydrogen Sulfide with Activation of Protein Kinase CßII in Uremic Accelerated Atherosclerosis Patients.

BACKGROUND: Hydrogen sulfide (H 2 S) plays a protective role in chronic hemodialysis (CHD) patients. In this study, we further investigate the relationship between H 2 S and conventional protein kinase CßII (cPKCßII) in CHD patients with uremic accelerated atherosclerosis (UAAS). METHODS: A total of 30 healthy people, 30 CHD patients without AS and 30 CHD patients with AS (CHD + AS) were studied. Plasma H 2 S was measured with a sulfide sensitive electrode, and cPKCßII membrane translocation was detected by Western blotting. RESULTS: Plasma H 2 S in CHD + AS group was significantly lower than that in CHD patients. cPKCßII membrane translocation in CHD + AS group increased significantly compared with CHD group. Plasma H 2 S concentration was negatively correlated with cPKCßII membrane translocation in CHD + AS patients. CONCLUSIONS: These findings suggest a possible linkage between H 2 S metabolism and cPKCßII activation, which may contribute to the development of UAAS in CHD patients.

Correlation of lower concentrations of hydrogen sulfide with atherosclerosis in chronic hemodialysis patients with diabetic nephropathy.

BACKGROUND/AIMS: To explore the relationship between hydrogen sulfide (H2S) and uremic accelerated atherosclerosis (UAAS) in chronic hemodialysis patients with diabetic nephropathy (CHD/DN). METHODS: A total of 36 CHD/DN and 32 chronic hemodialyzed non-diabetic patients with chronic glomerulonephritis (CHD/non-DN) were studied. Plasma H2S was measured with a sulfide sensitive electrode. RESULTS: Plasma H2S in CHD/DN was significantly lower than that in CHD/non-DN patients. Plasma H2S was positively correlated with plasma TGF-ß1, and negatively correlated with MMP-12 in CHD/DN patients. CHD/DN patients exhibited higher CCA-IMT, hsCRP, and lower H2S levels than in CHD/non-DN patients. Moreover, in CHD/DN patients, CCA-IMT was negatively correlated with plasma H2S, and positively correlated with hsCRP and LDL. On multiple regression analysis, H2S levels exhibited independent association with IMT in CHD/DN patients. CONCLUSIONS: These findings suggest possible linkage between H2S metabolism and TGF-ß/Smad signaling pathway modulation abnormalities that may contribute to the development of UAAS in CHD/DN patients.