Surasak Kantachuvesiri

Mahidol University, Siayuthia, Bangkok, Thailand

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Publications (33)100.51 Total impact

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    ABSTRACT: Purpose: The purpose of this study is to determine the impacts of CYP3A5 polymorphism on tacrolimus concentration and the proportion of patients within a target therapeutic range during the first week after transplantation together with the 3-month acute rejection rate in kidney transplant patients receiving a minimized tacrolimus regimen. Methods: A total of 164 patients participated in the study. All received oral tacrolimus twice daily starting on the day of surgery with the target pre-dose (trough) concentration of 4-8 ng/ml for prevention of allograft rejection. Cytochrome P450 (CYP) 3A5 genotypes were determined. The patients were divided into CYP3A5 expressers (CYP3A5*1 allele carriers) and CYP3A5 nonexpressers (homozygous CYP3A5*3). Whole blood tacrolimus concentrations on days 3 and 7 posttransplantation and the incidence of biopsy-proven acute rejection (BPAR) at 3-month posttransplantation were compared between groups. Results: On day 3, the median (IQR) dose-and-weight-normalized trough concentration in expressers and nonexpressers were 54.61 (31.98, 78.87) and 91.80 (57.60, 130.20) ng/ml per mg/kg/day, respectively (p < 0.001). Although only 47 and 42 % of expressers and nonexpressers were within the target range on day 3, approximately 60 % of both groups were within the target range on day 7. Proportions of BPAR among expressers and nonexpressers were 6.0 and 7.4 %, respectively (p = 0.723). The median (IQR) times to the first rejection in CYP3A5 expressers and nonexpressers were 32 (12, 68) and 15 (12, 37) days, respectively (p = 0.410). Conclusions: Although CYP3A5 polymorphism significantly influenced the tacrolimus dose required to achieve the target concentration, the impact of CYP3A5 polymorphism on BPAR was not observed in this study.
    No preview · Article · Dec 2015 · European Journal of Clinical Pharmacology
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    ABSTRACT: Human leukocyte antigen (HLA)-G is a nonclassical HLA class I molecule that displays strong immune-inhibitory properties and has been associated with allograft acceptance. However, there are conflicting data on the correlation of soluble HLA-G (sHLA-G) and acute rejection and no data on the correlation with acute tubular necrosis in kidney transplantation. To evaluate the association of sHLA-G level in early post-transplant period and allograft rejection/ and acute tubular necrosis (ATN) in kidney transplant recipients. The sera procured before transplantation and serially on day 3 and day 7 after transplantation from 76 kidney transplant recipients were analyzed for the level of sHLA-G by enzyme-linked immunosorbent assay. The levels of sHLA-G from three serial sera did not differ between patients with acute rejection and patients without rejection. However, the sHLA-G levels on day 3 post-transplant and day 7 post-transplant in patients with ATN were significantly higher than that in patients without ATN (16.3 vs 9.85 U/ml, p = 0.018, for day 3 post-transplant and 12.47 vs 5.42 U/ml, p = 0.044, for day 7 post-transplant). In addition, the ROC analysis of sHLA-G for identifying patients with ATN showed that the area under curve was 0.67 (95% confidence interval 0.54-0.80). There was no significant difference for sHLA-G levels between patients with acute rejection and without rejection. Interestingly, high levels of sHLA-G in day 3 and day 7 after transplantation were associated with acute tubular necrosis. Our findings raise the question whether the increased levels of sHLA-G in patients with acute tubular necrosis after transplantation might be a result of ischemia and reperfusion injury.
    No preview · Article · Jun 2015 · Asian Pacific journal of allergy and immunology / launched by the Allergy and Immunology Society of Thailand
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    ABSTRACT: Context .- The deposition of extracellular matrix is a major pathogenic mechanism leading to fibrosis and progressive decline in renal function in patients with lupus nephritis (LN). Currently, available clinicopathologic features cannot predict renal outcome consistently. Objective .- To test that the expression of renal fibrogenic genes correlates with renal fibrosis at the time of biopsy and is predictive of renal outcomes. Design .- Renal gene expression levels of transforming growth factor β-1 (TGFB1), and collagen I (COL1) were studied by real-time multiplex quantitative polymerase chain reaction in a prospective cohort of patients with LN (n = 39). Extracellular matrix index (ECMI) and collagen I/III matrix index were measured from Picro-Sirius Red-stained slides under normal and polarized light, respectively. Results .- After follow-up (median, 43.9 months), renal failure (50% reduction in glomerular filtration rate [GFR] or dialysis) had developed in 13 subjects. The expression levels of renal fibrogenic genes were increased as compared to controls without LN. COL1 correlated with collagen I/III matrix index at baseline. Both high expression of TGFB1 or COL1 tended to predict renal failure by univariate analysis. By multivariate analysis, high ECMI and low GFR were predictive of renal failure. In patients with baseline GFR of 60 mL/min/1.73 m(2) or greater, high renal COL1 expression was an independent (hazard ratio = 4.4, P = .04) predictor of renal failure. Conclusions .- High renal COL1 expression is a strong predictor of adverse renal outcome in patients with LN and preserved baseline GFR. These findings support larger prospective studies to confirm the benefits of COL1 in identifying patients at high risk of progression to renal disease.
    Full-text · Article · Mar 2015 · Archives of pathology & laboratory medicine
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    ABSTRACT: Background. The renin-angiotensin system (RAS) and transforming growth factor beta(1) (TGF-beta(1)) may play a role in the pathogenesis of fibrosis in kidney allografts. Experimental hyperuricemia shows activation of intrarenal RAS. However, the association between uric acid (UA), RAS, and TGF-beta(1) in allograft recipients has not been demonstrated. Therefore we investigated the association between serum UA levels, RAS, and TGF-beta(1) in kidney transplant recipients during the 1st year after transplantation. Methods. Sixty-two transplant recipients were included in the study. Serum UA level, plasma renin activity (PRA), and urine TGF-beta(1) concentration were studied at 3, 6, and 12 months after transplantation. Statistical correlation was demonstrated with the use of Spearman rank correlation coefficient. Receiver operating characteristic curve analysis and area under the curve were performed to assess the diagnostic performance to discriminate between estimated glomerular filtration rate (eGFR) <60 and >= 60 mL/min/1.73 m(2). Results. For all 62 patients, urine TGF-beta(1) and serum UA had a tendency to increase during the 1-year follow-up period, despite no statistically significant change in eGFR. We found that increased urine TGF-beta(1) was correlated with rising serum UA levels and a decrease of the eGFR (r = 0.27 [P =.01]; r = -0.38 [P =.0003]). In contrast, there was no significant change in PRA and it was not correlated with eGFR or TGF-beta(1) (r = -0.01; P =.93). Conclusions. Increased urine TGF-beta(1) and serum UA level during the 1st year after transplantation correlated with a decline in eGFR. The evaluation of these parameters in the early post-transplantation period may identify patients at risk of allograft dysfunction.
    No preview · Article · Mar 2015 · Transplantation Proceedings
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    ABSTRACT: We report a case of propylthiouracil (PTU)-induced double antineutrophil cytoplasmic antibody (ANCA) and anti-glomerular basement membrane antibody (anti-GBM antibody) disease causing pulmonary-renal syndrome in a 35-year-old Thai woman with 10-year history of PTU treatment for thyrotoxicosis. She developed clinical symptoms of vasculitis upon receiving long-term PTU treatment. Prednisolone treatment and the switching from PTU to methimazole resulted to short-term clinical improvement. Nevertheless following termination of steroid treatment, she developed recurrent pulmonary hemorrhage and rapidly progressive glomerulonephritis. The kidney biopsy showed crescentic glomerulonephritis with linear IgG deposit on the glomerular basement membrane although transbronchial lung biopsy showed no immune deposit along the alveolar basement membrane. Serum testing for p-ANCA was positive and western blot showed positive antibody to the alpha-3 chain of collagen type IV. Both ANCA and anti-GBM antibody may play a role in the development of end organ damage. To facilitate early and specific intervention, clinicians should be aware of the propensity of PTU to cause lupus-like syndromes with renal involvement. In patients with PTU-induced ANCA-associated glomerulonephritis, serum anti-GBM antibody test may be useful in the early diagnosis of double positive antibodies disease and plasmapheresis should be performed without delay.
    No preview · Article · Dec 2014

  • No preview · Article · Oct 2014 · Pathology
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    ABSTRACT: Objectives De novo donor-specific HLA antibodies (DSA) are associated with allograft rejection and allograft loss. However, not all DSA are equally detrimental to allograft function. The ability to activate complement may be an important factor differentiating clinically relevant DSA from nonrelevant DSA. The C1q assay detects a subset of HLA antibodies that can fix complement. This study aimed to investigate the correlation between C1q-fixing de novo DSA (dnDSA) and clinical outcomes posttransplant. Methods This retrospective study included 193 sera from kidney transplant recipients who underwent posttransplant DSA testing and/or kidney biopsy for clinical causes. Thirty-five of the 193 (18.1%) had immunoglobulin G DSA. Seventeen of the 35 patients were excluded owing to the presence of pretransplant HLA antibodies. We then analyzed C1q DSA at the time of biopsy in 18 recipients who developed dnDSA. The clinical outcomes of patients with C1q-positive DSA and C1q-negative DSA were compared. Results C1q-positive DSA were detected in 10 of 18 patients (55.6%). The incidences of transplant glomerulopathy were significantly higher among patients with C1q-positive DSA than patients with C1q-negative DSA (80% vs 0%; P = .001). Although patients with C1q-positive DSA experienced more chronic antibody-mediated rejection and graft loss (80% vs 37.5% [P = .145]; 60% vs 25% [P = .188]), the differences were not significant. The receiver operating characteristic curve analysis showed that the C1q assay was an excellent predictor of transplant glomerulopathy with area under the curve of 0.9 (95% CI, 0.769–1.000). Conclusion The presence of C1q-positive dnDSA was associated with an increased risk of transplant glomerulopathy. The C1q assay is potentially a powerful method for identifying patients at risk for transplant glomerulopathy.
    Full-text · Article · Mar 2014 · Transplantation Proceedings
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    ABSTRACT: Background: Bone loss is common among hemodialysis patients and contributes to mortality. The association between bone loss and vascular calcification may explain the increased mortality risk. Studies on the association between decreased bone mass and mortality in maintenance hemodialysis patients are limited. Methods: Eighty-three hemodialysis patients underwent bone mineral density (BMD) and coronary artery calcification (CAC) measurements. The relationship between BMD and mortality was analyzed after a 5-year follow-up period. Results: Eighty percent of the patients had reduced hip BMD. In univariate Cox regression analyses, age, cardiovascular disease, dyslipidemia, increased CAC score, increased comorbidity score and decreased hip BMD were associated with mortality. Low hip BMD remained independently associated with mortality after adjustments for cardiovascular risk factors, comorbidity score and CAC score. Patients with BMD in the lowest tertile had the worst survival. Conclusion: Low hip BMD predicted mortality in maintenance hemodialysis patients independent of CAC.
    No preview · Article · Feb 2014 · Blood Purification
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    ABSTRACT: Vascular calcification (VC) is common among patients with chronic kidney disease (CKD) due to the strong prevalence of cardiovascular and CKD-related risk factors such as DM, hypertension and phosphate retention. Kidney transplantation improves kidney function and abnormal mineral metabolism at the same time. It remains unclear whether kidney transplantation favourably impacts VC in long-term. The present study examined VC in 132 kidney transplant (KT) recipients who had been transplanted for longer than 1 year. The severity of VC was compared to 129 CKD stages 5-5D patients on KT waiting list. The median KT vintage was 88 months. The prevalence of VC among KT and CKD patients were 54.5% and 62.8% respectively (P=0.2). There were no differences in age, gender, BMI, the prevalence of DM or CVD between the 2 groups. Among patients with calcification, a more severe degree was observed in KT recipients (P=0.01). Aging, DM, CVD and dialysis vintage were associated with significant VC in both groups. The degree of VC in KT recipients was more pronounced than that in CKD patients among those who experienced prolonged dialysis vintage (> 2 years) (P=0.04). Among KT recipients, the severity of VC increased with the length of time after transplantation and became more substantial after 5 years. Long-term KT recipients demonstrated a more severe degree of VC compared to matched CKD stages 5-5D patients. The severity of VC became more pronounced among those with longer transplant vintage and was in part influenced by past dialysis experience.
    Full-text · Article · Jan 2014 · Nephrology
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    ABSTRACT: Introduction: Kidney retransplantation is a high-risk procedure that is increasingly performed because of previous graft failure. The aim of this study was to determine the long-term outcomes of kidney retransplantations compared with first kidney transplantations under the current era of immunosuppression. Methods: Since the first retransplantation in Thailand was performed in 1993, this study included all consecutive cases registered in the Thai Transplantation Registry database from January 1993 to December 2011. A total of 3337 kidney transplantations were available for the analysis. Graft loss was defined as a return to dialysis or graft removal. Death with a functioning graft was censored. Results: Of 3337 kidney transplantations during the study period, 113 were second and 3 were third transplantations. Among these 116 retransplantations, the most common identified causes of end-stage renal disease were chronic glomerulonephritis (38.8%), followed by hypertensive nephropathy (13.0%), diabetic nephropathy (6.0%), and lupus nephritis (1.7%). The retransplantation recipients were older (mean age, 46.2 ± 12.8 years) than the first transplantation group (mean age, 42.2 ± 12.8 years). The proportion of living-related kidney transplantations and male sex were similar between first and retransplantation recipients. Fourteen percent of retransplantation recipients showed high immunologic risk as defined by current panel reactive antibodies ≥30% compared with 3% of those in the first transplantation group (P < .001). The percentages of induction therapy with antithymocyte globulin and anti-interleukin-2 antibody in the retransplantation and first transplantation groups were 18.3% versus 4.3% and 60.0% versus 32.6%, respectively. The graft survival rates (95% confidence interval [CI]) at 1, 5, and 10 years were 88.6% (80.7-93.3), 87.3% (79.1-92.5), and 74.4% (53.7-86.9) among retransplantation, versus 95.0% (94.1-95.7), 87.0% (85.5-88.5), and 70.7% (67.4-73.8) among first transplantation groups, respectively (P = .63). Patient survival rates were not different between first and retransplantation groups (P = .42). The leading cause of graft loss in the retransplantation group was chronic allograft nephropathy (22%), whereas infection (57%) was the major cause of death in this group. Conclusion: The 10-year patient and graft survival rates of kidney retransplantation were acceptable. The combination of induction therapy with a calcineurin inhibitor and a mycophenolate mofetil/mychophenolic acid-based regimen lead to outcomes comparable to first kidney transplantations among our cohort of 3337 patients.
    No preview · Article · May 2013 · Transplantation Proceedings
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    ABSTRACT: In lupus nephritis (LN), kidney inflammation may be followed by fibrosis and progressive decline in function. Transforming growth factor (TGF)-β is a notable mediator of fibrosis, but it has other beneficial roles, thus indicating a need for alternate therapeutic targets for inhibition of fibrosis. Connective tissue growth factor (CTGF) acts as a downstream mediator of TGF-β in promoting fibrosis, without mediating the immunosuppressive effects of TGF-β. Animal studies show that CTGF may have important roles in renal fibrosis, but data are limited in human subjects. The present study tested the hypothesis that renal CTGF mRNA expression is related to TGF-β1 and collagen I expression and is predictive of renal function deterioration in patients with LN (n=39). Gene expression was measured using multiplex real-time quantitative RT-PCR and renal function was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) glomerular filtration rate (GFR) equation. Decline in GFR was assessed by regression of GFR at biopsy to 1 year following biopsy. CTGF mRNA expression was significantly correlated with TGF-β1 and collagen I. GFR at biopsy was 89.2±39.2 ml/ min. Renal CTGF mRNA expression correlated inversely with baseline GFR. Renal CTGF mRNA was significantly higher in patients with moderate to severe CKD compared to those in the milder CKD group (low GFR 4.92±4.34 vs. high GFR 1.52±1.94, p<0.005). CTGF mRNA was also higher in patients with subsequent decline in GFR [GFR decline (5.19±4.46) vs. no GFR decline (1.79±1.97); P<0.01]. In conclusion, renal expression of CTGF was positively related to TGF-β1 and collagen I in patients with LN. Furthermore, high CTGF mRNA expression was associated with poor GFR at baseline and subsequent deterioration of kidney function. CTGF expression in the kidney may serve as an early marker for renal disease progression and could be evaluated as a target for therapeutic intervention to prevent renal failure in LN.
    Full-text · Article · Apr 2012 · Experimental and therapeutic medicine
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    ABSTRACT: The traditional method for assessing HLA antibodies in recipient serum samples is the complement-dependent cytotoxicity testing (CDC). Recently, the highly sensitive microbead-based Luminex assay was introduced and can detect low levels of anti-HLA Abs. To determine the impact of pretransplant donor-specific HLA antibodies (DSA) detectable by Luminex, despite a negative CDC crossmatch, on the outcomes of kidney transplantation. The correlation and cut-off value of panel reactive antibody (PRA) and DSA was also evaluated. Pre-transplant sera from 116 kidney transplant recipients with a negative CDC crossmatch were assessed for donor-specific HLA antibodies by using Luminex single antigen beads. The patients received kidney transplants at Ramathibodi Hospital between January 2003 and December 2007. The results were correlated with kidney graft outcomes. DSA were found in 24.1% (28/116) of all recipients. Of the twenty-eight DSA positive patients, four developed antibody-mediated rejection (AMR) (4/28 = 14.3%). All these 4 patients had positive C4d staining in their biopsies. Of the eighty-eight DSA negative patients, two developed AMR (2/88 = 2.3%). The AMR occurred more frequently in the DSA positive group than in the DSA negative group (14.3% versus 2.3%. The patient and graft survival were similar in both groups. The strength of pre-transplant DSA was not associated with the incidence of rejection episodes. There was a higher incidence of AMR in patients with pre-transplant DSA despite a negative CDC crossmatch. However, pre-transplant DSA detected by Luminex had no statistically significant impact on delayed graft function, patient survival and graft survival.
    Full-text · Article · Mar 2012 · Asian Pacific journal of allergy and immunology / launched by the Allergy and Immunology Society of Thailand
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    ABSTRACT: The complement-dependent lymphocytotoxicity crossmatch (CDC-XM) detects cytotoxic parameters of preformed antibodies. The flow cytometric crossmatch (FCXM) is used to detect the binding of recipient antibodies to donor cells. Because these two assays provide different information, both methods are often performed to assess the compatibility of donor-recipient pairs. The aim of this study was to develop a single assay that can simultaneously detect antibody binding and cytotoxicity. A procedure called cytotoxic flow cytometric crossmatch (cFCXM) that determines cell death and antibody binding simultaneously was developed. The assay was validated in parallel with extended incubation CDC-XM. Receiver operating characteristic analysis was used to determine the cut-off level. Furthermore, pretransplantation sera from seven recipients with pretransplantation donor-specific antibodies (DSA) and negative CDC-XM were retrospectively tested for cFCXM (4 without antibody-mediated rejection (AMR) and three with AMR). The optimal method for the simultaneous detection of antibody binding and cytotoxicity in a single assay has been determined. Four of four patients (100%) with pretransplantation DSA and without AMR had negative cFCXM in both parameters. Of three patients with pretransplantation DSA who developed AMR, two patients (66.7%) had positive B-cell cFCXM in both parameters, and 1 patient (33.3%) had positive T-cell cFCXM in a binding parameter only. The first patient had anti-DR9, DR53, DQ9, the second patient had anti-A11, DR12 and the last one had an anti-B46 in their pretransplantation sera. These 3 cases experienced biopsy-proven AMR after living-donor kidney transplantation. The newly developed assay, cFCXM, can simultaneously determine cytoxicity and antibody binding using a single platform. Furthermore, this assay can detect clinically significant HLA alloantibodies undetectable by conventional crossmatches. The cFCXM could serve as a new tool for the detection of a recipient's alloantibodies.
    Full-text · Article · Jan 2012 · Transplantation Proceedings
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    ABSTRACT: Renal phosphate wasting occurs early postkidney transplantation as a result of an accumulation of parathyroid hormone and fibroblast growth factor 23 from the CKD period. Serum phosphate, parathyroid hormone, and fibroblast growth factor 23 return to baseline 1 year postkidney transplantation. What happens beyond this period is unknown. Mineral parameters were obtained from 229 kidney transplant recipients at least 1 year posttransplantation; 46 normal subjects and 202 CKD patients with similar GFR served as controls. Factors associated with phosphate metabolism were analyzed. Despite the reduced graft function, most kidney transplant recipients had lower serum phosphate than normal subjects accompanied by renal phosphate loss. Fibroblast growth factor 23 was mostly lower or comparable with normal subjects, whereas parathyroid hormone was elevated in most patients. Hyperparathyroidism is also more common among kidney transplant recipients compared with CKD patients. Both parathyroid hormone and fibroblast growth factor 23 showed relationships with renal phosphate excretion, but only parathyroid hormone displayed an independent association. Parathyroid hormone showed the highest area under the curve in predicting renal phosphate leak. When patients were categorized according to parathyroid hormone and fibroblast growth factor 23 levels, only subset of patients with high parathyroid hormone had an increased renal phosphate excretion. Relatively low serum phosphate from renal phosphate leak continued to present in long-term kidney transplantation. Both parathyroid hormone and fibroblast growth factor 23 participated in renal tubular phosphate handling, but persistent hyperparathyroidism seemed to have a greater influence in this setting.
    Full-text · Article · Dec 2011 · Clinical Journal of the American Society of Nephrology
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    ABSTRACT: Abstract: FGF-23 is synthesized by osteocytes whose function is a regulation of phosphate (Pi) homeostasis through inhibition of renal Pi reabsorption and suppression of 1,25-OH-D synthesis. In chronic kidney disease (CKD), Pi retention occurs and the body compensates by augmenting the release of FGF-23 and PTH that will heighten renal Pi excretion alleviating Pi retention. CKD patients normally have elevated FGF-23 and PTH several folds that of normal subjects. Recent evidence added another organ specific role of FGF-23 in direct suppression of PTH secretion from parathyroid glands in response to hyperparathyroidism (HPT). During early period post kidney transplantation (KT), with recovering of kidney function, hypophosphatemia commonly occurs and is believed to be the result of renal Pi wasting secondary to immunosuppressive drugs as well as persistent HPT and FGF-23 accumulation from the CKD period. These mineral derangements resolve approximately 1 year post KT with the decline of FGF-23 and PTH towards the normal limits. Limited data is available regarding the involvement of FGF-23 and PTH in mineral abnormalities in long-term KT. The present study includes 229 patients who received KT for at least 1 year duration. FGF-23, PTH and other mineral parameters were measured and compared to 30 healthy subjects and 350 CKD patients with equivalent kidney function. The average GFR of KT patients was 56 ± 19 mL/min. Serum Pi was within or below the normal limits in 99% and high in 1%. When compared to CKD and normal subjects, KT recipients had lower serum Pi but higher serum Ca and PTH at all levels of renal function (GFR<=90 mL/min). Compared to normal subjects, FGF-23 was not elevated until later in the course of kidney disease in KT recipients (GFR<=30 mL/min). This data suggested that persistent HPT was likely responsible for low serum Pi in KT. Multivariate analysis confirmed the high PTH as an independent predictor for renal Pi excretion, whereas the significance of FGF-23 was lost after the adjustment with covariates. Instead, FGF-23 showed strong, positive and independent relationship with PTH and has highest AUC in predicting HPT in KT suggesting that its release might be mediated by the increase in PTH. In conclusion, low serum Pi persisted into late post KT period and was likely the result of persistent HPT rather than FGF-23 accumulation. The increase in FGF-23 appeared to associate with high PTH and its release may be mediated by HPT rather than Pi retention.
    No preview · Article · May 2011 · Bone
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    ABSTRACT: The renin-angiotensin system (RAS) and transforming growth factor β1 (TGF-β1) may play a role in the pathogenesis of fibrosis in kidney allografts. Experimental hyperuricemia shows activation of intrarenal RAS. However, the association between uric acid (UA), RAS, and TGF-β1 in allograft recipients has not been demonstrated. Therefore we investigated the association between serum UA levels, RAS, and TGF-β1 in kidney transplant recipients during the 1st year after transplantation. Sixty-two transplant recipients were included in the study. Serum UA level, plasma renin activity (PRA), and urine TGF-β1 concentration were studied at 3, 6, and 12 months after transplantation. Statistical correlation was demonstrated with the use of Spearman rank correlation coefficient. Receiver operating characteristic curve analysis and area under the curve were performed to assess the diagnostic performance to discriminate between estimated glomerular filtration rate (eGFR) <60 and ≥60 mL/min/1.73 m(2). For all 62 patients, urine TGF-β1 and serum UA had a tendency to increase during the 1-year follow-up period, despite no statistically significant change in eGFR. We found that increased urine TGF-β1 was correlated with rising serum UA levels and a decrease of the eGFR (r = 0.27 [P = .01]; r = -0.38 [P = .0003]). In contrast, there was no significant change in PRA and it was not correlated with eGFR or TGF-β1 (r = -0.01; P = .93). Increased urine TGF-β1 and serum UA level during the 1st year after transplantation correlated with a decline in eGFR. The evaluation of these parameters in the early post-transplantation period may identify patients at risk of allograft dysfunction. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Jul 2010 · Transplantation

  • No preview · Article · Jul 2010 · Transplantation
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    ABSTRACT: Coronary artery calcification (CAC) is prevalent among haemodialysis patients and predicts cardiovascular mortality. In addition to modifying traditional cardiovascular risk factors, therapy aimed at lowering serum phosphate and calcium-phosphate product has been advocated. Sodium thiosulfate, through its chelating property, removes calcium from precipitated minerals decreasing calcification burden in calcific uraemic arteriolopathy and soft tissue calcification. The effect of sodium thiosulfate on CAC in haemodialysis patients has never been studied. Eighty-seven stable chronic haemodialysis patients underwent multi-row spiral computed tomography and bone mineral density (BMD) measurement. Patients with a CAC score >or=300 were included to receive intravenous sodium thiosulfate infusion twice weekly post-haemodialysis for 4 months. CAC and BMD were re-evaluated at the end of the treatment course. Progression of CAC occurred in 25% and 63% of the patients in the treatment and control group, respectively (P = 0.03). CAC score was unchanged in the treatment group but increased significantly in the control group. BMD of the total hip declined significantly in the treatment group. In multivariate analysis adjusted for factors that influenced CAC progression, therapy with sodium thiosulfate was an independent protective factor (odds ratio = 0.05, P = 0.04). Major side effects were persistent anorexia and metabolic acidosis. The effect of sodium thiosulfate in delaying the progression of CAC is encouraging and will require a larger study. Determination of the safe therapeutic window is necessary in order to avoid bone demineralization.
    No preview · Article · Jun 2010 · Nephrology Dialysis Transplantation
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    ABSTRACT: Severe forms of hypertension are characterized by high blood pressure combined with end organ damage. Through the development and refinement of a transgenic rat model of malignant hypertension incorporating the mouse renin gene, we previously identified a quantitative trait locus on chromosome 10, which affects malignant hypertension severity and morbidity. We next generated an inducible malignant hypertensive model where the timing, severity, and duration of hypertension was placed under the control of the researcher, allowing development of and recovery from end organ damage to be investigated. We have now generated novel consomic Lewis and Fischer rat strains with inducible hypertension and additional strains that are reciprocally congenic for the refined chromosome 10 quantitative trait locus. We have captured a modifier of end organ damage within the congenic region and, using a range of bioinformatic, biochemical and molecular biological techniques, have identified angiotensin-converting enzyme as the modifier of hypertension-induced tissue microvascular injury. Reciprocal differences between angiotensin-converting enzyme and the anti-inflammatory tetrapeptide, N-acetyl-Ser-Asp-Lys-Pro in the kidney, a tissue susceptible to end organ damage, suggest a mechanism for the amelioration of hypertension-dependent damage.
    Preview · Article · Apr 2009 · Journal of Biological Chemistry
  • A Ingsathit · A Thakkinstian · S Kantachuvesiri · V Sumethkul
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    ABSTRACT: Previous studies had shown that HBV and HCV infections lead to increased morbidity and mortality after kidney transplantation when compared with the nonhepatitis group. However, few studies have compared the impact among a population with a high prevalence of HBV and HCV infections. We studied the outcomes of 346 recipients including 23 HBsAg (+) patients (6.6%; group 1), 22 patients with anti-HCV+ (6.3%, group 2), and 301 nonhepatitis patients (group 3) in a single center during a 6-year period. No patient had evidence of precirrhosis or cirrhosis before transplant. The primary end point was graft and patient survival rates. Secondary end point was the rate of progression of chronic allograft, nephropathy. The median follow-up time was 3.7 (0.5-6.8) years. Five-year actuarial graft survival was 80% for group 1, 61% for group 2, and 88 % for group 3 (P = .005). Cox regression showed HCV (hazards ratio 2.96; 95% CI = 1.03-8.51) and acute rejection episode (HR 3.01; 95%CI = 1.86-4.87) to be significant predictors of graft survival. Actuarial 5-year patient survival of group 1 was significantly lower than group 2 or group 3 (79 % vs 89% and 96%; P = .003). Cox regression revealed that the hazards ratio of HBV for death was 7.63 (95%CI = 1.88-30.86; P = .004). In contrast, HCV infection had no significant effect on patient survival (HR 1.59; 95%CI = 0.28-9.02). The rate of chronic allograft nephropathy progression was significantly faster in group 1 (-6.74 mL/min per year) and group 2 (-6.14 mL/min per year) than the controls. We concluded that HBV infection decreased patient survival earlier than HCV and that HCV decreased graft survival more significantly than HBV. Both HBV and HCV were associated with rapid progression of chronic allograft nephropathy. HBV was the strongest risk factor for mortality compared with HCV, with acute rejection episode, with diabetes mellitus, or other hazardous factors.
    No preview · Article · Jul 2007 · Transplantation Proceedings

Publication Stats

489 Citations
100.51 Total Impact Points

Institutions

  • 2009-2015
    • Mahidol University
      Siayuthia, Bangkok, Thailand
  • 2007-2013
    • Ramathibodi Hospital
      • Department of Diagnostic and Therapeutic Radiology
      Krung Thep, Bangkok, Thailand
  • 2002
    • Universität Heidelberg
      • Institute of Pharmacology
      Heidelburg, Baden-Württemberg, Germany