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The prevalence of cardiovascular disease in patients with renal failure is extremely high and accounts for a large part of the morbidity and mortality. Inflammation participates importantly in host defense against infectious agents and injury, but also contributes to the pathophysiology of many diseases, including cardiovascular atherosclerosis, which is a main problem in patients with renal failure. Recruitment of blood leukocytes to the injured vascular endothelium characterizes the initiation and progression of atherosclerosis and involves many inflammatory mediators, modulated by cells of both innate and adaptive immunity. Excessive inflammatory and immune responses, communicated by these different cell types, are driven by inflammatory cytokines that promote associated tissue damage if cytokine signaling pathways remain unregulated. Thus, pathways capable of suppressing proinflammatory cytokine signaling hold the potential to limit life-threatening cardiovascular events caused by atherogenesis. Suppressor of cytokine signaling (SOCS) are a family of intracellular proteins, several of which have emerged as key physiological regulators of cytokine-mediated homeostasis, including innate and adaptive immunity. Accumulating evidence supports the idea that dysregulation of cytokine signaling by differential SOCS expression is involved in the pathogenesis of various inflammatory, and immunological diseases, including atherosclerosis. Based on recent observations, in which SOCS expression levels are profoundly altered in kidney disease, we discuss the possibilities of SOCS as new intracellular markers of inflammation as well as their potential atherogenic properties in renal failure related cardiovascular disease.
The pathological process in the kidneys in the course of chronic renal failure (CRF) leads to multiple metabolic disturbances in the whole body. Disturbances of protein, carbohydrate, fat, electrolyte and calcium-phosphate balance are the main reasons for protein-energy malnutrition in patients. The use of a proper, individually adapted diet may slow down the progression of the disease and reduce the intensity of the symptoms.
Oxidative stress is at play in the progression of chronic renal failure (CRF) and in the genesis of atherosclerosis. The aim of the present study was to evaluate the factors that might influence the oxidative-antioxidative balance in patients on hemodialysis. The study group consisted of 71 hemodialysis patients due to CRF. Sixteen healthy subjects constituted a control group. The levels of 8-hydroxy-2’-deoxyguanosine (8-OHdG), C-reactive protein (CRP), and the blood lipid profile were measured in both groups. The results showed significantly higher mean levels of both 8-OHdG and CRP in the hemodialysis patients compared with that in the control subjects. The highest level of 8-OHdG was found in the subgroups of the patients with CRF primarily caused by diabetes (16.4 ng/ml) and with hypertensive nephropathy (15.8 ng/ml). More than a 2.5-fold higher level of 8-OHdG in the hemodialysis patients compared with the control subjects points to the presence of intensive oxidative stress in the patients.
The properties of red blood cell membranes in patients with chronic renal failure were investigated using electron paramagnetic resonance spectroscopy. Using spin traps, 5,5-dimethylpirroline-l-oxide and N-tert-butyl-a-phenylni- trone, we found generation of hydroxyl radicals in the blood of patients with chronic renal failure after 20 min of regular hemodialysis. The physical state of membrane proteins and membrane osmotic fragility and reductive properties of red blood cells were studied. The increase in the relative correlation time of 4-(2-iodoacetamido)-2,2,6,6-tetramethylpiperidine-l-oxyl in­dicates the immobilization of membrane protein molecules in erythrocytes of chronic renal failure patients. The decrease in membrane protein mobility was observed in whole blood incubated with tert-butylhydroperoxide, regardless of the presence of iron. We found that the addition of ferrous ions did not aggravate profound changes in membrane proteins induced with tert-butylhy­droperoxide. We also demonstrated higher osmotic fragility of erythrocytes in the patients with renal failure as compared to normal subjects.
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