The effect of alpha-tocopherol on the oxidative stress and antioxidants in idiopathic IgA nephropathy.

OBJECTIVE: Nearly 25% of IgA nephropathy patients progress to end-stage renal disease over a 20-25 year follow-up period. IgA containing immune complex stimulates oxygen free radical production by mesangial cells in vitro, which may mediate glomerular injury in this disorder. Therefore, we studied whether dietary supplementation with the antioxidant agent, vitamin E, attenuates renal damage in patients with IgA nephropathy. MATERIAL AND METHOD: Twenty-eight patients with idiopathic IgA nephropathy were supplemented with vitamin E 400 mg/day for 6 months. Antioxidant enzymes, glutathione, plasma malondialdehyde (MDA), and renal function were studied after 3 and 6 months therapy. RESULT: The result of the study showed high plasma MDA and significant reduction after therapy (1.15 +/- 0.45 VS 0.86 +/- 0.30 microM, p < 0.0001). The RBC vitamin E was also elevated statistically significantly (5.07 +/- 2.42 VS 15.70 +/- 3.37 microM, p < 0.001). Glutathione peroxidase activities were decreased (38.52 +/- 15.53 VS 23.97 +/- 7.63 U/gHb, p < 0.001). Glutathione was also decreased (44.80 +/- 9.70 VS 32.45 +/- 6.74 mg/dl, p < 0.05) but there were no changes in red cell catalase and superoxide dismutase activities. Creatinine clearance, proteinuria, urine N-acetyl glucosaminidase and beta2-microglobulin also showed no improvement. CONCLUSION: Our data demonstrated the particular group of IgA nephropathy patients with low vitamin E level and high oxidative stress had significant reduction of oxidative stress after vitamin E therapy.

Effect of short-term folate and vitamin B supplementation on blood homocysteine level and carotid artery wall thickness in chronic hemodialysis patients.

OBJECTIVE: Hyperhomocysteinemia is an independent risk factor for atherosclerotic vascular disease in chronic hemodialysis patients. This stratified randomized controlled trial was designed to measure the effect of high dose oral vitamin B6, vitamin B12, and folic acid on homocysteine levels, and to evaluate the effect on atherosclerosis as measured by Intima-Media Thickness (IMT) of carotid arteries. MATERIAL AND METHOD: Fifty-four chronic hemodialysis patients with hyperhomocysteinemia were randomized to receive oral 15 mg folic acid, 50 mg vitamin B6, and 1 mg vitamin B12 daily (treatment group) or oral 5 mg folic acid alone (control group) for 6 months. Homocysteine level and IMT were measured in both groups. RESULTS: At 6 months, homocysteine levels in the treatment group were significantly reduced from 27.94 +/- 8.54 to 22.71 +/- 3.68 mmol/l (p = 0.009) and were not significantly increased from 26.81 +/- 7.10 to 30.82 +/- 8.76 mmol/l in control group (p = 0.08). Mean difference between both groups was statistically significant (p = 0.002). There was no significant difference of IMT of carotid arteries, however, a tendency that the treatment group would have less thickness was observed (0.69 +/- 0.29 mm and 0.62 +/- 0.16 mm, p = 0.99). CONCLUSION: Treatment of hyperhomocysteinemia in chronic hemodialysis patients with daily oral 15 mg folic acid, 50 mg vitamin B6, and 1 mg vitamin B12 for 6 months decreases homocysteine levels and tends to reduce IMT of carotid arteries. A long term study for the prevention of atherosclerosis is warranted.

Relationship between hyperhomocysteinemia and atherosclerosis in chronic hemodialysis patients.

BACKGROUND: Hyperhomocysteinemia is an independent risk factor of coronary artery heart disease (CAHD) and atherosclerosis in a normal population. However, it is still controversial in end-stage kidney disease patients who underwent long-term dialysis. Carotid intima-media thickness (IMT) is the standard non-invasive measurement of atherosclerosis. The aims of the present study were to determine the homocysteine (Hcy) level, and to evaluate its role as a risk factor of atherosclerosis in hemodialysis (HD) patients. MATERIAL AND METHOD: Clinical data and blood chemistries were assayed in 62 HD patients. Atherosclerosis was defined by clinical presentations of CAHD, cerebrovascular or peripheral vascular diseases, or carotid plaque by ultrasound. IMT was also measured by ultrasound RESULTS: Plasma Hcy level in HD patients was significantly higher in HD patients than normal controls (28.3 +/- 8.3 vs 9.7 +/- 2.9 micromol/l, p < 0.001). Older age (p < 0.001), male sex (p = 0.05), longer duration of HD (p = 0.05), and higher plasma Hcy level (p = 0.01) correlated with atherosclerosis by univariate analysis, but plasma Hcy did not show significant correlation by multivariable analysis. There was also correlation between IMT and atherosclerosis in HD patients (p < 0.001) but no correlation was observed between plasma Hcy level and lMT. CONCLUSION: Hyperhomocysteinemia is not an independent factor in the genesis of atherosclerosis in HD patients. Advanced age plays a major role of hyperhomocysteinemia and IMT is a useful marker of atherosclerosis in these patients.

Effect of fish oil on oxidative stress, lipid profile and renal function in IgA nephropathy.

The omega-3 polyunsaturated fatty acids in fish oil have been shown to produce beneficial effects, such as a reduction in blood pressure, proteinuria, lipid levels and inflammation. Aggregated immunoglobulin A obtained from IgA nephropathy patients induced greater oxygen free radicals in polymorphonuclear leukocytes than other glomerulopathy. All of which may affect the course of IgA nephropathy. Twenty-three adult patients with biopsy proven IgA nephropathy, with proteinuria more than 1 g/day, serum creatinine less than 3 mg/dl and blood pressure control less than 130/80 mmHg were given omega-3 polyunsaturated fatty acids (PUFA) in the form of an Omacor capsule 4 g/day equivalent to eicosapentaenoic acid (EPA) 1.88 g and docosahexaenoic acid (DHA) 1.48 g for 6 months. A 3 to 6 month follow-up was planned, with monthly evaluations of the patients. By six months, the serum triglyceride was significantly reduced (143.45 +/- 62.65 vs 91 +/- 42.89 mg/dl, p = 0.002), serum cholesterol was also reduced but not statistically significant (234.16 +/- 56.29 vs 219.76 +/- 51.25 mg/dl, p = 0.07). There was a trend of increased serum high density lipoprotein (HDL)-cholesterol (39.26 +/- 10.56 vs 42.72 +/- 8.37 mg/dl, p = 0.056). Urine beta-2-microglobulin was elevated in IgA patients and decreased statistically significant after 3 months (453 +/- 580 vs 308 +/- 274 microg/24 h, p < 0.001) and 6 months of fish oil therapy (453 +/- 580 vs 142 +/- 182, p < 0.03) while urine N-acetyl-glucosaminidase (NAG) was of no significant difference both before and after fish oil administration (21 +/- 10 vs 22 +/- 10 and 21 +/- 9 U/24 h, p = 0.08). Plasma malondialdehyde (MDA), the end product of oxidative stress was statistically, significantly decreased (1.09 +/- 0.51 vs 0.89 +/- 0.49 nmol/L, p = 0.003). The study did not show any change in blood pressure, proteinuria, or serum creatinine. The authors conclude from the results of this study that patients with idiopathic IgA nephropathy with proteinuria and mildly reduced GFR did not benefit from short-term treatment with 4 g per day of omega-3 PUFA regarding the total protein excretion and glomerular filtration rate (GFR), but the advantage was the improvement in tubular dysfunction, lipid profiles, and oxidative stress.

Cyclosporine monitoring in patients with renal, cardiac and bone marrow transplants: A comparison between clone enzyme donor immunoassay and fluorescence polarization immunoassay methods.

In the present study a new method for selectively determining parent cyclosporine in whole blood, a clone enzyme donor immunoassay (CEDIA; Boehringer Mannheim), was compared with a fluorescence polarization immunoassay (FPIA; TDxAbbott). A total of 429 samples were collected, comprising 371 renal, 34 cardiac, 14 bone marrow and 10 corneal transplant recipients. Regression equations in 429 samples is CEDIA cyclosporine (ng/mL) = 0.999 x FPIA (ng/mL) + 1.684, (r=0.997). The linearity analysis was done from 0 – 1,000 ng/mL, which gave a good analytical range of between 15-600 ng/mL. The new CEDIA method also has within-rin CV = 1.77 – 3.69 percent which is better than the FPIA method (2.20 – 6.10 percent). The advantages of the new CEDIA method are the lower cost of the reagents and the fact that there is no need to purchase a new automated clinical chemistry analyser since it can be applied to routine chemistry instruments immediately after the reagents become available to the laboratory.

Adenosis Deaminase (ADA) activity in tuberculous and in carcinomatous lungs.

Determination of ADA activity in BALF was carried out in 12 patients with active pulmonary tuberculosis, 12 patients with bronchogenic carcinoma and 11 healthy volunteers. Pertinent findings were: (1) ADA activity increased significantly only in tuberculous lungs; and (2) ADA activity in diseased lungs was significantly higher than in apparently non-diseased lungs. The latter findings may reflect the difference in local cellular activity and proliferation rate between the diseased and non-diseased lungs.