Suchai Sritippayawan

Mahidol University, Bangkok, Bangkok, Thailand

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Publications (18)45.81 Total impact

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    ABSTRACT: Kidney stone disease (KSD) is a complex disorder with unknown etiology in majority of the patients. Genetic and environmental factors may cause the disease. In the present study, we used DNA microarray to genotype single nucleotide polymorphisms (SNP) and performed candidate gene association analysis to determine genetic variations associated with the disease.
    BMC Medical Genetics 05/2014; 15(1):50. · 2.54 Impact Factor
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    ABSTRACT: Colistin, administered intravenously as its inactive prodrug colistin methanesulfonate (CMS), is increasingly used as last-line therapy to combat multidrug-resistant gram-negative bacteria. CMS dosing needs to be adjusted for renal function. The impact of continuous ambulatory peritoneal dialysis (CAPD) on the pharmacokinetics of both CMS and colistin has not been studied. No CMS dosing recommendations are available for patients receiving CAPD.Eight CAPD patients received a single intravenous CMS dose (150 mg colistin base activity (CBA)) over 30 min. Serial blood and dialysate samples were collected over 25 h, and cumulative urine where applicable. CMS and colistin concentrations were determined by high-performance liquid chromatography. Population pharmacokinetic modeling and Monte Carlo simulations were conducted.Total body clearance of CMS (excluding CAPD clearance) was 1.77 L/h (44%) [population mean (between subject variability)], while CAPD clearance was 0.088 L/h (64%). The population mean terminal half-life of CMS was 8.4 h. For colistin, total clearance/fm (excluding CAPD clearance; fm, fraction of CMS metabolized to colistin) was 2.74 L/h (50%), CAPD clearance was 0.101 L/h (34%), and mean terminal half-life 13.2 h. Monte Carlo simulations suggested a loading dose of 300 mg CBA on day 1 and a maintenance dose of either 150 mg or 200 mg CBA daily to achieve a target average steady-state plasma colistin concentration of 2.5 mg/L.Clearance by CAPD was low for both CMS and formed colistin. Therefore CMS doses should not be increased during CAPD. Modeling and simulation enabled proposing of the first evidence-based CMS dosage regimen for CAPD patients.
    Antimicrobial Agents and Chemotherapy 11/2013; · 4.57 Impact Factor
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    ABSTRACT: We previously reported the association between prothrombin (F2), encoding a stone inhibitor protein - urinary prothrombin fragment 1 (UPTF1), and the risk of kidney stone disease in Northeastern Thai patients. To identify specific F2 variation responsible for the kidney stone risk, we conducted sequencing analysis of this gene in a group of the patients with kidney stone disease. Five intronic SNPs (rs2070850, rs2070852, rs1799867, rs2282687, and rs3136516) and one exonic non-synonymous single nucleotide polymorphism (nsSNP; rs5896) were found. The five intronic SNPs have no functional change as predicted by computer programs while the nsSNP rs5896 (c.494 C>T) located in exon 6 results in a substitution of threonine (T) by methionine (M) at the position 165 (T165M). The nsSNP rs5896 was subsequently genotyped in 209 patients and 216 control subjects. Genotypic and allelic frequencies of this nsSNP were analyzed for their association with kidney stone disease. The frequency of CC genotype of rs5896 was significantly lower in the patient group (13.4%) than that in the control group (22.2%) (P = 0.017, OR 0.54, 95% CI 0.32-0.90), and the frequency of C allele was significantly lower in the patient group (36.1%) than that in the control group (45.6%) (P = 0.005, OR 0.68, 95% CI 0.51-0.89). The significant differences of genotype and allele frequencies were maintained only in the female group (P = 0.033 and 0.003, respectively). The effect of amino-acid change on UPTF1 structure was also examined by homologous modeling and in silico mutagenesis. T165 is conserved and T165M substitution will affect hydrogen bond formation with E180. In conclusion, our results indicate that prothrombin variant (T165M) is associated with kidney stone risk in the Northeastern Thai female patients.
    PLoS ONE 01/2012; 7(9):e45533. · 3.53 Impact Factor
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    ABSTRACT: Background: Emergence of multidrug-resistant (MDR) gram-negative bacteria (GNB) has led to resurgence of colistin for therapy of MDR GNB infections. Data on PK of CMS and colistin, and appropriate dosage regimens of CMS for ESRD patients receiving chronic HD are limited. The aim of the study was to determine PK of CMS and colistin in ESRD patients receiving chronic HD. Methods: 10 ESRD patients (8 male, median age 54 y, and median body weight 71 Kg) receiving adequate regular 4-h HD session 3 times a week were enrolled. A single dose of CMS (150 mg colistin base activity, CBA) was infused IV over 30 min. Serial blood samples from peripheral vein (pre and 0.5, 1, 2, 4, 6, 8, 12, 24 and 48 h post-start CMS infusion) were collected. HD was commenced 1 h after CMS infusion. Serial blood samples from arterial side and venous side of HD catheter were collected at 0.5, 1.5 and 2.5 h after commencing HD. Hemodialysate samples were collected at 0.5, 1.5, 2.5 and 3.5 h after commencing HD. 24-h urine samples were also collected. CMS and colistin concentrations in plasma, hemodialysate and urine were quantified by HPLC. PK analysis was conducted using WinNonlin. Results: Two-compartmental model was fitted for CMS PK in plasma (R2=0.98), and one-compartmental model for colistin PK in plasma (R2=0.94). The mean (SD) predicted PK parameters and AUC0-24 of CMS and colistin in plasma are shown below. Appar Vd (L) Appar CL (L/h) Cmax (mg/L) Tmax (h) T1/2 (h) AUC0-24 (h.mg/L) CMS 43.3 (27.0 ) 5.4 (0.4) 29.8 (21.0) -- 11.3 (5.9) 79.0 (11.5) Colistin 183.0 (62.0) 4.4 (1.2) 0.7 (0.2) 8.3 (3.1) 31.6 (8.6) 14.8 (3.3) Conclusion: Colistin clearance in ESRD patients receiving chronic HD was high resulting in low plasma colistin concentrations for entire 24 h and small AUC0-24 after administration of 150 mg CBA. The predicted PK parameters are useful for determining CMS dosage regimen if the ESRD patients receiving chronic HD require CMS therapy.
    Infectious Diseases Society of America 2011 Annual Meeting; 10/2011
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    ABSTRACT: Implementation of the "Peritoneal Dialysis-First (PD First)" policy, mandating PD as the first modality of renal replacement therapy for end-stage renal disease patients under universal health coverage, leads to a rapid growth of PD cases and centers in Thailand. Since PD-related infection is the Achilles' heel of PD, this retrospective study was conducted to examine the magnitude of PD-related infection in Thailand under the "PD First" policy. All PD centers in Thailand were included in the present study. PD nurse specialists in each center were requested to review medical records of all patients undergoing PD during October 1, 2009 to September 30, 2010 and to submit data to the main investigators. Eighty-eight percent of all active PD-centers in Thailand (102 out of 116) participated in the present study. One hundred and thirty-three nephrologists and 220 PD nurse specialists served 8,201 PD prevalent patients in these centers (7,925 CAPD and 276 APD). The overall exit-site infection (ESI) rate was 1 episode/37.7 patient-month (0.32 episodes/patient-year) while the overall peritonitis rate was 1 episode/25.5 patient-month (0.47 episode/patient-year). Despite the rapid growth of PD cases under the limited resource, the PD-related infection rates in Thailand are only small degree behind the goal of Asia-Pacific Key Performance Indicators (KPIs) Task Force.
    Journal of the Medical Association of Thailand = Chotmaihet thangphaet 09/2011; 94 Suppl 4:S7-12.
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    ABSTRACT: The development of APD technologies enables physician to customize PD treatment for optimal dialysis. Dialysis dose can be increased with APD alone or in conjunction with daytime dwells. Although there is no strong evidence of the advantage over CAPD, APD is generally recommended for patients having a high peritoneal transport, outflow problems or high intraperitoneal pressure (IPP) and those who depend on caregivers for their dialysis. The benefits of APD over CAPD depends on the problems and treatment results among dialysis centers. Before starting the APD, medical, psychosocial and financial aspects, catheter function, residual renal function (RRF), body surface area and peritoneal transport characteristic must be evaluated. The recommended starting prescription for APD is the dwell volume of 1,500 ml/m2, 2 hours/cycle, and 5 cycles/session, which will provides 10-15 L of total volume and 10 hours per session. The IPP should be monitored and kept below 18 cmH2O. NIPD is accepted for patients with significant RRF. Anuric patients usually require 15-20 L of total fill volume and may need 1-2 day-dwells of 2L icodextrin or hypertonic glucose solutions. Small solute clearances and ultrafiltration depend on the peritoneal catheter function and dialysis schedule. The clinical outcomes and small solute clearances must be monitored and adjusted accordingly to meet the weekly total Kt/V urea > or = 1.7 and in low peritoneal transporters, the weekly total CCr should be > or = 45 L/1.73 m2. The volume status must be normal. To diagnose the peritonitis in NIPD patients, 1 L of PDF should be infused and permitted to dwell for 2 hours before sending for analysis. The differential of white cell count may be more useful than the total cell counts. In Siriraj Hospital, APD patients had 1.5-3 times less peritonitis than CAPD patients and most of our anuric patients can achieve the weekly total Kt/V urea target with 10 L of NIPD.
    Journal of the Medical Association of Thailand = Chotmaihet thangphaet 09/2011; 94 Suppl 4:S167-74.
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    ABSTRACT: To evaluate genetic variations associated with kidney stone disease in Northeastern Thai patients. Altogether, 67 single nucleotide polymorphisms (SNP) distributed within 8 candidate genes, namely TFF1, S100A8, S100A9, S100A12, AMBP, SPP1, UMOD, and F2, which encode stone inhibitor proteins, including trefoil factor 1, calgranulin (A, B, and C), bikunin, osteopontin, tamm-Horsfall protein, and prothrombin, respectively, were initially genotyped in 112 individuals each and in additional subjects to consist of 164 patients and 216 control subjects in total. We found that minor allele and homozygous genotype frequencies of 8 of 10 SNPs distributed within the F2 gene were significantly higher in the control group than in the patient group. Two F2 haplotypes were found to be dually associated with kidney stone risk, one (TGCCGCCGCG) with increased disease risk and the other (CGTTCCGCTA) with decreased disease risk. However, these 2 haplotypes were associated with the disease risks in only the female, not the male, group. The results of our study indicate that genetic variation of F2 is associated with kidney stone risk in Northeastern Thai female patients.
    Urology 11/2010; 77(1):249.e17-23. · 2.42 Impact Factor
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    ABSTRACT: With 37-years of experience, a total of 801 kidney transplantations (59.4% were deceased donors and 40.6% were living donors) performed at Siriraj hospital were reported. The point system parallel to OPTN/UNOS for waitlists was utilized. Most of the recipients of deceased donor kidney transplantations had 3 HLA mismatches. Due to the point allocation system, none of them had 6 HLA mismatches. Extended criteria donor comprised 7.8% of all deceased donors. Mean duration of dialysis prior to deceased donor transplant was 53 +/- 34 months. Delayed graft function (DGF) was found in 54% of deceased donor kidney transplantation and resulted in significantly higher rate of 1 year biopsy-proven acute rejection, longer duration of kidney transplant admission, higher admission cost and lower patient survival compared to those with immediate graft function. Most of living donor kidney transplant recipient had 1 haplotype match. Mean donor age was 35.9 +/- 9.8 years. 95.6% of the recipients were on hemodialysis prior to transplantation. The current standard regimen includes calcineurin inhibitor, Mycophenolic acid and prednisolone. Interleukin-2 receptor monoclonal antibody has been used in the high immunological risk or high risk for DGF recipients that were 50% of the recipients. There was no statistically significant difference in the biopsy-proven acute rejection (BPAR) free survival between deceased and living donor transplantation. Proportion of cases with the diagnosis of acute rejection according to Banff 2007 classification is as follows: 32.4% acute cellular rejection (ACR), 39.4% antibody-mediated rejection (AMR) and 21.1% mixed cellular and antibody-mediated rejection. Seventy two patients, 35 deceased donor and 37 living donor kidney transplant recipients, had biopsy-proven glomerular disease after transplantation which IgA nephropathy is the most common form of glomerulonephritis. Median graft survival was 7.6 and 13.2 years and median patient survival was 12.1 and 15.5 years for recipient of deceased and living donor transplant respectively. The follow up program of living donors was introduced in 2003 and there were not any donors who required renal replacement therapy.
    Clinical transplants 01/2010;
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    ABSTRACT: Assess the reliability and validity of the Thai translation of the CHOICE Health Experience Questionnaire (CHEQ), which is the English-language questionnaire, developed specifically for End-stage-renal disease (ESRD) patients. The CHEQ comprised of two parts, nine general domains of SF-36 (physical function, role-physical, bodily pain, mental health, role-emotional, social function, vitality, general health, and report transition) and 16 dialysis specific domains of the CHEQ (role-physical, mental health, general health, freedom, travel restriction, cognitive function, financial function, restriction diet and fluids, recreation, work, body image, symptoms, sex, sleep, access, and quality of life). The authors translated the CHEQ questionnaire into Thai and confirmed the accuracy by back translation. Pilot study sample was 10 Thai ESRD patients. Then the CHEQ (Thai) was applied to 110 Thai ESRD patients. Twenty-three patients had chronic peritoneal dialysis patients and 87 were chronic intermittent hemodialysis patients. Statistical analysis included descriptive statistics, Mann-Whitney U test, Student's t-test, and Cronbach's alpha. Construct validity was satisfactory with the significant difference less than 0.001 between the low and high group. The reliability coefficient for the Cronbach's alpha of the total scale of the CHEQ (Thai) was 0.98. The Cronbach 's alphas were greater than 0.7 for all domains, range from 0.58 to 0.92, except the social function and quality of life domain (alpha = 0.66 and 0.575). The CHEQ (Thai) is reliable and valid for assessment of Thai ESRD patients receiving chronic dialysis. Its properties are similar to those reported in the original version.
    Journal of the Medical Association of Thailand = Chotmaihet thangphaet 09/2009; 92(9):1159-66.
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    ABSTRACT: Genetic factor may play a role in the pathogenesis of kidney stone that is found in the northeastern (NE) Thai population. Herein, we report initial evidence suggesting genetic contribution to the disease in this population. We examined 1,034 subjects including 135 patients with kidney stone, 551 family members, and 348 villagers by radiography of kidney-ureter-bladder (KUB) and other methods, and also analyzed stones removed by surgical operations. One hundred and sixteen of 551 family members (21.05%) and 23 of the 348 villagers (6.61%) were affected with kidney stone. The relative risk (lambda(R)) of the disease among family members was 3.18. Calcium stones (whewellite, dahllite, and weddellite) were observed in about 88% of stones analyzed. Our data indicate familial aggregation of kidney stone in this population supporting that genetic factor should play some role in its pathogenesis. Genetic and genomic studies will be conducted to identify the genes associated with the disease.
    Urological Research 05/2009; 37(3):141-6. · 1.59 Impact Factor
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    ABSTRACT: Efficacy of peritoneal dialysis is determined by solute transport through peritoneal membranes. With the use of the peritoneal equilibration test (PET), peritoneal membranes can be classified as high (H), high average (HA), low average (LA), and low (L) transporters, based on the removal or transport rate of solutes, which are small molecules. Whether there is any difference in macromolecules (i.e., proteins) removed by different types of peritoneal membranes remains unclear. We performed a gel-based differential proteomics study of peritoneal dialysate effluents (PDE) obtained from chronic peritoneal dialysis (CPD) patients with H, HA, LA, and L transport rates (n=5 for each group; total n=20). Quantitative analysis and ANOVA with Tukey's posthoc multiple comparisons revealed five proteins whose abundance in PDE significantly differed among groups. These proteins were successfully identified by matrix-assisted laser desorption ionization quadrupole time-of-flight (MALDI-Q-TOF) mass spectrometry (MS) and tandem mass spectrometry (MS/MS) analyses, including serum albumin in a complex with myristic acid and triiodobenzoic acid, alpha1-antitrypsin, complement component C4A, immunoglobulin kappa light chain, and apolipoprotein A-I. The differences among groups in PDE levels of C4A and immunoglobulin kappa were clearly confirmed in a validation set of the other 24 patients (n=6 for each group) using ELISA. These data may lead to better understanding of the physiology of peritoneal membrane transport in CPD patients. Extending the study to a larger number of patients with subgroup analyses may yield additional information of the peritoneal dialysate proteins in association with dialysis adequacy, residual renal function, nutritional status, and risk of peritoneal infection.
    Journal of Proteome Research 12/2007; 6(11):4356-62. · 5.06 Impact Factor
  • Visith Thongboonkerd, Napat Songtawee, Suchai Sritippayawan
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    ABSTRACT: Clinical diagnostics and biomarker discovery are the major focuses of current clinical proteomics. In the present study, we applied microfluidic technology on a chip for proteome profiling of human urine from 31 normal healthy individuals (15 males and 16 females), 6 patients with diabetic nephropathy (DN), and 4 patients with IgA nephropathy (IgAN). Using only 4 microL of untreated urine, automated separation of proteins/peptides was achieved, and 1-7 (3.8 +/- 0.3) spectra/bands of urinary proteins/peptides were observed in the normal urine, whereas 8-16 (11.3 +/- 1.2) and 9-14 (10.8 +/- 1.2) spectra were observed in urine samples of DN and IgAN, respectively. Coefficient of variations of amplitudes of lower marker (1.2 kDa), system spectra (6-8 kDa), and upper marker (260.0 kDa) were 22.84, 24.92, and 32.65%, respectively. ANOVA with Tukey post-hoc multiple comparisons revealed 9 spectra of which amplitudes significantly differed between normal and DN urine (DN/normal amplitude ratios ranged from 2.9 to 3102.7). Moreover, the results also showed that 3 spectra (with molecular masses of 12-15, 27-28, and 34-35 kDa) were significantly different between DN and IgAN urine (DN/IgAN amplitude ratios ranged from 3.9 to 7.4). In addition to the spectral amplitudes, frequencies of some spectra could differentiate the normal from the diseased urine but could not distinguish between DN and IgAN. There was no significant difference, regarding the spectral amplitude or frequency, observed between males and females. These data indicate that the microfluidic chip technology is applicable for urinary proteome profiling with potential uses in clinical diagnostics and biomarker discovery.
    Journal of Proteome Research 06/2007; 6(5):2011-8. · 5.06 Impact Factor
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    ABSTRACT: 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. To identify the prevalence of primary and secondary glomerular diseases and to study the trend of the pattern changes of the glomerulopathy in Thailand. 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. 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. 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.
    Journal of the Medical Association of Thailand = Chotmaihet thangphaet 09/2006; 89 Suppl 2:S106-11.
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    ABSTRACT: 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. 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. 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). 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.
    Journal of the Medical Association of Thailand = Chotmaihet thangphaet 09/2006; 89(8):1187-93.
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    ABSTRACT: Previous research on proteins that inhibit kidney stone formation has identified a relatively small number of well-characterized inhibitors. Identification of additional stone inhibitors would increase understanding of the pathogenesis and pathophysiology of nephrolithiasis. We have combined conventional biochemical methods with recent advances in mass spectrometry (MS) to identify a novel calcium oxalate (CaOx) crystal growth inhibitor in normal human urine. Anionic proteins were isolated by DEAE adsorption and separated by HiLoad 16/60 Superdex 75 gel filtration. A fraction with potent inhibitory activity against CaOx crystal growth was isolated and purified by anion exchange chromatography. The protein in 2 subfractions that retained inhibitory activity was identified by matrix-assisted laser desorption/ionization-time-of-flight MS and electrospray ionization-quadrupole-time-of-flight tandem MS as human trefoil factor 1 (TFF1). Western blot analysis confirmed the mass spectrometric protein identification. Functional studies of urinary TFF1 demonstrated that its inhibitory potency was similar to that of nephrocalcin. The inhibitory activity of urinary TFF1 was dose dependent and was inhibited by TFF1 antisera. Anti-C-terminal antibody was particularly effective, consistent with our proposed model in which the 4 C-terminal glutamic residues of TFF1 interact with calcium ions to prevent CaOx crystal growth. Concentrations and relative amounts of TFF1 in the urine of patients with idiopathic CaOx kidney stone were significantly less (2.5-fold for the concentrations and 5- to 22-fold for the relative amounts) than those found in controls. These data indicate that TFF1 is a novel potent CaOx crystal growth inhibitor with a potential pathophysiological role in nephrolithiasis.
    Journal of Clinical Investigation 01/2006; 115(12):3613-22. · 12.81 Impact Factor
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    ABSTRACT: 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. 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 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. 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.
    Journal of the Medical Association of Thailand = Chotmaihet thangphaet 10/2005; 88(10):1373-81.
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    ABSTRACT: Mutations in the SLC4A1 gene have been found to cause either autosomal dominant (AD) or autosomal recessive (AR) distal renal tubular acidosis (dRTA). The SLC4A1 mutations causing AD dRTA were reported in white patients, whereas those associated with AR dRTA were often found in Southeast Asia. Here, the authors report additional novel SLC4A1 mutations in 3 patients with AR dRTA from 2 unrelated Thai families. The patients and members of their families were clinically studied. Red cell morphology and sulfate influx were examined. The SLC4A1 gene was screened, analyzed, and confirmed for mutations by molecular genetic techniques. In the first family, the patient had dRTA, rickets, failure to thrive, nephrocalcinosis, and hypokalemic-hyperchloremic metabolic acidosis with a urine pH level of 7.00. He had novel compound heterozygous SLC4A1 G701D/S773P mutations, inherited from clinically normal heterozygous mother and father. In the second family, the patient and his sister had dRTA and Southeast Asian ovalocytosis (SAO) with different clinical severity. The patient had proximal muscle weakness, rickets, nephrocalcinosis, hypokalemia, normal anion gap metabolic acidosis, and urine pH level of 6.80. His sister was asymptomatic but the urine pH level could not be lowered to below 5.50 after a short acid load. Both siblings had compound heterozygous SLC4A1 SAO/R602H mutations. Two novel compound heterozygous SLC4A1 G701D/S773P and SAO/R602H mutations were identified in Thai patients with AR dRTA.
    American Journal of Kidney Diseases 08/2004; 44(1):64-70. · 5.29 Impact Factor
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    ABSTRACT: Anion exchanger 1 (AE1 or SLC4A1) mutations have been reported to cause distal renal tubular acidosis (dRTA), a disease characterized by impaired acid excretion in the distal nephron. We have recently demonstrated homozygous AE1 G701D mutation as a common molecular defect of autosomal recessive (AR) dRTA in a group of Thai pediatric patients. In the present work, we discovered a de novo heterozygous AE1 R589C mutation, previously documented in inherited autosomal dominant (AD) dRTA. Arginine at this position is conserved in all vertebrate AE proteins indicating its functional importance. Three different mutations at this position (R589C, R589H, and R589S) were all found in AD dRTA and a de novo R589H mutation has previously been recorded. Our report is the second de novo mutation but with a different substituted amino acid. A high prevalence of AE1 R589 mutations and the presence of at least two de novo mutations at this position lead us to propose that codon 589 (CGC) is a "mutational hotspot" of AE1. The mechanism of recurrent mutations probably involves methylation and deamination altering cytosine (C) to thymine (T) in the CpG dinucleotides.
    Pediatric Nephrology 08/2003; 18(7):644-8. · 2.94 Impact Factor