Publications by authors named "Ouppatham Supasyndh"

65 Publications

Cardio-ankle vascular index with renal progression and mortality in high atherosclerosis risk: a prospective cohort study in CORE-Thailand.

Clin Exp Nephrol 2021 Oct 13. Epub 2021 Oct 13.

Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand.

Background: Increased arterial stiffness is linked to markers of endothelial dysfunction and vasculopathy such as albuminuria, vascular calcification, left ventricular hypertrophy and cardiovascular (CV) diseases. Studies of arterial stiffness on renal progression are limited.

Objective: The study aimed to evaluate the association between high cardio-ankle vascular index (CAVI) and renal endpoint and all-cause mortality in a Thai population with high atherosclerosis risk.

Methods: A multicenter prospective cohort study was conducted among subjects with high CV risk or established CV diseases in Thailand. Subjects were divided into 3 groups with mean CAVI < 8, 8-8.9, and ≥ 9, respectively. Primary composite outcome consisted of estimated glomerular filtration rate (eGFR) decline over 40%, eGFR less than 15 mL/min/1.73 m, doubling of serum creatinine, initiation of dialysis and death related to renal causes. The secondary outcomes were all-cause mortality, CV mortality and eGFR decline.

Results: A total of 4898 subjects (2743 men and 2155 women) were enrolled. Cox proportional hazards model showed a significant relationship of high CAVI (CAVI ≥ 9) and primary composite outcome. Subjects with high CAVI at baseline had a 1.45-fold (95% CI 1.13-1.84) significant risk for the primary composite outcome and 1.72-fold (95% CI 1.12-2.63) risk for all-cause mortality, compared with normal CAVI (CAVI < 8). After stepwise multivariate analysis, the high CAVI group was only positively associated with primary composite outcome. Kaplan-Meier curve of the primary composite outcome and all-cause mortality demonstrated the worst survival in the high CAVI group (log-rank test with P < 0.05).

Conclusion: In a Thai cohort with high atherosclerosis risk, increased arterial stiffness was a risk factor for worsening renal function, including end-stage renal disease and initiation of dialysis.
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http://dx.doi.org/10.1007/s10157-021-02149-xDOI Listing
October 2021

Association of body mass index with kidney function and mortality in high cardiovascular risk population: A nationwide prospective cohort study.

Nephrology (Carlton) 2021 Aug 31. Epub 2021 Aug 31.

Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand.

Background: There is increasing awareness of the impact of obesity and underweight on cardiovascular (CV) disease, chronic kidney disease (CKD) and mortality. Abnormal body mass index (BMI) might be associated with worse clinical outcomes, including CKD progression, but limited evidence exists among Asian patients with high CV risk.

Objective: To investigate the association of BMI with progressive loss of kidney function and all-cause mortality in Thai patients with high CV risk.

Methods: In a national cohort of 5887 high CV risk subjects, we assessed the association of high BMI with the composite renal outcome (estimated glomerular filtration rate [eGFR] decline over 40%, eGFR less than 15 mL/min/1.73 m , doubling of serum creatinine, initiation of dialysis and death related to renal causes) and with all-cause mortality in Cox proportional hazards models.

Results: A total of 5887 participants (3217 male and 2670 female) with high CV risk were enrolled. Participants were classified into five groups by their baseline BMI; <20 kg/m (n = 482), 20-24.9 kg/m (n = 2437), 25-29.9 kg/m (n = 2140), 30-34.9 kg/m (n = 665) and 35 kg/m (n = 163), respectively. On multivariate analysis of Cox proportional hazards models, adjusted for other covariates, baseline BMI ≥35 kg/m was an independent predictor of loss of kidney function (HR 1.60, 95% CI 1.04-2.40) and all-cause mortality (HR 2.68, 95% CI 1.50-4.80). Baseline BMI <20 kg/m was an independent predictor of all-cause mortality as well (adjusted HR 2.26, 95% CI 1.50-3.42).

Conclusion: In the high CV risk Thai population, a BMI of 35 kg/m or more is associated with loss of kidney function and mortality. On the other hand, a BMI less than 20 kg/m is also associated with all-cause mortality.
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http://dx.doi.org/10.1111/nep.13970DOI Listing
August 2021

Efficacy of Lactulose versus Senna Plus Ispaghula Husk Among Patients with Pre-Dialysis Chronic Kidney Disease and Constipation: A Randomized Controlled Trial.

Int J Nephrol Renovasc Dis 2021 7;14:313-319. Epub 2021 Aug 7.

Division of Nephrology, Department of Internal Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand.

Background: Constipation is a common problem among patients with advanced chronic kidney disease (CKD), leading to a loss of quality of life. Pharmacologic treatments are in common use, but whether lactulose and senna plus ispaghula husk is effecive to treat constipation among patients with pre-dialysis CKD remains unknown.

Objective: The aim of the study was to compare efficacy of lactulose and senna plus ispaghula husk to treat constipation among patients with pre-dialysis CKD.

Methods: A study was conducted among patients with pre-dialysis CKD receiving a diagnosis of constipation by ROME IV criteria. All subjects were randomly assigned to receive either lactulose or senna plus ispaghula husk daily for 14 days. After a 7-day washout period, the patients were switched to the other substance for another 14 days. Primary outcome was complete spontaneous bowel movement (CSBM) weekly, assessed using a stool diary after each laxative. Secondary outcome measure was the change of stool appearance using the Bristol stool form scale (BSFS).

Results: A total of 22 patients underwent randomization. Baseline CSBM and BSFS were 3.4 ± 1.4 and 2.3 ± 1.2 time/week, respectively. At the end of the study, the mean CSBM weekly increased in the lactulose group (mean difference 1.3 ± 1.6, P < 0.001) and the senna plus ispaghula husk group (mean difference 2.1 ± 2.1, P < 0.001) from baseline. Comparing CSBM between lactulose and senna plus ispaghula husk exhibited no significant difference (95% CI -1.2 to 0.06; P = 0.276). BSFS was significantly changed after using ispaghula husk with senna, the mean ± SD of BSFS changed to 1.7 ± 1.8 (p = 0.001) and after use lactulose, the mean ± SD of BSFS changed to 1.6 ± 1.8 (p = 0.001). No significant BSFS change was observed between groups regarding stool appearance. No serious adverse event in either group was found.

Conclusion: Lactulose and senna plus ispaghula husk were similar in efficacy to treat constipation among patients with pre-dialysis CKD.

Trial Registration: Thai Clinical Trials number is TCTR20200818006. Retrospectively Registered 18 August 2020.
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http://dx.doi.org/10.2147/IJNRD.S328208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357401PMC
August 2021

Efficacy of high versus conventional dose of ergocalciferol supplementation on serum 25-hydroxyvitamin D and interleukin-6 levels among hemodialysis patients with vitamin D deficiency: A multicenter, randomized, controlled study.

Ther Apher Dial 2021 Aug 11. Epub 2021 Aug 11.

Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand.

Long-term dialysis involves a chronic inflammatory state and produces a high prevalence of vitamin D deficiency. A clinical trial was conducted in hemodialysis with serum 25-hydroxyvitamin D (25[OH]D) level <30 ng/ml. The conventional-group (N = 35) and the high-dose group (N = 35) were treated with ergocalciferol according to the K/DOQI guidelines and double dosage of ergocalciferol from the recommendation for 8 weeks, respectively. The main outcomes were measured by serum 25[OH]D and interleukin-6 (IL-6). At the end of 8 weeks, a statistically significant greater increase was observed of mean serum 25[OH]D levels and a decrease of mean parathyroid hormone levels in the high-dose group compared with the conventional-dose group. The high dose group had the higher achievement of vitamin D sufficiency than the conventional-dose group (97.4% vs. 76.4%, p = 0.012). No significant difference was found in mean changes of serum IL-6 level in both groups, except subgroup patients with vitamin D deficiency or serum 25[OH]D <20 ng/ml, high dose treatment suppressed serum IL-6 level (-2.67 pg/ml [IQR -6.56 to -0.17], p = 0.039). No differences were observed between the two groups in adverse events. Oral high-dose ergocalciferol supplementation has achieved higher vitamin D sufficiency than standard dose in end stage renal disease patients on dialysis.
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http://dx.doi.org/10.1111/1744-9987.13722DOI Listing
August 2021

Hyperuricemia and Impaired Renal Function: A Prospective Cohort Study.

Kidney Dis (Basel) 2021 May 6;7(3):210-218. Epub 2020 Nov 6.

Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand.

Background: Related studies have demonstrated a relationship of elevated serum uric levels with a decline in kidney function. However, limited evidence exists in a Southeast Asian community-based population.

Objective: The study aimed to examine the relationship between serum uric acid levels and impaired renal function.

Methods: A prospective cohort study was conducted in the Thai army health checkup population between July 1, 2006 and December 31, 2012. Inclusion criteria included age older than 20 years and baseline estimated glomerular filtration rate (eGFR) over 60 mL/min/1.73 m. Cox regression analysis was used to evaluate the association between incidence of impaired renal function and baseline serum uric acid quartiles. Impaired renal function was defined as eGFR <60 mL/min/1.73 m over 3 months.

Results: A total of 9,534 participants (7,474 men and 2,060 women) were enrolled. Cox regression analysis revealed a significant association of serum uric acid level with impaired renal function in the whole population as the unadjusted hazard ratio (HR) (95% CI) of impaired renal function in second, third, and fourth quartiles were 2.1 (1.39, 3.17), 2.39 (1.6, 3.59), and 3.94 (2.71, 5.74), respectively, when compared with serum uric acid in the first quartile, respectively. After adjusting in 2 models, the HR still significantly persisted with similar magnitudes in all quartiles. Higher incidences of impaired renal function were observed among males than among females in all quartiles. Kaplan-Meier curve showed better renal survival rate in the lower quartile groups. Linear regression analysis showed that eGFR negatively correlated with serum uric acid ( = -0.213, < 0.001).

Conclusion: Our study suggests that an independent association exists of serum uric acid levels with the incidence of impaired renal function and renal progression in the Southeast Asian community-based population.
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http://dx.doi.org/10.1159/000511196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216020PMC
May 2021

Effect of Oral carnosine supplementation on urinary TGF-β in diabetic nephropathy: a randomized controlled trial.

BMC Nephrol 2021 Jun 26;22(1):236. Epub 2021 Jun 26.

Department of Medicine, Division of Nephrology, Phramongkutklao Hospital and College of Medicine, Bangkok, 10400, Thailand.

Background: Activation of the transforming growth factor beta (TGF-β) pathway is a significant contributor to the pathogenesis of diabetic nephropathy. Carnosine is a dipeptide that can inhibit TGF-β synthesis. We tested the hypothesis that carnosine supplement added to standard therapy will result in reduced urinary TGF-β levels among patients with diabetic nephropathy.

Methods: We randomly assigned 40 patients with diabetic nephropathy and albuminuria 30-299 mg/day to treatment with carnosine (2 g/day) or placebo for 12 weeks. Urinary TGF-β level was determined using ELISA, urine albumin was ascertained by immunonephelometric assay, and renal function and metabolic profiles were determined at baseline and during 12 weeks of active treatment. Primary outcome was decrease in urinary levels of TGF-β.

Results: The 2 groups were comparable for baseline characteristics, blood pressure, urine albumin, urine TGF-β and renal function measurements. Urinary TGF-β significantly decreased with carnosine supplement (- 17.8% of the baseline values), whereas it tended to increase with placebo (+ 16.9% of the baseline values) (between-group difference P < 0.05). However, blood urea nitrogen, serum creatinine, glomerular filtration rate and other biochemical parameters remained unchanged during the study period including urinary albuminuria. Both groups were well tolerated with no serious side-effects.

Conclusions: These data indicated an additional renoprotective effect of oral supplementation with carnosine to decrease urinary TGF-β level that serves as a marker of renal injury in diabetic nephropathy.

Trial Registration: Thai Clinical Trials, TCTR20200724002 . Retrospectively Registered 24 July 2020.
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http://dx.doi.org/10.1186/s12882-021-02434-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235831PMC
June 2021

Efficacy of Weekly Split versus Single Doses of Ergocalciferol on Serum 25-Hydroxyvitamin D among Patients on Continuous Ambulatory Peritoneal Dialysis: A Randomized Controlled Trial.

Int J Nephrol 2021 13;2021:5521689. Epub 2021 Mar 13.

Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand.

Background: Vitamin D deficiency is a common problem among patients on continuous ambulatory peritoneal dialysis (CAPD). Vitamin D supplementation leads to reduced serum parathyroid hormone levels and improved cardiovascular markers. Different doses and time intervals of oral vitamin D supplementation may differ in each patient on dialysis. The study aimed to evaluate the efficacy of weekly split and single dose of ergocalciferol at 60,000 IU on serum 25-hydroxyvitamin D (25(OH)D) among patients on CAPD.

Methods: A randomized study was conducted among patients on CAPD with vitamin D deficiency or insufficiency (25(OH)D < 30 ng/mL). Patients were randomly assigned to two groups: the split dose group was given ergocalciferol 20,000 IU three times weekly and the single dose group was given ergocalciferol 60,000 IU once weekly for 8 weeks. Main outcomes measured serum 25(OH)D concentrations, serum calcium, serum phosphate, and intact parathyroid levels at 8 weeks after being enrolled.

Results: Of 128 screened patients, 50 met the criteria for eligibility and were randomized. At 8 weeks after treatment, mean serum 25(OH)D concentrations significantly increased from baseline 22.7 ± 5.9 to 29.5 ± 9.5 ng/mL (=0.004) in the split dose group and 22.9 ± 5.3 to 31.2 ± 12.3 ng/mL (=0.003) in the single dose group. No significant change was found in increase of serum 25(OH)D between the two groups (=0.561). At the end of study, a similar proportion of patients in both groups reached the desirable serum concentration of 25(OH)D ≥ 30 ng/mL (60% in the single group vs. 40% in the split group, =0.258). No significant cases of hypercalcemia, hyperphosphatemia, or serious adverse events occurred during the study.

Conclusion: Weekly single and split doses of ergocalciferol 60,000 IU achieved similar effects on serum 25(OH)D levels among patients on CAPD with vitamin D insufficiency or deficiency, suggesting that weekly single dose would be prescribed for adequate vitamin D repletion. This trial is registered with TCTR20200821005.
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http://dx.doi.org/10.1155/2021/5521689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984910PMC
March 2021

Revised ISN/RPS 2018 classification of lupus renal pathology predict clinical remission.

Int Urol Nephrol 2021 Jul 8;53(7):1391-1398. Epub 2021 Mar 8.

Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, 10400, Thailand.

Background: A precise description of renal histological lesions and an appropriate classification of lupus nephritis are both essential for nephrologists to guide treatment and predict prognosis among patients. The prognostic value of ISN/RPS 2003 classification is controversial. A new classification for lupus nephritis was recently proposed, namely, the revised ISN/RPS 2018 classification.

Objective: The study aimed to evaluate the predictive value of the clinical and pathological factors according to ISN/RPS 2018 classification on renal remission among patients with proliferative lupus nephritis.

Methods: A total number of 41 patients with proliferative lupus nephritis on adequate renal biopsy specimen between 2017 and 2018 were included. Clinical and histological variables were tested for their association with renal remission. Univariate and multivariate logistic regression analysis were performed to identify independent predictors of renal remission after 24 weeks of induction therapy.

Results: After induction therapy, 56.1% of patients reached complete and partial remission and 43.9% reached no remission. In univariate analyses, baseline glomerular filtration rate (GFR), presence of anti-DNA titer, cellular crescents, interstitial inflammation, glomerulosclerosis, interstitial fibrosis, tubular atrophy and total chronicity index strongly impacted renal response. After multivariate logistic regression analysis, we identified aging, presence of cellular crescents, and high total renal chronicity index as independent predictors of renal remission. Receiver operating characteristic (ROC) analysis revealed that baseline estimated GFR (AUC = 0.708; 95% CI 0.527-0.888), anti-DNA titer (AUC = 0.674; 95% CI 0.491-0.858), cellular crescent (AUC = 0.750; 95% CI 0.585-0.915) and renal chronicity index (AUC = 0.765; 95% CI 0.585-0.915) predicted renal remission. Combining all factors achieved a perfect score predicting renal response (AUC 0.924; 95% CI 0.840-1.000).

Conclusion: The study identified baseline GFR, anti-DNA titer, cellular crescent, and high chronicity index according to revised ISN/RPS 2018 classification as important predictors of renal response after induction therapy in proliferative lupus nephritis.
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http://dx.doi.org/10.1007/s11255-020-02732-3DOI Listing
July 2021

Effectiveness of renal-specific oral nutritional supplements compared with diet counseling in malnourished hemodialysis patients.

Int Urol Nephrol 2021 Aug 16;53(8):1675-1687. Epub 2021 Jan 16.

Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand.

Background: Malnutrition is highly prevalent and a consequence of inflammation and related comorbidities among patients on maintenance hemodialysis. Oral nutritional supplementation (ONS) is recommended for malnourished patients with kidney failure. The study aimed to evaluate renal-specific oral nutrition (ONCE dialyze) supplement on nutritional status in patients on hemodialysis.

Methods: Patients were randomized into 3 groups; treatment groups received 370 kcal/day of ONCE Dialyze (N = 26) or 370 kcal/day of NEPRO (N = 30) for 30 days. The control group (N = 24) received no intervention. All patients were counseled by the same registered dietitian during the study. The nutritional status was evaluated using malnutrition inflammation score (MIS) assessment, body compositions, serum albumin and pre-albumin levels at baseline and 30 days.

Results: Eighty patients were analyzed with mean age of 57.2 ± 15.9 years. The intervention group exhibited significant improvements in energy, protein, fat, fiber and magnesium intake by dietary interview compared with the control group. Percentage of changes in MIS was - 29.0% (95% CI - 40.5 to - 17.4), - 23.9% (95% CI - 37.2 to - 10.6) and 12.1% (95% CI - 19.2 to 43.4) for the ONCE dialyze, NEPRO and control groups, respectively (overall P = 0.006). Percentage of changes in serum albumin was 5.3% (95% CI 1.9-8.7), 3.3% (95% CI - 0.1 to 6.7) and - 0.8% (95% CI - 4.3 to 2.7) for the ONCE dialyze, NEPRO, and control groups, respectively (overall P = 0.039; P = 0.043 for ONCE dialyze vs. control). No serious adverse effects were reported in any group.

Conclusion: Dietary advice combined with ONS especially ONCE dialyze was associated with improved MIS, serum albumin, dietary energy and macronutrient intake among patients with kidney failure on maintenance hemodialysis.

Clinical Trial Registration: TCTR20200801001.
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http://dx.doi.org/10.1007/s11255-020-02768-5DOI Listing
August 2021

Impaired Glomerular Filtration Rate in Type 2 Diabetes Mellitus Subjects: A Nationwide Cross-Sectional Study in Thailand.

J Diabetes Res 2020 12;2020:6353949. Epub 2020 Aug 12.

Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand.

Background: Type 2 diabetic mellitus (T2DM) patients with impaired renal function have a higher risk of mortality, and often progress to end-stage renal disease. The study aims to determine the prevalence of kidney disease and investigate the relationship between various factors and impaired renal function in a large population of patients with T2DM.

Methods: We conducted a cross-sectional study among 30,377 patients from a nationwide diabetes study involving 602 Thai hospitals. Impaired glomerular filtration rate (GFR) was defined as <60 mL/min per 1.73 m. Multivariate logistic regression was used to determine the association between standard risk factors and impaired GFR.

Results: The prevalence of impaired GFR in a T2DM population was 39.2%. After adjusting for multiple risk factors, advanced age (adjusted OR 11.69 (95%CI = 3.13 to 43.61)), macroalbuminuria (adjusted OR 3.54 (95%CI = 1.50 to 8.40)), high serum uric acid (adjusted OR 2.06 (95%CI = 1.73 to 2.46)), systolic BP 130-139 mmHg (adjusted OR 3.21 (95%CI = 1.30 to 7.96)), hemoglobinA1C (HA1C) <6% (adjusted OR 3.71 (95%CI = 1.65 to 8.32)), and HA1C >7% (adjusted OR 2.53 (95%CI = 1.38 to 4.63)) were found to be associated with a significantly increased risk of impaired GFR among T2DM patients.

Conclusion: Almost 40% of patients with T2DM in a nationwide cross-sectional study in Thailand had impaired GFR. Advanced age, albuminuria, hyperuricemia, hypertension, HA1C <6%, and HA1C >7% were independently associated with increased prevalence of impaired GFR.
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http://dx.doi.org/10.1155/2020/6353949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443026PMC
July 2021

Renal Effects of Sulodexide in Type 2 Diabetic Patients without Nephrotic Range Proteinuria.

J Diabetes Res 2020 8;2020:2984680. Epub 2020 Aug 8.

Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand.

Background: Glycosaminoglycan plays an important role in the maintenance of glomerular charge selectivity of diabetic nephropathy. Sulodexide, a mixture of naturally occurring glycosaminoglycan polysaccharide components, has shown a nephroprotective effect in an experimental model of diabetic nephropathy. Although sulodexide reduced albuminuria in patients with type 1 and type 2 diabetes, long-term effects in patients with type 2 diabetes with significant proteinuria have not been established.

Objectives: The study was aimed at investigating the effects of sulodexide on proteinuria and renal function in patients with type 2 diabetes and nephropathy.

Methods: Fifty-two patients with proteinuria between 500 and 3000 mg/day received sulodexide 200 mg/day for 12 months, while 56 matched patients with type 2 diabetes constituted the control group. All patients received standard metabolic and blood pressure controls. Primary outcome was evaluated as percentage of reduced proteinuria compared with the control group. Renal function was assessed using estimated glomerular filtration rate (GFR).

Results: Proteinuria significantly increased in the control group [0.9 (IQR 0.3 to 1.78) to 1.16 (IQR 0.44 to 2.23) g/gCr, = 0.001], whereas it remained stable in the sulodexide group [0.66 (IQR 0.23 to 0.67) to 0.67 (IQR 0.17 to 1.51) g/gCr, = 0.108]. At 12 months, proteinuria was higher by 19.4% (IQR 10.3 to 37.6) in the control group while proteinuria was lower by -17.7% (IQR -53.1 to 3.2) in the sulodexide group with a significant difference between groups ( = 0.001). Renal function was noted as a change of estimated GFR, and serum creatinine decreased significantly during the study in both groups but did not significantly differ between groups. No significant changes in the blood pressure, fasting plasma glucose, and hemoglobin A1C were reported.

Conclusion: In addition to standard treatment, sulodexide is efficient in maintaining proteinuria in patients with type 2 diabetes with nonnephrotic range proteinuria, but it did not provide an additional benefit concerning renal disease progression.
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http://dx.doi.org/10.1155/2020/2984680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439194PMC
July 2021

A randomized controlled study of dose-finding, efficacy, and safety of mulberry leaves on glycemic profiles in obese persons with borderline diabetes.

Complement Ther Med 2020 Mar 31;49:102292. Epub 2019 Dec 31.

Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand; Bioactive Resources for Innovative Clinical Applications Research Unit, Chulalongkorn University, Bangkok, Thailand. Electronic address:

Objectives: Mulberry (Morus alba L.) leaves have been used in traditional medicine for treating hyperglycemia. However, there remains difficulties in the implementation of mulberry leaves in evidence-based practice. The aims of this study were to examine the optimal dose of 1-deoxynojirimycin (DNJ) in mulberry leaves and to determine the efficacy and safety of mulberry leaves in glycemic control in obese persons with borderline diabetes.

Design: First, healthy adults were recruited into the dose-finding study and randomly allocated to ingest sucrose solution concurrently with mulberry leaf powder at weights equivalent to 0 (control), 6, 12, and 18 mg of DNJ. Postprandial glucose and undesirable effects were evaluated. Second, obese persons with borderline diabetes were randomly assigned into the mulberry-leaves treatment group (12 mg of mulberry DNJ three times daily) and the control group in the 12-week prospective study. Blood glucose and insulin as well as adverse effects were determined.

Results: Twelve mg of mulberry DNJ was the minimum effective dose attenuating postprandial hyperglycemia. Mulberry leaves decreased fasting plasma glucose (FPG) by 3.86 ± 5.99 mg/dL (p = 0.002) and glycated hemoglobin (HbA1c) by 0.11 ± 0.22 % (p = 0.011) when compared with the baseline levels. Improvement in glucose tolerance was not observed. Furthermore, mulberry leaves tended to ameliorate insulin resistance (p = 0.057). Adverse events of mulberry leaves commonly found in this study were gastrointestinal symptoms including bloating, flatulence, and loose stools.

Conclusion: Mulberry leaves possessed favorable effects on glycemic profiles without serious side effects.
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http://dx.doi.org/10.1016/j.ctim.2019.102292DOI Listing
March 2020

Effectiveness of Dose Adjustment of Insulin in Type 2 Diabetes among Hemodialysis Patients with End-Stage Renal Disease: A Randomized Crossover Study.

J Diabetes Res 2019 13;2019:6923543. Epub 2019 Nov 13.

Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok 10400, Thailand.

Determining insulin requirements for hemodialysis patients with end-stage renal disease (ESRD) is difficult. We performed a randomized crossover study among type 2 diabetes (T2DM) patients with ESRD on continuous hemodialysis and receiving standard insulin for glycemic control. The patients were randomized in 2 groups: daily insulin needed on the day after hemodialysis and a 25% decrease in daily insulin needed on the day after hemodialysis. A total of 51 T2DM patients with ESRD were enrolled. The adjusted-insulin group had higher plasma glucose levels at the 2nd hour of dialysis than those of the nonadjusted-insulin group. Incidence of hypoglycemia per dialysis session (3.3% vs. 0.7%, = 0.02) and symptoms related to hypoglycemia (6.9% vs. 0.7%, = 0.001) were more frequent in the nonadjusted-insulin group. A reduced insulin administration of 25% among T2DM patients undergoing hemodialysis on the day of dialysis was associated with sustained glycemic efficacy and the production of fewer hypoglycemic symptoms. This trial is registered with TCTR20180724002.
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http://dx.doi.org/10.1155/2019/6923543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885192PMC
June 2020

Role of TCF7L2 and PPARG2 Gene Polymorphisms in Renal and Cardiovascular Complications among Patients with Type 2 Diabetes: A Cohort Study.

Kidney Dis (Basel) 2019 Oct 6;5(4):220-227. Epub 2019 Mar 6.

Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand.

Background: The emerging renal and cardiovascular complications of type 2 diabetes (T2DM) genetics involves differently assembled gene variants including transcription factor 7-like 2 (TCF7L2) and peroxisome proliferator-activated receptor gamma 2 (PPARG2) polymorphisms. However, the relevance of these genes for complication prediction has not been extensively tested.

Methods: We analyzed the SNP rs7903146 variants in TCF7L2 and PPARG2 gene polymorphisms for their contribution to the incidence of chronic kidney disease (CKD) and cardiovascular complications in a prospective cohort study. All T2DM patients were followed up to estimate the glomerular filtration rate and cardiovascular outcomes. Cox proportional hazards regression models were used to estimate the genotype effect on the incidence of CKD and vascular complications.

Results: A total of 422 patients were included. SNP rs7903146 variants in the TCF7L2 gene were classified into 3 groups: CC, 385 patients (91.2%), CT, 32 patients (7.6%), and TT, 5 patients (1.2%), while in the PPARG2 gene they were classified into 2 groups: Pro12Pro, 404 patients (95.7%) and Pro12Ala, 18 patients (4.3%). The prevalence of CKD, cardiovascular disease, and death at the end of the 5-year follow-up was 16.8, 29, and 7.9%, respectively. The Pro12Ala variant of the PPARG2 gene was significantly associated with increased CKD risk at the end of the study (adjusted HR 3.45, 95% CI 1.01-11.77, = 0.046); it showed a significant association with increased cerebrovascular risk, but not cardiovascular disease and mortality. No genotype effect of rs7903146 in the TCF7L2 gene was apparent on renal and cardiovascular complications, except the TT variant of rs7903146 increased cardiovascular events when compared with the non-TT variant.

Conclusion: The findings of our study were that the Pro12Ala variant in the PPARG2 gene was associated with risk of developing CKD and cerebrovascular disease in Asian T2DM subjects in a prospective cohort study. The TCF7L2 polymorphism was not associated with cardiovascular outcomes.
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http://dx.doi.org/10.1159/000497100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6873022PMC
October 2019

Arterial Stiffness Predicts Rapid Decline in Glomerular Filtration Rate Among Patients with High Cardiovascular Risks.

J Atheroscler Thromb 2020 Jun 10;27(6):611-619. Epub 2019 Oct 10.

Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine.

Aims: Arterial stiffness is known to be an important surrogate marker for atherosclerosis and predictor of peripheral vascular and cardiovascular (CV) disease. Whether high cardio-ankle vascular index (CAVI) is associated with the development of rapid glomerular filtration rate (GFR) decline remains uncertain. The study aimed to determine the relationship between CAVI and renal function progression among patients with high CV risk.

Methods: This study employed a prospective cohort design with 1-year follow-up among patients with high CV risk. Arterial stiffness was measured using CAVI method. GFR was estimated using the chronic kidney disease (CKD) epidemiology collaboration equation, and rapid decline in GFR was defined with decrease in GFR ≥ 5 mL/min/1.73 m yearly.

Results: Of 352 patients with mean age 67.8±10.1 years, 224 patients (63.6%) were suspected to have arteriosclerosis (CAVI ≥ 9), and 208 patients (59.1%) had CKD (GFR <60 mL/min/1.73 m). Annual decline of GFR was -0.75 [interquartile range (IQR), -1.16 to 6.08] mL/min/1.73 m/year, and 30.1% of patients experienced a rapid decline in GFR. Compared with normal CAVI (CAVI <8), high CAVI (CAVI ≥ 9) and borderline CAVI (CAVI 8-8.9) in all subjects and subgroup of baseline GFR >60 mL/min/1.73 m were associated with rapid GFR decline. Multivariable analysis showed that high CAVI and borderline CAVI were associated with 2.47-fold (95% CI, 0.89-6.84; P=0.082) and 4.04-fold (95% CI, 1.46-11.18; P=0.007) increased odds ratio of rapid GFR decline, respectively.

Conclusion: Among patients with high risk of CV with or without CKD, high CAVI (cut point of ≥ 9) was independently associated with a rapid decline in GFR, suggesting that systemic vascular stiffness predicted a decrease in renal function in this population.
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http://dx.doi.org/10.5551/jat.52084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355103PMC
June 2020

Urinary biomarkers of tubular injury to predict renal progression and end stage renal disease in type 2 diabetes mellitus with advanced nephropathy: A prospective cohort study.

J Diabetes Complications 2019 09 25;33(9):675-681. Epub 2019 May 25.

Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand.

Background: Novel potential tubular biomarkers in diabetic nephropathy could improve risk stratification and prediction. The study aimed to evaluate the association of tubular damage markers with rapid renal progression and incidence of end stage renal disease (ESRD) in type 2 diabetes (T2DM).

Methods: A prospective cohort study, involving a total of 257 patients with T2DM, was included. The baseline values of urine albumin, cystatin-C, angiotensinogen, kidney injury molecule-1 (KIM-1) and neutrophil-gelatinase associated lipocalin (NGAL) were measured. The composite outcomes included a rapid glomerular filtration rate (GFR) decline or incident of ESRD at 3-year follow-up.

Main Findings: The composite outcomes were noted in 26.1%. Using univariate followed by multivariate COX proportional hazard regression analysis, the patients with highest quartiles of urine cystatin-C (HR 2.96, 95% CI, 1.38-6.35), urine angiotensinogen (HR 2.93, 95% CI, 1.40- 6.13) urine KIM-1 (HR 2.77, 95% CI, 1.27-6.05) and urine NGAL (HR 2.53, 95% CI, 1.11-5.76) were significantly associated with rapid renal progression when compared with the patients with the lowest quartiles of all tubular biomarkers.

Conclusions: Patients with T2DM with high levels of baseline urine tubular biomarkers (cystatin-C, angiotensinogen, KIM-1 and NGAL) had a greater incidence of ESRD and rapid GFR decline.
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http://dx.doi.org/10.1016/j.jdiacomp.2019.05.013DOI Listing
September 2019

Effect of sodium-glucose cotransporter 2 inhibitor on proximal tubular function and injury in patients with type 2 diabetes: a randomized controlled trial.

Clin Kidney J 2019 Jun 4;12(3):326-332. Epub 2019 Jan 4.

Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand.

Background: Intensive glucose control reduces the risk for microvascular complications in type 2 diabetes (T2DM). Recently, sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to exert renoprotection beyond glycemic control, although their effects on the organs are not well known. There are limited data on SGLT2 inhibitors for the biomarkers of kidney injury in type 2 diabetes mellitus (T2DM) patients.

Objective: Our objective was to demonstrate the effect of SGLT2 inhibitors on proximal tubular injury and function in patients with T2DM.

Methods: T2DM patients with persistent glycated hemoglobin (HbA1c) levels >7% were randomly assigned to either dapagliflozin 10 mg/day ( = 28) or standard treatment ( = 29) for 12 weeks. Proximal tubular injury biomarkers, including urine kidney injury molecule-1:creatinine ratio (UKIM1CR), urine cystatin C:creatinine ratio (UCCR), urine albumin:creatinine ratio (UACR), fractional excretion of phosphate (FEPO) and fractional excretion of uric acid (FEUA) were measured at baseline and study end.

Results: Baseline characteristics were comparable between treatment groups. After 12 weeks, dapagliflozin-treated versus standard-treated patients showed reductions in HbA1c (-0.75 ± 0.21 versus -0.70 ± 0.25%; P = 0.882). There were significant between-group differences in the reduction in UACR {-23.3 [95% confidence interval (CI) -44.4 to -2.2] versus +19.9 (-4.0-43.8) mg/g Cr; P = 0.010} and UKIM1CR [-26.7 (95% CI -232.9-179.5) versus +422.2 (46.7-797.7) ng/g Cr; P = 0.047], but no significant difference in changes in UCCR between the two groups. There was no significant change in glomerular filtration rate, serum phosphate level, FEUA and FEPO in the dapagliflozin group. No serious renal-related adverse events were observed in either group.

Conclusions: This study indicates that dapagliflozin in T2DM patients can decrease the levels of urinary proximal tubular injury biomarkers, thus highlighting its renoprotective effect. SGLT2 inhibitors could prove useful in treating T2DM by protecting against renal tubular injury and may lead to reduced long-term renal outcomes.
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http://dx.doi.org/10.1093/ckj/sfy122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6543969PMC
June 2019

The authors' reply.

Kidney Res Clin Pract 2019 Mar;38(1):125-126

Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand.

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http://dx.doi.org/10.23876/j.krcp.19.006DOI Listing
March 2019

Very low protein diet plus ketoacid analogs of essential amino acids supplement to retard chronic kidney disease progression.

Kidney Res Clin Pract 2018 Dec 31;37(4):384-392. Epub 2018 Dec 31.

Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand.

Background: A very low protein diet (VLPD) with ketoacid analogs of essential amino acids (KA/EAA) administration can remarkably influence protein synthesis and metabolic disturbances of patients with advanced chronic kidney disease (CKD), and may also slow the decline in renal function.

Methods: A retrospective cohort study was carried out to monitor renal progression and metabolic and nutritional status among 140 patients with CKD stage III or IV. One group (n = 70) was on a low protein diet (LPD) with 0.6 g of protein intake, and another group (n = 70) was on a VLPD with 0.3 g of protein and KA/EAA supplementation of 100 mg/kg/day for 12 months.

Results: At 12-month follow-up, estimated glomerular filtration rate (GFR) significantly decreased from 41.6 ± 10.2 to 36.4 ± 8.8 mL/min/1.73 m ( < 0.001) and urine protein increased from 0.6 ± 0.5 to 0.9 ± 1.1 g/day ( = 0.017) in the LPD group, but no significant changes in estimated GFR and urine protein were found in the VLPD plus KA/EAA group. A significant mean difference in rate of change in estimated GFR (-5.2 ± 3.6 mL/min/1.73 m per year; < 0.001) was observed between the two groups. After Cox regression analysis, treatment with VLPD plus KA/EAA significantly protected against the incidence of declining GFR > 10% annually (adjusted hazard ratio, 0.42; 95% confidence interval, 0.23-0.79; = 0.006) and significant correlations were found between using VLPD plus KA/EEA and increased GFR.

Conclusion: VLPD supplementation with KA/EAA is associated with delayed renal progression while preserving the nutritional status in the patients with CKD. Co-administration of VLPD and KA/EAA may prove an effective alternative to conservative management of CKD.
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http://dx.doi.org/10.23876/j.krcp.18.0055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312769PMC
December 2018

Safety and efficacy of low dose pioglitazone compared with standard dose pioglitazone in type 2 diabetes with chronic kidney disease: A randomized controlled trial.

PLoS One 2018 31;13(10):e0206722. Epub 2018 Oct 31.

Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand.

Background: Choices of hypoglycemic agents for patients with type 2 diabetes and chronic kidney disease (CKD) are limited. Available data among patients with CKD suggest that pioglitazone was effective and safe, with no increase in serious adverse effects. However, weight gain and fluid retention are major clinical problems for pioglitazone among patients with CKD. We conducted this study to compare the efficacy and side effects of low dose pioglitazone with standard dose pioglitazone among patients with type 2 diabetes and CKD.

Methods: A total of 75 patients with type 2 diabetes and CKD and inadequate glycemic control receiving any pharmacological antidiabetic treatment were randomly assigned to 2 groups. One group consisted of 37 patients treated with standard dose pioglitazone (15 mg/day) and another group consisted of 38 patients treated with low dose pioglitazone (7.5 mg/day). Glycosylated hemoglobinA1c (HbA1c) and metabolic profiles were monitored every 8 weeks for 24 weeks. Body composition was assessed using bio-electrical impedance analysis (BIA).

Results: After 6 months of therapy, HbA1c levels decreased in both standard and low dose pioglitazone groups. The mean changes in HbA1c for standard and low dose pioglitazone were 1.1±1.6 and -1.4±1.5 (P = 0.543), respectively. Compared with low dose pioglitazone, standard dose pioglitazone treatment led to a greater increase in body weight, fat mass, total body water and extracellular water composition. No major adverse effects including hypoglycemia, congestive heart failure and abnormal liver function were identified.

Conclusion: Pioglitazone 7.5 mg once daily treatments presented similar glycemic control to standard dose pioglitazone and exhibited beneficial effects on weight gain and fluid retention among patients with type 2 diabetes and CKD.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0206722PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209355PMC
April 2019

Efficacy and safety of subcutaneous administration of lyophilized powder of alfa-erythropoietin to maintain hemoglobin concentrations among hemodialysis patients.

Int J Nephrol Renovasc Dis 2017 20;10:275-283. Epub 2017 Sep 20.

Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand.

Background: Anemia associated with chronic kidney disease (CKD) often requires treatment with recombinant human erythropoietin (EPO). This study investigated the therapeutic equivalence between lyophilized powder and standard liquid EPO alfa by subcutaneous (SC) administration in hemoglobin maintenance among patients on hemodialysis.

Methods: This was a single-blinded, randomized, controlled, single-center, parallel-group study regarding the treatment of anemia among CKD patients on hemodialysis and being treated with stable doses of EPO alfa at least for 12 weeks. Anemic hemodialysis patients (n=63) received standard liquid or lyophilized powder EPO alfa for 24 weeks by SC administration. Achievement of the target hemoglobin concentration and safety and tolerability end points were documented.

Results: Baseline mean hemoglobin level was 11.1±0.7 g/dL using lyophilized powder EPO alfa and 11.2±0.9 g/dL using standard liquid EPO alfa. The baseline median dose of EPO alfa was 126.4 (interquartile range [IQR] 81.6-163.6) U/kg/week in the lyophilized powder EPO alfa group and 116.9 (IQR 76.5-144.1) U/kg/week in the standard liquid EPO alfa group. Treatment with SC lyophilized powder EPO alfa maintained mean hemoglobin and hematocrit concentrations after switching from standard liquid EPO alfa. No statistical significance between groups was reported for hemoglobin concentrations and weekly dose of EPO alfa during the study. No safety concerns were raised, including positive anti-EPO antibodies.

Conclusion: In this study of anemia therapy among patients with end-stage renal disease on hemodialysis therapy, the SC injection of lyophilized powder EPO alfa was well tolerated and effectively maintained hemoglobin levels. Future studies of larger size and longer duration will be required to assess safety profiles.
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http://dx.doi.org/10.2147/IJNRD.S143731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5614773PMC
September 2017

Efficacy and Safety of Sacubitril/Valsartan (LCZ696) Compared With Olmesartan in Elderly Asian Patients (≥65 Years) With Systolic Hypertension.

Am J Hypertens 2017 Nov;30(12):1163-1169

Osaka University Graduate School of Medicine, Osaka, Japan.

Objective: Systolic hypertension is common in elderly patients and remains a challenge to treat effectively. The efficacy and safety of sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor neprilysin inhibitor, vs. olmesartan was evaluated in elderly Asian patients (≥65 years) with systolic hypertension.

Methods: In this randomized, double-blind, 14-week study, patients initially received once-daily sacubitril/valsartan 100 mg or olmesartan 10 mg, increased to sacubitril/valsartan 200 mg or olmesartan 20 mg at week 4. At week 10, for patients with blood pressure (BP) >140/90 mm Hg, the doses were up-titrated to sacubitril/valsartan 400 mg or olmesartan 40 mg. The primary assessment was superiority of sacubitril/valsartan vs. olmesartan in reducing office mean sitting (ms) systolic BP (msSBP) from baseline at week 10. Secondary efficacy assessments included changes from baseline in ms diastolic BP (msDBP), ms pulse pressure (msPP), 24-hour mean ambulatory (ma) BP (maBP), and maPP at week 10; msBP and msPP at weeks 4 and 14.

Results: Overall, 588 patients were randomized (mean age, 70.7 years; baseline msBP, 160.3/84.9 mm Hg; msPP, 75.4 mm Hg). At week 10, sacubitril/valsartan provided superior msSBP reductions vs. olmesartan (22.71 vs. 16.11 mm Hg, respectively; P < 0.001); similarly, reductions from baseline in other BP and PP assessments were significantly greater with sacubitril/valsartan. At week 14, despite more patients requiring up-titration in the olmesartan group, msBP and msPP reductions from baseline were significantly greater with sacubitril/valsartan. Both treatments were generally well-tolerated.

Conclusion: Sacubitril/valsartan is more effective than olmesartan in reducing BP in elderly Asian patients with systolic hypertension.
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http://dx.doi.org/10.1093/ajh/hpx111DOI Listing
November 2017

Adding C-reactive protein and procalcitonin to the model of end-stage liver disease score improves mortality prediction in patients with complications of cirrhosis.

J Gastroenterol Hepatol 2018 Mar;33(3):726-732

Division of Gastroenterology and Hepatology, Mayo Clinic, College of Medicine, Rochester, Minnesota, USA.

Background And Aim: This study aims to determine the performance of models adding C-reactive protein (CRP) and procalcitonin (PCT) to the model of end-stage liver disease (MELD) score for mortality prediction in patients hospitalized with complications of cirrhosis.

Methods: A prospective cohort study was carried out in consecutive cirrhotic patients admitted with complications of cirrhosis between September 2012 and December 2013 at Phramongkutklao Hospital, Bangkok, Thailand. All patients had venous CRP, PCT, and laboratory values for MELD score calculation measured at emergency room or admission. Cox regression analysis and the c-statistic were used to predict mortality. The MELD-CRP score was externally validated in 818 eligible patients from Mayo Clinic, Rochester, using data from 1288 cirrhotic patients diagnosed between 2010 and 2014.

Results: A cohort of 177 patients with cirrhosis was admitted during the study period. Seventy-one patients were eligible for analysis. The MELD score was predictive of 90-day mortality odds ratio (OR) 1.19 (95% confidence interval [CI] 1.09-1.32). Adding CRP and/or PCT to the MELD score improved the predictive of 90-day mortality: MELD-CRP OR 2.71 (95% CI 1.66-4.99); MELD-PCT OR 2.72 (95% CI 1.66-4.99); MELD-CRP-PCT OR 2.71 (95% CI 1.67-4.92). The c-statistics for MELD, MELD-CRP, MELD-PCT, and MELD-CRP-PCT were 0.81, 0.83, 0.84, and 0.85, respectively. Adding CRP and/or PCT to the MELD score also improved 30-day mortality prediction. Similar results for the MELD-CRP score were obtained from the Mayo Clinic external validation cohort.

Conclusion: The MELD-CRP, MELD-PCT, and MELD-CRP-PCT scores may be superior to the MELD score alone in predicting mortality in patients hospitalized with complications of cirrhosis.
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http://dx.doi.org/10.1111/jgh.13928DOI Listing
March 2018

Urine neutrophil gelatinase-associated lipocalin to predict renal response after induction therapy in active lupus nephritis.

BMC Nephrol 2017 Aug 4;18(1):263. Epub 2017 Aug 4.

Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, 315 Rachavitee Road, Phyathai, Bangkok, 10400, Thailand.

Background: Tubulointerstitial injury is important to predict the progression of lupus nephritis (LN). Urine neutrophil gelatinase-associated lipocalin (NGAL) has been reported to detect worsening LN disease activity. Thus, urine NGAL may predict renal outcomes among lupus patients.

Methods: We conducted a prospective multi-center study among active LN patients with biopsy-proven. All patients provided urine samples for NGAL measurement by ELISA collected from all patients at baseline and at 6-month follow-up after induction therapy.

Results: In all, 68 active LN patients were enrolled (mean age 31.7 ± 10.0 years, median UPCR 4.8 g/g creatinine level with interquartile range (IQR) 2.5 to 6.9 and mean estimated glomerular filtration rate (GFR) 89.6 ± 33.7 mL/min/1.73 m). At baseline measurement, median urinary NGAL in complete response, partial response and nonresponse groups was 10.86 (IQR; 6.16, 22.4), 19.91 (IQR; 9.05, 41.91) and 65.5 (IQR; 18.3, 103) ng/mL, respectively (p = 0.006). Urinary NGAL (ng/mL) correlated positively with proteinuria and blood pressure, and correlated negatively with serum complement C3 level and estimated GFR. Based on ROC analysis, urinary NGAL (AUC; 0.724, 95%CI 0.491-0.957) outperformed conventional biomarkers (serum creatinine, urine protein, and GFR) in differentiating complete and partial response groups from the nonresponse group. The urine NGAL cut-off value in the ROC curve, 28.08 ng/mL, discriminated nonresponse with 72.7% sensitivity and 68.4% specificity.

Conclusion: Urine NGAL at baseline performed better than conventional markers in predicting a clinical response to treatment of active LN except serum complement C3 level. It may have the potential to predict poor response after induction therapy.
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http://dx.doi.org/10.1186/s12882-017-0678-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5545009PMC
August 2017

Nutritional status among peritoneal dialysis patients after oral supplement with ONCE dialyze formula.

Int J Nephrol Renovasc Dis 2017 13;10:145-151. Epub 2017 Jun 13.

Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok.

Background: Malnutrition is an important problem in patients treated with long-term dialysis, and most dialysis patients have lower dietary energy and protein intake. This study was undertaken to examine whether orally administered Otsuka Nutrition Pharmaceutical (ONCE) dialyze formula (ODF) supplement would improve energy intake without mineral and electrolyte disturbances in patients with continuous ambulatory peritoneal dialysis (CAPD).

Methods: The effects of ODF supplementation on nutrition markers including serum albumin and prealbumin concentrations and inflammatory stress in patients with chronic CAPD were evaluated. All patients received daily oral ODF supplements for 15 days. During follow-up, all patients were evaluated clinically and biochemically, and nutritional status was assessed.

Results: Thirty patients with mean age 61.9±12.3 years and weekly / 2.2±0.4 were studied. The mean values for nutritional parameters included a body weight of 53.7±9.5 kg, a serum albumin level of 3.3±0.4 g/dL, a serum prealbumin level of 33.8±11.1 mg/dL, a dietary energy intake of 21.9±7.1 kcal/kg/day, and a dietary protein intake of 0.9±0.3 g/kg/day. After 15-day ODF treatment, these patients had significant dietary energy and protein, carbohydrate, fat, fiber, potassium, calcium, and magnesium intake from baseline (<0.05). Furthermore, significant improvements were found in nutritional markers including body weight, blood urea nitrogen, and prealbumin levels, but no changes were observed in serum albumin and high-sensitivity C-reactive protein levels. At the end of follow-up, the frequency of patients with moderate malnutrition decreased from 24.2% to 18.2%, and no increased incidence was observed of hyperkalemia, hyperphosphatemia, and metabolic acidosis.

Conclusion: ODF supplementation ameliorates low dietary energy and nutrient intake as well as improves serum prealbumin and body weight in patients with long-term CAPD.
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http://dx.doi.org/10.2147/IJNRD.S138047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5476629PMC
June 2017

Long-term (52-week) safety and efficacy of Sacubitril/valsartan in Asian patients with hypertension.

Hypertens Res 2017 May 17;40(5):472-476. Epub 2016 Nov 17.

Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.

Sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor-neprilysin inhibitor, demonstrated significant reductions in office and 24 h ambulatory blood pressure (BP) over 8 weeks in Asian patients with hypertension. This 52-week extension to the 8-week core study was aimed at evaluating the long-term safety, tolerability and efficacy of sacubitril/valsartan. Patients who completed an 8-week randomized study (the core study) were enrolled in this 52-week open-label study and received sacubitril/valsartan 200 mg QD. The sacubitril/valsartan dose was uptitrated to 400 mg QD if BP was uncontrolled (>140/90 mm Hg) after 4 weeks. Subsequently, in patients with uncontrolled BP, treatment was intensified every 4 weeks with amlodipine 5-10 mg followed by hydrochlorothiazide 6.25-25 mg. Of the 341 patients enrolled, 7 (2.1%) discontinued the study drug due to adverse events (AEs). The incidence of AEs and serious AEs were 63.9 and 3.8%, respectively, and no deaths were reported in this study. The most frequent AEs were nasopharyngitis (18.2%) and dizziness (8.8%). Events that were potentially indicative of low BP were infrequent. One patient reported mild transient angioedema (lasting 2.5 h) that resolved without treatment but led to study drug discontinuation. The sacubitril/valsartan-based regimen provided clinically significant mean sitting systolic BP (msSBP) and mean sitting diastolic BP (msDBP) reductions from baseline (-24.7/-16.2 mm Hg). The overall BP control, msSBP and msDBP response rates were 75.3, 90.6 and 87.6%, respectively. Long-term use of sacubitril/valsartan was generally safe and well-tolerated in patients with hypertension and provided significant BP reductions from baseline.
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http://dx.doi.org/10.1038/hr.2016.151DOI Listing
May 2017

Novel Tubular Biomarkers Predict Renal Progression in Type 2 Diabetes Mellitus: A Prospective Cohort Study.

J Diabetes Res 2016;2016:3102962. Epub 2016 Sep 8.

Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand.

Tubulointerstitial injury is both a key feature of diabetic nephropathy and an important predictor of renal dysfunction. Novel tubular biomarkers related to renal injury in diabetic nephropathy could improve risk stratification and prediction. A total of 303 type 2 diabetic patients were followed up. The baseline urine values of cystatin-C to creatinine ratio (UCCR), angiotensinogen to creatinine ratio (UANG), NGAL to creatinine ratio (UNGAL), and KIM-1 to creatinine ratio (UKIM-1) were measured. The primary outcome was a decline in estimated GFR of ≥25% yearly from baseline. Urine tubular biomarkers of UCCR, UANG, UNGAL, and UKIM-1 were significantly higher according to the degree of albuminuria and all were significantly higher among patients with rapid decline in estimated GFR of ≥25% yearly from baseline. All biomarkers predicted primary outcomes with ROC for UCCR of 0.72; 95% CI 0.64-0.79, for UANG of 0.71; 95% CI 0.63-0.79, for UNGAL of 0.64; 95% CI 0.56-0.72, and for UKIM-1 of 0.71; 95% CI 0.63-0.79. Using multivariate Cox regression analysis, the number of patients with rapid renal progression was higher among those in the upper quartiles of all biomarkers than in those in the lower quartiles. . Type 2 diabetic patients with high levels of urine tubular biomarkers had a more rapid decline in renal function.
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http://dx.doi.org/10.1155/2016/3102962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5031837PMC
September 2016

Electrolyte disturbances and risk factors of acute kidney injury patients receiving dialysis in exertional heat stroke.

BMC Nephrol 2016 06 6;17(1):55. Epub 2016 Jun 6.

Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, 315, Bangkok, 10400, Thailand.

Background: Exertional heat stroke (EHS) is a life-threatening illness and leads to multi-organ dysfunction including acute kidney injury (AKI). The clinical significance of abnormal electrolytes and renal outcomes in ESH patients has been poorly documented. We aim to exhibit the electrolyte abnormalities, renal outcomes and risk factors of patients with AKI receiving dialysis in EHS.

Methods: A retrospective cohort study in EHS patients between 2003 and 2014 were conducted. Clinical and laboratory outcomes including serum and urine electrolytes, AKI and dialysis were assessed on admission, during hospitalization and at the time of their discharge from the hospital. A logistic regression analysis was performed for risk factors of acute dialysis.

Results: All 66 subjects with mean age 22.1 ± 4.3 years were included. On admission, the common electrolyte disturbances were hypokalemia (71.2 %), hypophosphatemia (59.1 %), hyponatremia (53.0 %), hypocalcemia (51.5 %), and hypomagnesemia (34.9 %). Electrolytes depletion was confirmed as renal loss (potassium loss; 54.2 %, phosphate loss; 86.7 %, sodium loss; 64.7 % and magnesium loss; 83.3 %). During hospitalization ranging from 2 to 209 days, 90.9 % patients suffered from AKI with 16.7 % receiving acute dialysis, and 3 % patients died. At discharge, AKI and electrolyte abnormalities had dramatically improved. The prognosis factors for AKI receiving dialysis were identified as neurological status, renal function and serum muscle enzyme at time of admission.

Conclusion: The study suggests that hypoelectrolytemia and AKI are frequently observed in patients with EHS. Neurological impairment, impaired renal function, and increased serum muscle enzyme should be considered risk factors of acute dialysis.
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http://dx.doi.org/10.1186/s12882-016-0268-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4895821PMC
June 2016

The effect of ONCE Renal on minerals and electrolytes in predialysis patients with chronic kidney disease.

Int J Nephrol Renovasc Dis 2016 5;9:81-6. Epub 2016 Apr 5.

Division of Nephrology, Department of Medicine, Phramongkutklao College of Medicine, Bangkok, Thailand.

Background: Malnutrition is one common adverse consequence in patients with advanced chronic kidney disease (CKD), and most patients have a lower-than-normal dietary energy intake. The present study was undertaken to examine whether orally administered ONCE Renal formula (ORF) supplement would improve energy intake without minerals and electrolytes disturbances in predialysis patients with CKD.

Methods: All eligible nondiabetic patients with CKD received ORF supplement for 1 week. Nutrition markers, renal function, and minerals and electrolytes were evaluated before and after supplementing. All patients kept a 3-day food record and were interviewed by a registered dietitian.

Results: A total of 29 patients with mean age 64.9±13.3 years were included. Mean estimated glomerular filtration rate was 37.7±12.1 mL/min/1.73 m(2). A significant increase was observed in amount of energy, fat, fiber, calcium, and magnesium intake after 1 week of ORF supplement. Moreover, in comparison with baseline values, the patients displayed decreased dietary protein intake and blood urea nitrogen and increased serum magnesium. However, no significant change was found in renal function, nutritional markers (body weight, prealbumin, albumin, and protein equivalence of total nitrogen appearance), serum calcium, phosphorus, sodium, potassium, and bicarbonate.

Conclusion: In patients with CKD, ingestion of ORF was well tolerated and had a positive effect with an increase in dietary energy, fat, and fiber intake, as well as a decreased dietary protein intake. No mineral or electrolyte abnormalities were observed during the study.
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http://dx.doi.org/10.2147/IJNRD.S98179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4827907PMC
April 2016

Combination of Escitalopram and Rasagiline Induced Serotonin Syndrome: A Case Report and Review Literature.

J Med Assoc Thai 2015 Dec;98(12):1254-7

Background: Serotonin syndrome is a rare but potentially fatal complication of drugs that have effects on central nervous system serotonin. It is characterized by sudden onset of altered mental status, increased neuromuscular activity, and autonomic instability.

Case Report: The authors reported a case of serotonin syndrome associated with combined therapy of monoamine oxidase-B inhibitors and selective serotonin reuptake inhibitor A 77-year-old Thai man had been taking escitalopram for depression for three years. He presented with high-grade fever and confusion two days after taking rasagiline for Parkinson's disease. He also had agitation, hallucination, and behavioral change. Escitalopram and rasagiline were discontinued but his renal function worsened, turning to acute kidney injury. He was diagnosed as serotonin syndrome.

Conclusion: This is the first case report of serotonin syndrome due to combination of escitalopram and rasagiline used.
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December 2015
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