No abstract

Monocyte/HDL cholesterol ratio was increased with decreasing eGFR in predialytic CKD patients. Most importantly, we report for the first time that an increased M/H ratio was cross-sectionally associated with a worse cardiovascular profile and arose as independent predictors of major cardiovascular events during follow-up.

Plasma endocan levels are elevated in a large number of diseases, and may reflect endothelial cell dysfunction. There are currently no data on endocan in patients with chronic kidney disease (CKD). Therefore, we measured plasma endocan in 251 patients with CKD (stage 1-5) and 60 control individuals. Plasma endocan concentrations correlated with estimated glomerular filtration rate (eGFR), different markers of inflammation (pentraxin 3 and high-sensitivity C-reactive protein), and vascular abnormalities (flow-mediated vasodilation (FMV) and carotid intima media thickness (CIMT)). All-cause mortality and cardiovascular events (CVE) were also analyzed with respect to plasma endocan. Patients with CKD showed significantly increased plasma endocan (4.7 [IQR 1.9-9.4] compared with controls [IQR 1.1-1.5] ng/ml), with values progressively higher across stages of CKD. On univariate analysis, plasma endocan concentrations correlated negatively with eGFR and FMV, but positively with both markers of inflammation and CIMT. However, on multivariate analysis only high-sensitivity C-reactive protein, FMV, and CIMT remained significantly associated with plasma endocan. On Cox survival analysis, endocan levels were associated with all-cause mortality and CVE in these patients. Thus, plasma endocan increases in the presence of decreasing eGFR and influences all-cause mortality and CVE in patients with CKD independent of traditional and nontraditional risk factors.

Studies in animals show that fibroblast growth factor (FGF)-23 interferes with vascular reactivity induced by the nitric oxide (NO) system. To investigate the relationship between circulating FGF-23 levels and the response of forearm blood flow to ischemia (flow-mediated vasodilatation, FMD) and nitroglycerin, we tested 183 patients with stage 3-4 chronic kidney disease (CKD). None of them had cardiovascular complications or were taking drugs interfering with vascular function. Patients with FGF-23 levels above the median had significantly lower glomerular filtration rate, FMD, and fetuin-A levels (an anti-inflammatory molecule and potent inhibitor of calcification). They also had higher proteinuria and phosphate levels when compared to patients whose FGF-23 levels were below the median. The response to nitroglycerin was not different between the two groups. Multiple regression analysis showed that the relationship between FGF-23 and FMD was only modestly sensitive to adjustment for classical risk factors, biomarkers of bone mineral metabolism, high-sensitivity C-reactive protein, and homeostatic model assessment index. Adjustment for asymmetrical dimethyl arginine (ADMA) weakened the strength of this link; however, it remained highly significant. There was no independent association between FGF-23 and nitroglycerin. Thus, attenuation of FMD by ADMA suggests that this endogenous inhibitor of NO synthase may, in part, mediate the vascular effects of FGF-23 in patients with CKD.