Dhavee Sirivongs

Thiazide Diuretics Exacerbate Fructose-Induced Metabolic Syndrome

Fructose is a commonly used sweetener associated with diets that increase the prevalence of metabolic syndrome. Thiazide diuretics are frequently used in these patients for treatment of hypertension, but they also exacerbate metabolic syndrome. Rats on high-fructose diets that are given thiazides exhibit potassium depletion and hyperuricemia. Potassium supplementation improves their insulin resistance and hypertension, whereas allopurinol reduces serum levels of uric acid and ameliorates hypertension, hypertriglyceridemia, hyperglycemia, and insulin resistance. Both potassium supplementation and treatment with allopurinol also increase urinary nitric oxide excretion. We suggest that potassium depletion and hyperuricemia in rats exacerbates endothelial dysfunction and lowers the bioavailability of nitric oxide, which blocks insulin activity and causes insulin resistance during thiazide usage. Addition of potassium supplements and allopurinol with thiazides might be helpful in the management of metabolic syndrome.

Prevalence and risk factors of chronic kidney disease in the Thai adult population: Thai SEEK study

BACKGROUND Previous reports of chronic kidney disease (CKD) prevalence in Thailand varied from 4.3% to 13.8%. However, there were methodological concerns with these reports in terms of generalization and the accuracy of estimation. This study was, therefore, conducted to determine CKD prevalence and its risk factors in Thai adult populations. METHODS The population-based Thai Screening and Early Evaluation of Kidney Disease (SEEK) study was conducted with cross-sectional stratified-cluster sampling. Serum creatinine was analysed using the modified Jaffe method and then standardized with isotope dilution mass spectrometry. RESULTS The study included 3,459 subjects were included in the study. The mean age was 45.2 years (SE = 0.8), and 54.5% were female. Six hundred and twenty-six subjects were identified as having CKD, which evidenced an overall CKD prevalence of 17.5% [95% confidence interval (95% CI) = 14.6-20.4%]. The CKD prevalence of Stages I, II, III and IV were 3.3% (95% CI = 2.5%, 4.1%), 5.6% (95% CI = 4.2%, 7.0%), 7.5% (95% CI = 6.2%, 8.8%) and 1.1% (95% CI = 0.7%, 1.5%), respectively. The prevalence of CKD was higher in Bangkok, the Northern and Northeastern regions than in the Central and Southern regions. Seven factors (i.e. age, gender, diabetes, hypertension, hyperuricaemia, history of kidney stones and the use of traditional medicines) were associated with CKD. Only 1.9% of the subjects were aware that they had CKD. CONCLUSIONS CKD prevalence in the Thai population is much higher than previously known and published. Early stages of CKD seem to be as common as later stages. However, albuminuria measurement was not confirmed and adjusting for persistent positive rates resulted in the prevalence of 14.4%. Furthermore, the awareness of CKD was quite low in the Thai population.

Personalized Tacrolimus Doses Determined by CYP3A5 Genotype for Induction and Maintenance Phases of Kidney Transplantation

BACKGROUND Cytochrome P450 (CYP) 3A4 and 3A5 are major isoforms involved in the metabolism of tacrolimus, with the CYP3A5 gene being more polymorphic. It is hypothesized that individual variation in the metabolism of tacrolimus drug may result from genetic polymorphism of CYP3A5. It has been reported that the clearance of tacrolimus in patients with the CYP3A5*1 allele was ~2.5-fold greater than that in those with the CYP3A5*3/*3 genotype. Recent data have also shown that polymorphism in exon 26 (C3435T) of the multidrug resistance gene (MDR1) was correlated with the expression level and function of P-glycoprotein in the lower duodenum, making the relationship between polymorphism of MDR1 and the effective dose of tacrolimus a source of controversy. OBJECTIVES This study investigated the influence of genetic polymorphisms of CYP3A5 and MDR1 on the dose requirements for the induction and maintenance phases of tacrolimus therapy in kidney transplant recipients. METHODS Sixty-eight kidney transplant recipients were enrolled, and their clinical and laboratory data were retrospectively reviewed after 6 months of tacrolimus administration. Genotypes of CYP3A5*1 and CYP3A5*3 and exon 26 of MDR1 (C3435T) were determined by the single-nucleotide polymorphism genotyping method. RESULTS The frequencies of CYP3A5*3/*3, CYP3A5*1/*3, and CYP3A5*1/*1 were 44.1%, 35.3%, and 20.6%, respectively. The mean dose of tacrolimus required for the induction phase was significantly greater in the CYP3A5*1/*1 group (0.142 [0.050] mg/kg/d) than that required in the CYP3A5*1/*3 group (0.097 [0.040] mg/kg/d; P = 0.072) and in the CYP3A5*3/*3 group (0.077 [0.020] mg/kg/d; P = 0.005). The maintenance dose of tacrolimus required in the CYP3A5*1/*1 group (0.12 [0.03] mg/kg/d) was 1.3-fold higher than that in the CYP3A5*1/*3 group (0.09 [0.03] mg/kg/d; P = 0.018) and 2.4-fold higher than in the CYP3A5*3/*3 group (0.05 [0.02] mg/kg/d; P < 0.0001). No statistically significant relationship was observed between the doses of tacrolimus required for the induction and maintenance phases and MDR1 polymorphism. CONCLUSION Determination of the CYP3A5 genotype would be helpful in the design of adequate immunosuppressive treatment and in lowering toxicity by predicting the doses of tacrolimus required for the induction and maintenance phases in individual kidney transplant recipients.

Impact of the heterozygous TPMT*1/*3C genotype on azathioprine-induced myelosuppression in kidney transplant recipients in Thailand

BACKGROUND Thiopurine S-methyltransferase (TPMT) is a polymorphic enzyme associated with detoxification of azathioprine, an immunosuppressant used after renal transplantation in several Asian countries. Patients with variations of the TPMT gene may be at risk for myelosuppression after they receive a standard dosage of the drug. The frequency of TPMT*3C has been reported to be higher in the Thai population than in other Asian populations, possibly putting the Thais at higher risk for myelosuppression. OBJECTIVE The aim of this study was to assess the impact of the heterozygous TPMT*1/*3C genotype on azathioprine-induced myelosuppression in kidney transplant recipients in Thailand. METHODS This study was conducted at Srinagarind Hospital, Khon Kaen University, Khon Kaen, Thailand, and Chulalongkorn Hospital, Chulalongkorn University, Bangkok, Thailand. Eligible patients underwent kidney transplantation from deceased or living-related donors from 1984 to 2007. Electronic medical records were assessed retrospectively for the 6-month period after initiation of azathioprine treatment. TPMT genotyping and phenotyping were studied prospectively using real-time polymerase chain reaction and biochemical assay, respectively. The odds ratios (ORs), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined. RESULTS A total of 139 patients were enrolled (89 men, 50 women; median age, 42 years [range, 17-70 years]; mean weight, 58 kg [range, 37-87 kg]). The heterozygous TPMT*1/*3C genotype was found in 9 of the 139 patients (6.47%) (95% CI, 3.00-11.94). The TPMT activity of those patients was significantly lower than that of patients with the homozygous wild-type genotype (median, 21.37 vs 37.12 nmol 6-methylthioguanine/g . Hb/h, respectively; P < 0.001). The risk for azathioprine-induced myelosuppression in the patients with the heterozygous TPMT*1/*3C genotype was significantly higher than that in patients with the wild-type genotype (adjusted OR, 14.18 [95% CI, 3.07-65.40]; P < 0.005). The sensitivity and specificity of TPMT*3C genotyping for the prediction of azathioprine-induced myelosuppression in these kidney transplant recipients were 27% and 97%, respectively. Assuming a prevalence of azathioprine-induced myelotoxicity of 7% according to previously published data, the PPV and NPV were estimated to be 50% and 95%, respectively. CONCLUSION In these kidney transplant recipients, patients who carried the TPMT*3C allele were at a higher risk for azathioprine-induced myelosuppression than noncarriers.

Dialysis dose and risk factors for death among ESRD patients treated with twice-weekly hemodialysis: a prospective cohort study.

Background/Aims: We aimed to define the dosing and risk factors for death in patients undergoing twice-weekly hemodialysis. Methods: A prospective multi-center cohort study was conducted with one-year observation. Patients treated with twice- or thrice-weekly hemodialysis were identified. Death and first admission were the outcomes. spKt/V was a factor of interest. Results: We enrolled 504 twice-weekly and 169 thrice-weekly hemodialysis patients. The mean weekly values of spKt/V in the two groups were 3.4 and 5.1. The one-year survival rate and times to hospitalization were similar in both groups. The hazard ratios for death in higher spKt/V quartile was not associated with lower mortality, p = 0.70. The four significant predictors for death were serum albumin, HR = 2.6, current smoking, HR = 19.3, age, HR = 1.1, and the Index of Coexistent Disease [ICED], HR = 1.9. Conclusion: The effect of spKt/V on short-term mortality was not obvious in twice-weekly dialysis patients. Attention should be paid to patients who smoke, have hypoalbuminemia, are elderly, or have a high ICED.

Immediate Effects of Traditional Thai Massage on Psychological Stress as Indicated by Salivary Alpha-Amylase Levels in Healthy Persons

Background Stress can cause psychological and physiological changes. Many studies revealed that massage can decrease stress. However, traditional Thai massage has not been well researched in this regard. The purpose of this study was to investigate the immediate effects of traditional Thai massage (TTM) on salivary alpha-amylase levels (sAA), heart rate variability (HRV), autonomic nervous system (ANS) function, and plasma renin activity (PRA). Material/Methods Twenty-nine healthy participants were randomly allocated into either a traditional Thai massage (TTM) group or Control (C) group, after which they were switched to the other group with a 2-week wash-out period. Each of them was given a 10-minute mental arithmetic test to induce psychological stress before a 1-hour session of TTM or rest. Results Within-groups comparison revealed that sAA was significantly decreased (p<0.05) in the TTM group but not in the C group. HRV and ANS function were significantly increased (p<0.05) and PRA was significantly decreased (p<0.05) in both groups. However, low frequency per high frequency ratio (LF/HF ratio) and ANS balance status were not changed. Only sAA was found to be significantly different between groups (p<0.05). Conclusions We conclude that both TTM and rest can reduce psychological stress, as indicated by decreased sAA levels, increased parasympathetic activity, decreased sympathetic activity, and decreased PRA. However, TTM may have a modest effect on stress reduction as indicated by a reduced sAA.

SURVIVAL ANALYSIS AND ASSOCIATED FACTORS IN THAI PATIENTS ON PERITONEAL DIALYSIS UNDER THE PD FIRST POLICY

Background: The peritoneal dialysis First (PD-First) policy means that PD is the first modality of dialysis chosen for patients with end-stage renal disease (ESRD), as put forth by the Universal Health Coverage (UHC) scheme. It was initiated in Thailand in 2008. Our aim is to analyze patient survival, technique survival, and associated factors. Methods: Data of PD patients from January 2008 to November 2016 were studied. We calculated patient and technique survival rates (censored for death and kidney transplantation). Factors associated with survival were analyzed by the Cox proportional hazard model. Patient and technique survival rates between 2008 – 2012 and 2013 – 2016 were compared. Results: Our study included 11,477 patients. The mean (standard deviation [SD]) age at initiation of PD was 54.0 (14.4) years. The level of education in 85.2% of cases was illiterate or primary school. A total of 60.9% of patients developed ESRD secondary to diabetes. The 1- to 5-year patient survival rates were 82.6, 71.8, 64.0, 58.5, and 54.0%, respectively. The first-year technique survival rate was 94.8%. The patient and technique survival rates during 2013 – 2016 were better than those seen during 2008 – 2012. Factors associated with lower patient survival rates were: female gender, increased age at start of PD, coverage with civil servant medical benefit scheme, low educational levels, and a history of diabetes. Conclusion: Most patients had diabetes and low educational levels as seen in the outcomes in the previous literature. These factors impacted the survival of patients under the PD-First policy.