Clinical features and outcomes in patient with antineutrophil cytoplasmic autoantibody-positive glomerulonephritis associated with propylthiouracil treatment in Siriraj Hospital.

BACKGROUND: ANCA is detected in several vasculitic diseases, including drug-induced systemic vasculitis: propylthiouracil (PTU), hydralazine, minocycline, penicillamine, allopurinol, procainamide, carbimazole, thiamazole, clozapine and phenytoin. All have been known to induce ANCA positive vasculitis in adult patients. OBJECTIVE: To study the clinical manifestation, renal pathology and outcome of patients with ANCA positive vasculitis associated with propylthiouracil treatment in Siriraj Hospital. MATERIAL AND METHOD: Retrospective study in 7patients with Graves' disease who were treated with propylthiouracil and developed ANCA-positive glomerulonephritis between 2000-2008. RESULTS: Seven cases with Graves' disease who received propylthiouracil whose ages were 43 +/- 14 years. The duration of propylthiouracil treatment was 68.5 +/- 39 months and the doses were 50-150 mg per day. Six cases had P-ANCA and one case had C-ANCA in the serum. Proteinuria ranged from 0.49-2.9 gram per day. Mean serum creatinine was 2.05 mg/dl with creatinine clearance of 44 +/- 35 ml/min. The propylthiouracil was withdrawn in every patient and corticosteroid was administered. Renal remission was found until 1 year of follow-up. CONCLUSION: ANCA positive glomerulonephritis associated with propylthiouracil is not uncommon. The average onset of glomerulonephritis is 2 years or more. The propylthiouracil dosage was not necessary high. Urinalysis and other glomerulonephritis symptoms should be screened for early diagnosis and appropriate treatment in patients treated with PTU.

Malnutrition-inflammation score associated with atherosclerosis, inflammation and short-term outcome in hemodialysis patients.

BACKGROUND: Malnutrition-Inflammation Score (MIS) has been proposed as a new quantitative system for assessment of malnutrition and inflammation, which are common important risk factors for increased morbidity and mortality in maintenance hemodialysis (MHD) patients. OBJECTIVE: To determine the MIS and related it to the presence of atherosclerosis, and the morbidity and mortality rate. MATERIAL AND METHOD: The inflammatory and nutritional status in 100 MHD patients was evaluated by serum high-sensitivity C-reactive protein (hs-CRP), Subjective Global Assessment (SGA), and MIS. Atherosclerosis was defined by a history of cardiovascular disease or presence of carotid plaque by B-mode ultrasonography. Twelve-month prospective hospitalization and mortality rates were recorded. RESULTS: The MIS score was significantly higher in patients with atherosclerosis (5.5 +/- 2.3 vs. 3.0 +/- 1.7, p = 0.003) and modestly correlated with serum ferritin level (r = 0.304, p = 0.03), but did not correlated with hs-CRP. The SGA was not associated with hs-CRP level and atherosclerosis. Over a 12-month follow-up period, 4 patients died and 28 were hospitalized at least once. Compared to the survivor group, MIS in the deceased group was significantly higher (8.0 +/- 1.4 vs. 5.1 +/- 2.3, p = 0.01) while SGA, hs-CRP and other biochemical markers were not significantly different. The Receiver Operating Characteristics Curves for the prediction of 1-year mortality from the MIS score identified the optimal cut-off value of 7.5 with sensitivity of 75% and specificity of 88%. There was no association between MIS or SGA and hospitalization. CONCLUSION: MIS is a useful tool for the assessment of malnutrition and inflammatory status. It is superior to the conventional SGA as a predictor of short-term outcome in MHD patients.

Prevalence of chronic kidney disease in Thai adults: a national health survey.

BACKGROUND: The prevalence of patients with end stage renal disease (ESRD) who need dialysis and/or transplantation has more than doubled in Thailand during the past two decades. It has been suggested that therapeutic strategies to reduce the risk of ESRD and other complications in CKD are now available, thus the early recognition and the institution of proven therapeutic strategies are important and beneficial. We, therefore, aimed to determine the prevalence of CKD in Thai adults from the National Health Examination Survey of 2004. METHODS: Data from a nationally representative sample of 3,117 individuals aged 15 years and older was collected using questionnaires, physical examination and blood samples. Serum creatinine was measured by Jaffé method. GFR was estimated using the Chinese modified Modification of Diet in Renal Disease Study equation. Chronic kidney Disease (CKD) stages were classified based on Kidney Disease Outcome Quality Initiative (K/DOQI). RESULTS: The prevalence of CKD in Thai adults weighted to the 2004 Thai population by stage was 8.1% for stage 3, 0.2% and 0.15% for stage 4 and 5 respectively. Compared to non-CKD, individuals with CKD were older, had a higher level of cholesterol, and higher blood pressure. Those with cardiovascular risk factors were more likely to have CKD (stage 3-5) than those without, including hypertension (OR 1.6, 95%CI 1.1, 3.4), diabetes (OR 1.87, 95%CI 1.0, 3.4). CKD was more common in northeast (OR 2.1, 95%CI 1.3, 3.3) compared to central region. Urinalysis was not performed, therefore, we could not have data on CKD stage 1 and 2. We have no specific GFR formula for Thai population. CONCLUSION: The identification of CKD patients should be evaluated and monitored for appropriate intervention for progression to kidney disease from this screening.

Arterial occlusion in nephrotic syndrome: report of four cases in Siriraj Hospital.

Venous thrombosis is commonly found in nephrotic syndrome, but arterial occlusion is never report in Thailand. Four cases with cerebral and femoral arteries occlusion were demonstrated. The early diagnosis and appropriate intervention can improve outcomes, reduce mortality and morbidity significantly.

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.

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.

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.