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.

Efficacy of intradermal hepatitis B vaccination compared to intramuscular vaccination in hemodialysis patients.

BACKGROUND: Hepatitis B virus infection remains an important problem in hemodialysis patients. Only 50 to 60% of the patients develop seroconversion (anti-HBs Ab titer > 10 IU/L) after intramuscular hepatitis B vaccination. Small dose intradermal inoculation method of hepatitis B vaccine has been reported to be effective as well as economical, and could provide rapid seroconvesion of immunity. The aim of the present study was to compare the efficacy of intradermal hepatitis B vaccination with intramuscular vaccination in hemodialysis patients. MATERIAL AND METHOD: Fifty one hemodialysis patients were randomly assigned to two groups, 25 patients received a total 7 doses of 10 mmicrog of recombinant hepatitis B vaccine (Engerix B) intradermally every 2 weeks (ID group), whereas 26 patients received 40 microg intramuscularly at 0, 1, 2 and 6 months (IM group). Anti-HBs Ab titer was measured at 2, 3, 4 and 7 months after the first vaccination in both groups. Vaccination responses were classified into 3 subgroups according to anti-HBs Ab titer and these included excellent response (> 1,000 IU/L), good response (10-999 IU/L) and non-response (< 10 IU/L). RESULTS: The seroconversion rates at 2, 3, 4, and 7 months in the ID group were 56%, 76%, 88%, and 92% compared with 31%, 42%, 65%, and 69% in the IM group, respectively. Only the seroconversion rates at 3 months were significantly higher in the ID group (76% versus 42%, p = 0.03). At 7 months after the first vaccination, good and excellent responders in the ID group were 72% (18/25) and 20% (5/25) compared with 34.5% (9/26) and 34.5% (9/26), respectively (p > 0.05). Only minor side effects were observed. CONCLUSION: Seven doses of 10 mg intradermal vaccination induced a high seroconversion rate and were comparable with intramuscular regimen. Intradermal vaccination may be helpful for the rapid induction of protective level of antibodies and may be a cost-saving alternative to intramuscular vaccination in hemodilaysis patients.

Effect of diltiazem on the pharmacokinetics of microemulsion cyclosporine A in renal transplantation.

OBJECTIVE: Diltiazem might be used as a cyclosporine A (CsA)-sparing agent. There is evidence that CsA (C2) level is the best single point blood sampling for monitoring the CsA level. The authors, therefore, studied the effect of diltiazem on the pharmacokinetics (PK) of CsA, including C2, in renal transplant patients. MATERIAL AND METHOD: Twenty-five CsA-treated renal transplant patients, with neither diseases nor agents that alter the PK of CsA, were enrolled in the present study. The PK of CsA was studied in all patients before and 2 weeks after taking diltiazem. RESULTS: The area under the concentration-time curve (AUC) of CsA was obtained by 2 methods, AUC0-4 and AUC0-12. Before taking diltiazem, the correlation (r) between C0 with AUC0-4 and C0 with AUC0-12 were 0.799 and 0.871, respectively (p = 0.01), r between C2 with AUC0-4 and C2 with AUC0-12 were 0.988 and 0.956, respectively (p = 0.01). Time to maximum concentration (Tmax) of CsA was at 1.5 hr (1.5-4.0 hr) [median (range)]. After two weeks of taking diltiazem, r between C0 with AUC0-4 and C0 with AUC0-12 were 0.577 and 0.784, respectively (p = 0.01), r between C2 with AUC0-4 and C2 with AUC0-12 were 0.988 and 0.896, respectively (p = 0.01). Tmax of CsA was at 1.5 hr (1.5-4.0 hr) [median (range)]. The dosage of CsA could be reduced by 25.8% to maintain the same levels of C0 and C2 in the same patients after taking diltiazem. CONCLUSION: Diltiazem slightly altered the correlation between C2 with AUC of CsA. This indicates that C2 is the best single point blood sampling to monitor the therapeutic levels of CsA in renal transplant patients who are taking diltiazem.

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.

Circulating N-terminal pro-brain natriuretic peptide and cardiac troponin T in chronic dialysis patients.

In the general population, plasma concentrations of cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptides (NT-proBNP) are useful as markers of cardiac ischemia and heart failure respectively. Whether these cardiac markers have similar diagnostic potential in chronic dialysis patients are not known. The authors studied the diagnostic value of cTnT and NT-proBNP correlated with the clinical status of 63 chronic renal failure (CRF) patients with chronic dialysis (30 males and 33 females), aged 26 to 77 years (mean +/- SD, 55.9 +/- 12.6 years). Plasma cTnT and NT-proBNP were determined by using Elecsys 2010 (Roche, Switzerland). The authors found that 23.8 per cent of the chronic dialysis patients had cTnT concentrations more than the cut-off (> or = 0.1 ng/ml) and 100 per cent of these patients had NT-proBNP concentrations over the cut-off (> 334 pg/ml). The authors could not demonstrate the statistical difference between males and females for NT-proBNP concentrations as reported in the general population. But cTnT concentrations in females were significantly less than males. The authors also found a weak correlation between the two markers, when the circulating cTnT was correlated with NT-proBNP. These results suggested that plasma cTnT in chronic dialysis patients should be a prognostic marker for cardiac ischemia by using the same cut-off as the normal population. However, plasma NT-proBNP concentrations could not be used as a heart failure marker in this group of patients and needed another cut-off value for specific use in chronic dialysis patients. Moreover, the combination of cTnT and NT-proBNP concentrations in these patients may be another choice for detection of both cardiac ischemia and heart failure in the same situation. These combination markers should improve mortality in chronic dialysis patients.

Determination of the apolipoprotein E genotype using PCR-RFLP in kidney diseases.

Using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP), genotypes of the apolipoprotein E (Apo E) were determined in 50 control subjects and 60 Thai kidney diseases patients including nephritic syndrome and chronic renal failure (CRF) (30 each). Exon 4 of the Apo E genomic DNA was amplified between nucleotide numbers 2849 and 3071 (270 base pairs) then digested with HhaI. It is observed that E3/3 was the most common genotype found in the control subjects (80%). In nephritic syndrome patients, E4/3 was found to be the most frequent (53.3%). On the contrary, E3/3 was found to be the most prominent in CRF patients (80%). There was a significant different of the Apo E genotype in hephrotic syndrome from the normal control subjects (p < 0.05 by X2 analysis). One the other hand, there was no significant difference of the Apo E genotype in CRF patients from the control subjects (p>0.5). Cholesterol and triglyceride levels of the E4/3 nephrotic syndrome patients were significantly different from the normal controls of the same genotype (p<0.05). Similarly, in CRF patients, triglyceride level of the E3/3 genotype was also significantly different from the normal controls of the same genotype (p<0.05). These results suggested that polymorphism of the Apo E genotypes may be associated with the lipid abnormalities in renal diseases.

Comparison between heat inactivation and DEAF trisacryl methods for the determination of urinary N-acetyl-ß- D-glucosaminidase isozyme in normal subjects and patients with glomerulonephritis.

We report a study on NAG-B isozyme determined by heat inactivation and DEAE trisacryl methods in 231 glomerulinepgriyis patients and normal subjects There was a good correlation between the NAG-B activities measured by both methods (r = 0.902). The NAG-B activity determined by DEAE trsacryl method was significantly higher than the heat inactivation method. The mean + SD NAG-B values of 58 normal Thai subjects, 69 Patients with idiopathic nephrotic syndrome and 50 with SLE were 0.30 + 0.23, 5.12 + 8.30 and 3.25 + 3.45 U/g creatinine respectively. There was no significant difference between sex and random single and 24 hour urine. The patients had a significantly higher NAG-B value than normal controls bur there was no difference between nephrotic syndrome and SLE. From our experience, NAG isozyme isozyme activity determination by this heat inactivation method is accurate, inexpensive, rapid and easy to perform, and therefore, it is a suitable procedure for NAG isozyme measurement.

Comparing two methods of determination of serum gentamicin level, HPLC with precolumn derivatization and EMIT in lidney diseased patients.

Therapeutic drug monitoring for serum Gentamicin is very useful for infectious patients. The most common methods for measuring concentration of Gentamicin in body fluids are microbiological assay, rasioimmunoassay (RIA), enzyme immunoassay (EMIT) and high pressure liquid chromatography (HPLC), The purpose of this study was to compare two new methods, an enzyme multiplied immunoassay test (EMIT; Suva Corp.) and high pressure liquid Chromatography with fluorescence detection precolumn derivatization, reversed Phase column. Forty serum samples were obtained from patients in the kidney disease unit, Department of Medicine, Siriraj Hospital. The two methods were evaluated on the basis of accuracy, limitation, specificity and cost. EMIT showed a high degree of accuracy and lesser limitation. But this method of HPLC could not determine values for serum gentamicin at levels below 4 ตg/ml. Total cost which included equipment for both procedures was similar. Unit cost for this method of HPLC was cheaper than EMIT but was time consuming and required experience. Both methods were specific for serum Gentamicin.