Abnormal kinetics of erythrocyte sodium lithium countertransport in patients with diabetic nephropathy in Thailand.

BACKGROUND: In essential hypertension and diabetic nephropathy, sodium-lithium counter transport (Na/Li CT) is an inherited marker for metabolic influences of cardiovascular risk. The kinetics of Na/Li CT are modified by two types of thiol group in the membrane. In choline medium, the type 1 thiol reacts with N-ethtyl maleimide (NEM) to cause a decrease in Km and increase Vmax/Km ratio. However in the presence of external Na or Li both the type 1 or type 2 thiols react so that both Km and Vmax are reduced. Low Km of Na/Li CT has been previously reported to be a major abnormality in diabetic nephropathy (DN) and can be used to identify diabetic patients who are at high risk for DN. A recent study showed that the type 1 thiol protein controlling the Km of Na/Li CT was a 33-kD protein and the gene for this protein is going to be cloned. OBJECTIVE: The authors sought to identify Na/Li CT kinetic abnormalities in Type 2 diabetes in Thai patients. MATERIAL AND METHOD: Erythrocyte Na/Li CT kinetics and their modulation by thiol proteins were measured in erythrocytes from 22 patients with Type 2 diabetes and 42 normal control subjects. RESULTS: The kinetics of Na/Li CT in untreated erythrocytes were similar Thiol protein alkylation with NEM generally caused both Vmax and Km to fall, but caused Km to rise in erythrocytes of diabetic patients, whose native Km was low. Thus, abnormalities in the regulation of Na/Li CT by key thiol proteins were found in about one-third of subjects with Type 2 diabetes in Thailand. CONCLUSION: Membrane abnormalities may indicate a common pathway of pathological mechanism found in essential hypertension and diabetic nephropathy and may be used as a phenotype for further genetic studies of this transporter.

An analysis of 3,555 cases of renal biopsy in Thailand.

BACKGROUND: The knowledge of the epidemiology of biopsied renal diseases provides useful information in clinical practice. There are several epidemiologic population-based studies of biopsy-proven nephropathies with detailed clinicopathologic correlations that could be different according to the country analyzed. OBJECTIVE: To identify the prevalence of primary and secondary glomerular diseases and to study the trend of the pattern changes of the glomerulopathy in Thailand. MATERIAL AND METHOD: A retrospective study of percutaneous renal biopsies during a 23-year period of 1982 to 2005 was performed. A total of 3,555 consecutive native kidney biopsies in adult patients between 12 and 84 years of age were analyzed for the prevalence and changes in the 5-year interval over the two decades. RESULTS: From the clinical trial of 3,275 patients, the ratio between primary and secondary glomerular diseases was 2:1 (2154:1121). The most common primary glomerular disease (2154 patients) were IgM nephropathy (n = 986, 45.8%) followed by IgA nephropathy (n = 386, 17.9%); membranous nephropathy (n = 341, 15.8%); diffuse endocapillary proliferative glomerulonephritis (n = 114, 5.3%) and diffuse crescentic glomerulonephritis (n = 71, 3.3%). Lupus nephritis was the most prevalent cause of secondary glomerulonephritis in the present study (n = 992, 88.5%). Examination of the 5-year interval along the study period revealed a significant increase in the prevalence of IgA nephropathy and diabetic nephropathy. Prevalence of focal and segmental glomerulosclerosis rose by five times over the last two decades in contrast to IgM nephropathy, which prevalence is decreasing. CONCLUSION: There is high prevalence of IgM nephropathy, IgA nephropathy, and lupus nephritis in Thailand which is different from other countries. It could be due to various races and altered environments. The information obtained from these results is an important contribution for the understanding of the prevalence in renal diseases in Thailand. It can be used as the baseline data for making efficient research into the appropriate and beneficial way of management in the future.

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.

Factors associated with complications and adequacy of percutaneous kidney biopsy.

Objective: Percutaneous kidney biopsy (PKB) is an essential procedure in practical nephrology. However, it may cause serious complications, especially in high-risk patients. To determine the factors associated with the complications and the adequacy of PKB under ultrasonic guidance. Methods: Patients were stratified according to serum creatinine (SCr) and randomized for needle types (spring-loaded automatic gun and Tru-cut needle), diameters (16G vs 18G) and the effect of compression at biopsy site. The patients were observed for major (bleeding requiring a blood transfusion or intervention) and minor (not requiring intervention) complications. Results:The patients with serum creatinine (SCr) < 4.0 mg/dl (n=133) had significantly lower complications than those with SCr  4.0 mg/dl (n=35), both major (2 [1.5%] vs. 5 [14.3%]) and minor (6 [4.5%] vs. 3 [8.5%]). All complications occurred within 48 hours (93.8% within 24 hours). In group A, no significant difference in complications was found in needle types, axes, diameters and compression at the biopsy site, including numbers of puncture (< 6 times), length of tissue, kidney size and echogenicity. All samples except two were adequate for diagnosis, with an average of 13 glomeruli. There was no significant difference in tissue adequacy ( 10 glomeruli) in needle types and diameters, but the failure rate and number of puncture were higher with the Tru-cut needle (p < 0.01). Conclusion: The needle type and size or compression at the puncture site do not affect the complication after PKB under ultrasonic guidance, whereas a SCr 4.0 mg/dl is an important factor of the complications but there is no effect on the adequacy of the renal tissues.