The relationship between the antioxidant system, oxidative stress and dialysis-related amyloidosis in hemodialysis patients.

End-stage renal disease (ESRD) is associated with several complications that are partly due to excess amounts of reactive oxygen species and/or decreased antioxidant activity. Dialysis-related amyloidosis (DRA) has also been linked to increased oxidative stress. The aim of this study was to investigate the relationships between the antioxidant system, including superoxide dismutase (SOD), malonyldialdehyde (MDA), various biochemical parameters and shoulder amyloidosis, in hemodialysis patients. We studied 107 non-diabetic chronic dialysis patients. The SOD levels correlated with right and left biceps tendon thickness (r = -0.219, P = 0.048 and r = -0.236, P = 0.031, respectively), MDA (r = -0.429, P = 0.000) and albumin levels (r = -0.319, P = 0.001). MDA levels correlated with right and left biceps thickness (r = 0.291, P = 0.006 and r = 0.337, P = 0.001, respectively) and ß2 microglobulin levels (r = 0.455, P = 0.000). We also identified the statistically significant relationships between MDA levels and supraspinatus tendon thickening (greater than 7 mm) and right and left biceps tendon thickness (P = 0.022, P = 0.040 and P = 0.005, respectively). Our data suggest the complex relationship between antioxidants and oxidative stress and further support the roles of oxidative stress and antioxidants in DRA.

The effect of hemodialysis on accelerated atherosclerosis in diabetic patients: correlation of carotid artery intima-media thickness with oxidative stress.

OBJECTIVE: Both diabetes and hemodialysis (HD) are associated with increased oxidative stress. The aim of this study was to clarify the effect of maintenance HD on oxidative stress parameters in diabetic patients and to explore any relation between carotid artery intima-media thickness (CIMT) and oxidative stress markers. METHODS: Twenty Type 2 diabetic patients undergoing chronic maintenance HD, 20 type 2 diabetic patients with normal renal function, and 20 age- and sex-matched healthy subjects were included. Serum thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCO), and nitrite/nitrate levels were determined as oxidative stress markers. Serum vitamin E, plasma sulfhydryl (P-SH), erythrocyte glutathione (GSH) levels, and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were measured as antioxidants. CIMT was assessed by carotid artery ultrasonography. RESULTS: Both diabetic patient groups had enhanced oxidative stress indicated by higher levels of TBARS, PCO, and nitrate/nitrite and lower activities of SOD, CAT, and GPx compared to controls. Diabetic patients undergoing HD had significantly higher CIMT (P=.001) and higher levels of nitrite/nitrate (P=.05), PCO (P=.03), and GSH (P=.04) but significantly lower levels of P-SH (P<.001), serum vitamin E (P=.04), SOD (P=.02), CAT (P=.001), and GPx (P=.006) compared to diabetic patients with normal renal functions. There were significant negative correlations between CIMT and SOD (r=-0.50, P<.001), CAT (r=-0.41, P=.003), and P-SH levels (r=-0.51, P<.001) and significant positive correlation between CIMT and nitrite/nitrate levels (r=0.41, P=.003) and TBARS (r=0.35, P=.02). Linear regression analysis showed TBARS was significantly and positively correlated with CIMT (P=.04), while SOD and P-SH were significantly and negatively correlated with CIMT (P=.05 and P=.02, respectively). CONCLUSIONS: Hemodialysis exacerbates oxidative stress and disturbances in antioxidant enzymes in diabetic patients. Serum nitrite/nitrate and TBARS can be used as positive determinants, while erythrocyte SOD, CAT activities, and P-SH level can be used as negative determinants of atherosclerosis assessed by CIMT in diabetic patients.

Are uremia, diabetes, and atherosclerosis linked with impaired antioxidant mechanisms?

BACKGROUND: Oxidative stress is a new risk factor for atherosclerosis. Increased oxidative stress in hemodialysis (HD) patients may arise from uremia-associated metabolic/humoral abnormalities and bioincompatibility of dialysis. Patients with diabetes mellitus (DM) may be subject to an additional risk. Respective influences of uremia, diabetes, and HD duration in accelerated atherosclerosis and oxidative stress have not been clarified yet. METHODS: The study was performed on 24 nondiabetic HD patients, 23 diabetic HD patients, 20 stages 3 to 4 chronic kidney disease patients, and 21 diabetic patients without overt nephropathy. Carotid intima-media thickness, a surrogate of atherosclerosis, was measured by high-resolution B-mode ultrasonography. Oxidant status was determined by lipid peroxidation as expressed by malondialdehyde (MDA); antioxidant status was determined by superoxide dismutase, catalase, glutathione peroxidase, reduced intracellular glutathione, and plasma thiol. RESULTS: Intima-media thickness (IMT) was higher in patients undergoing HD but not different between nondiabetic HD patients and diabetic HD patients. No correlation was found between the duration of HD and intima-media thickness. Antioxidants were generally lower in HD patients. Intima-media thickness was positively correlated with MDA and negatively correlated with plasma thiol. Among other risk factors, only age was correlated with intima-media thickness. CONCLUSIONS: Increased carotid IMT in HD patients is independent of duration of HD or diabetes status. Age and MDA are the significant predictors of carotid IMT. Increased oxidative stress due to impaired antioxidant mechanisms, particularly reduced plasma thiol redox potential, may account for accelerated atherosclerosis in high-risk patients with chronic kidney failure and/or DM.

Carotid artery intima-media thickness correlates with oxidative stress in chronic haemodialysis patients with accelerated atherosclerosis.

BACKGROUND: Accelerated atherosclerosis is the major cause of mortality in patients on chronic haemodialysis (HD). Increased oxidative stress might be the major factor leading to high cardiovascular mortality rate in HD patients. The aim of our study was to clarify effects of uraemia and dialysis on oxidative stress parameters and explore the relation between oxidative stress markers and carotid artery intima-media thickness (CIMT) as an indicator of atherosclerosis. METHODS: Twenty chronic HD patients, 20 predialytic uraemic patients and 20 healthy subjects were included in the study. Serum thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCO) and nitrite/nitrate levels were determined as oxidative stress markers. Serum vitamin E, plasma sulfhydryl (P-SH), erythrocyte glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities were measured as antioxidants. CIMT was assessed by carotid artery ultrasonography. RESULTS: Both chronic HD and predialytic uraemic patients had enhanced oxidative stress indicated by higher levels of nitrite/nitrate, TBARS and PCO, and lower levels of P-SH, SOD, CAT and GPx compared to controls. HD patients had significantly higher CIMT and nitrite/nitrate while significantly lower P-SH,vitamin E, SOD, CAT and GPx compared to predialytic uraemic patients. There was a significant positive correlation between CIMT and TBARS (r = 0.38, P = 0.003) and nitrite/nitrate levels (r = 0.41, P = 0.001), while there was a significant negative correlation between CIMT and SOD (r = -0.35, P = 0.01), CAT (r = -0.65, P < 0.001) and P-SH levels (r = -0.50, P < 0.001). A linear regression analysis showed that TBARS were still significantly and positively correlated with CIMT (P = 0.001), while CAT and P-SH were significantly and negatively correlated with CIMT (P = 0.002 and P = 0.048, respectively). CONCLUSIONS: HD exacerbates oxidative stress and disturbances in antioxidant enzymes in uraemic patients. We propose that serum TBARS and nitrite/nitrate can be used as positive determinants, while erythrocyte SOD, CAT and P-SH may be used as negative determinants of atherosclerosis assessed by CIMT in uraemic and HD patients.