Effect of unfractionated heparin, enoxaparin and sulodexide on the relations between secretion and expression of OPG, RANKL and vWF in HUVEC

Heparin modulates function of vascular endothelium. We studied the effects of unfractionated heparin (UFH) vs. enoxaparin vs. sulodexide on the levels and gene expression of osteoprotegerin (OPG), Receptor Activator of Nuclear Factor kB Ligand (RANKL) and von Willebrand factor (vWF) in Human Umbilical Vein Endothelial Cells (HUVEC) culture. HUVEC were isolated from human umbilical vein by a standard method. The supernatant concentrations (ELISA) and gene expression (Real Time-PCR) of OPG, RANKL and vWF in HUVEC were determined after incubation with various concentrations of UFH, enoxaparin and sulodexide for up to 16 hours. In control HUVEC strong positive correlation between OPG and vWF levels was observed, whereas sRANKL negatively correlated with OPG and vWF levels. Only in control HUVEC a negative correlation between the supernatant level of vWF and its gene expression was found. Already the lowest concentration of UFH caused 2.5-fold increase in OPG gene expression while higher UFH concentrations substantially increased RANKL mRNA level. A negative correlation between the OPG and sRANKL concentration was noticed in supernatant HUVEC which were incubated with enoxaparine. In conclusion, the observed interrelationships between OPG, RANKL and vWF levels in unstimulated HUVEC support the presumption of the pathophysiological links between these proteins. Of the tested heparin formulas UFH seems to be the most potent in altering the OPG, RANKL and vWF axis

Safety of intravenous ferric carboxymaltose versus oral iron in patients with nondialysis-dependent CKD: an analysis of the 1-year FIND-CKD trial.

Background: The evidence base regarding the safety of intravenous (IV) iron therapy in patients with chronic kidney disease (CKD) is incomplete and largely based on small studies of relatively short duration. Methods: FIND-CKD (ClinicalTrials.gov number NCT00994318) was a 1-year, open-label, multicenter, prospective study of patients with nondialysis-dependent CKD, anemia and iron deficiency randomized (1:1:2) to IV ferric carboxymaltose (FCM), targeting higher (400-600 µg/L) or lower (100-200 µg/L) ferritin, or oral iron. A post hoc analysis of adverse event rates per 100 patient-years was performed to assess the safety of FCM versus oral iron over an extended period. Results: The safety population included 616 patients. The incidence of one or more adverse events was 91.0, 100.0 and 105.0 per 100 patient-years in the high ferritin FCM, low ferritin FCM and oral iron groups, respectively. The incidence of adverse events with a suspected relation to study drug was 15.9, 17.8 and 36.7 per 100 patient-years in the three groups; for serious adverse events, the incidence was 28.2, 27.9 and 24.3 per 100 patient-years. The incidence of cardiac disorders and infections was similar between groups. At least one ferritin level ≥800 µg/L occurred in 26.6% of high ferritin FCM patients, with no associated increase in adverse events. No patient with ferritin ≥800 µg/L discontinued the study drug due to adverse events. Estimated glomerular filtration rate remained the stable in all groups. Conclusions: These results further support the conclusion that correction of iron deficiency anemia with IV FCM is safe in patients with nondialysis-dependent CKD

Oxidative Storm Induced by Tryptophan Metabolites: Missing Link between Atherosclerosis and Chronic Kidney Disease

Chronic kidney disease (CKD) occurrence is rising all over the world. Its presence is associated with an increased risk of premature death from cardiovascular disease (CVD). Several explanations of this link have been put forward. It is known that in renal failure, an array of metabolites cannot be excreted, and they accumulate in the organism. Among them, some are metabolites of tryptophan (TRP), such as indoxyl sulfate and kynurenine. Scientists have become interested in them in the context of inducing vascular damage in the course of chronic kidney impairment. Experimental evidence suggests the involvement of TRP metabolites in the progression of chronic kidney disease and atherosclerosis separately and point to oxidative stress generation as one of the main mechanisms that is responsible for worsening those states. Since it is known that blood levels of those metabolites increase significantly in renal failure and that they generate reactive oxygen species (ROS), which lead to endothelial injury, it is reasonable to suspect that products of TRP metabolism are the missing link in frequently occurring atherosclerosis in CKD patients. This review focuses on reports that shed a light on TRP metabolites as contributing factors to vascular damage in the progression of impaired kidney function