Endothelial dysfunction in patients with kidney failure and vascular risk factors: acute effects of hemodialysis.

BACKGROUND: Patients with kidney failure present endothelial dysfunction, which was shown to be partly corrected by hemodialysis. No data exist on the effects of hemodialysis on endothelial dysfunction in kidney failure patients with associated vascular risk factors. The aim of this study was to evaluate the acute effects of hemodialysis on endothelial dysfunction in patients with kidney failure and associated vascular risk factors and to assess the role of endothelium-toxic substances. METHODS: We assessed endothelial dysfunction in 13 patients with chronic renal failure and other vascular risk factors before and after hemodialysis and in 13 healthy controls and simultaneously measured nitric oxide (NO) synthesis and activity. Endothelial dysfunction was studied using an echographic method as flow-mediated dilation (FMD) of the brachial artery; plasma NO2- and NO3-, cyclic guanosine-5-monophosphate (cGMP), plasma homocysteine levels and low molecular mass-advanced glycation end-products (LMM-AGEs) were simultaneously measured. RESULTS: As compared with healthy controls, patients with renal failure showed a reduced FMD (2.89 +/- 1.43 vs. 7.81 +/- 1.54%, p < 0.01) which was not corrected by dialysis (after dialysis 2.40 +/- 1.65%, p = NS vs. pre). Plasma NO2- and NO3- were normal or slightly increased and remained unchanged after dialysis. Plasma cGMP levels were reduced and remained unchanged after dialysis. Homocysteine and LMM-AGE plasma levels were raised and, although significantly reduced by dialysis, remained higher than in controls. CONCLUSIONS: Patients with kidney failure and associated vascular risk factors show an endothelial dysfunction related to defective NO activity, which is not corrected by hemodialysis despite the reduction, though not to normal, in homocysteine and LMM-AGE levels. Endothelial dysfunction may contribute to the progression of atherosclerosis in patients with kidney failure and vascular risk factors.

Dermatan sulphate as an antithrombotic drug.

Dermatan sulphate (DS) is a glycosaminoglycan which selectively catalyzes the inactivation of thrombin by Heparin Cofactor II without interacting with Antithrombin III. DS does not interact with other coagulation factors and, unlike heparin, is able to inactivate thrombin bound to fibrin or to the surface of an injured vessel. Efficacy and safety of DS have been validated in studies on thromboprophylaxis and on the anticoagulation for hemodialysis. Studies on thromboprophylaxis have been performed in "medical" patients as well as in general, orthopedic and oncological surgery. In this last setting, DS proved to be more efficacious than heparin, in the absence of excess bleeding. No statistically significant differences were observed between DS and heparin in hemodialysis. A low-molecular-weight DS,which shows a higher bioavailability after s.c. administration, has been tested in pilot studies on the treatment of venous thromboembolism with encouraging results. Two DS-containing compounds, sulodexide and, particularly, mesoglycan, have been clinically studied in a number of trials and found to be effective in the treatment of venous and arterial leg diseases.