Publications by authors named "Bancha Satirapoj"

72 Publications

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 Jan 16. 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
January 2021

Urine albumin dipstick independently predicts cardiovascular and renal outcomes among rural Thai population: a 14-year retrospective cohort study.

BMC Nephrol 2021 01 8;22(1):18. Epub 2021 Jan 8.

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

Background: Albuminuria is an established risk marker for both cardiovascular and renal outcomes. In this study, we expected to use portable and inexpensive test strips to detect urine albumin level for risk stratification in cardiovascular and renal outcomes among rural Thai community.

Objective: To evaluate the relationship between urine albumin dipstick and cardiovascular and renal complications in rural Thai population.

Methods: We conducted a retrospective study in 635 rural Thai adults who tested urine albuminuria by using commercial urine albumin dipstick and the Micral-albumin test II strips at baseline. The subjects were divided into normoalbuminuria (albumin < 20 mg/L), microalbuminuria (albumin 20-200 mg/L), or macroalbuminuria (Urine dipstick at least 1+ or albumin > 200 mg/L). We collected data on the incidences of primary composite outcomes including cardiovascular or renal morbidity and mortality. Incident density and cox regression were analyzed to evaluate the association between albuminuria status and primary composite outcome.

Results: During an average 14-year follow-up, 102 primary composite events occurred including 59 (13.1%), 32 (20.6%) and 11 (39.3%) among 452, 155, and 28 subjects with normoalbuminuria, microalbuminuria, and macroalbuminuria, respectively. Incident densities of primary composite outcome were elevated continually according to the degree of albuminuria (9.36, 17.11 and 38.12 per 1000 person-years). Compared with the subjects without albuminuria, subjects with microalbuminuria and macroalbuminuria at baseline had higher risk for primary composite outcome in univariate model. After multivariate analysis was performed, the effect of macroalbuminuria was only persisted with 3.13-fold risk (adjusted HR 3.13; 95% CI 1.40-6.96, P= 0.005).

Conclusion: Albuminuria from semi-quantitative methods is an important factor predicting cardiovascular and renal risk among subjects in Thai rural population. Our findings support to also incorporating urine albumin dipstick into assessments of cardiovascular risk in the general population.
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http://dx.doi.org/10.1186/s12882-020-02215-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791992PMC
January 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
August 2020

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
August 2020

Ultrafiltration rates and intradialytic hypotension: A case-control sampling of pooled haemodialysis data.

J Ren Care 2021 Mar 30;47(1):34-42. Epub 2020 Jul 30.

Department of Medicine, Nephrology division, Faculty of Medicine, Thammasat University, Khlong Luang, Thailand.

Background: Intradialytic hypotension (IDH) is one of the most critical adverse events during maintenance haemodialysis. Previous studies reported the association of fluid removal rate with the occurrence of IDH.

Objective: We aimed to identify the optimal threshold of ultrafiltration rate to prevent the occurrence of IDH events. DESIGN, PARTICIPANTS AND MEASUREMENTS: Prognostic factor research with a retrospective case-control design was conducted. Patient data were gathered from four haemodialysis units from January to December 2017. All the haemodialysis records were independently justified, whether IDH occurred or not, based on the standard definition. A total of 10 haemodialysis sessions were sampled from each patient's pool based on the incidence of events. The association of ultrafiltration rates and IDH events was explored by multivariable multilevel logistic regression.

Results: A total of 1080 haemodialysis sessions from 108 patients were included: 149 (13.8%) with IDH and 931 (86.2%) without IDH. After adjusting for all pre-specified risk factors and imbalance baselines, the odds ratio of IDH were 1.22 (95% confidence interval [CI]: 0.59, 2.52) for rate 10-12 ml/kg/h; 2.52 (95% CI: 1.20, 5.29) for rate 12-14 ml/kg/h; 4.02 (95% CI: 1.61, 10.03) for rate 14-16 ml/kg/h; and 7.41 (95% CI: 2.53, 21.68) for rate >16 ml/kg/h comparing to the referent rate of <10 ml/kg/h.

Conclusion: The ultrafiltration rate should be limited to 12 ml/kg/h. If a higher rate of fluid removal was indicated, it should not exceed 16 ml/kg/h to avoid the occurrence of IDH.
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http://dx.doi.org/10.1111/jorc.12340DOI Listing
March 2021

Real-world Evaluation of glycemic control and hypoglycemic Events among type 2 Diabetes mellitus study (REEDS): a multicentre, cross-sectional study in Thailand.

BMJ Open 2020 02 12;10(2):e031612. Epub 2020 Feb 12.

Department of Medicine, Faculty of Medicine Siriraj Hospital Mahidol University, Bangkok, Thailand.

Objective: Patients with type 2 diabetes mellitus (T2DM) often experience hypoglycaemia and weight gain due to treatment side effects. Sulfonylureas (SU) and the combination of SU and metformin (SU+MET) were the most common monotherapy and combination therapies used in Thailand tertiary care hospitals. This study aimed to assess the glycaemic goal attainment rates, hypoglycaemic episodes, weight gain and treatment compliance among patients with T2DM receiving SU or SU+MET.

Research Design And Methods: A multicentre cross-sectional survey and retrospective review was conducted in five tertiary care hospitals, Thailand. Patients with T2DM aged ≥30 years were included consecutively during a 12-month period. Glycaemic control, experiences of hypoglycaemia, weight gain and compliance were evaluated. Glycaemic goal attainment was defined by HbA level less than 7%.

Results: Out of the 659 patients (mean age (±SD)), 65.5 (10.0) years and median duration of T2DM (IQR), 10 (5-15) years), 313 (47.5%) achieved the glycaemic goal. HbA levels in the patients with goal attainment was significantly lower compared with those without (6.3%±0.5% vs 8.1%±1.2%, p<0.001). Goal attainment was significantly lower among patients treated with SU+MET than those treated with SU alone (43.5% vs 63.0%; OR 0.45, 95% CI 0.31, 0.66, p<0.001). A third of patients reported experiencing hypoglycaemia (30.7%) and weight gain (35.4%). Weight gain in the SU+MET group was lower than those receiving SU alone (33.1% vs 44.6%, p=0.015), but there was no difference in hypoglycaemic events. Major events in the previous 12 months were experienced by 68 patients, most commonly congestive heart failure and ischaemic heart disease. Approximately half of the patients (52.2%) reported not always taking their medication as prescribed.

Conclusions: Among patients with T2DM receiving SU or SU+MET, only about half of the patients achieved glycaemic goal and compliance with the treatment. Hypoglycaemia and weight gain posed a significant burden with risk of weight gain higher in the SU group.
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http://dx.doi.org/10.1136/bmjopen-2019-031612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7045111PMC
February 2020

Rate of kidney function decline and factors predicting progression of kidney disease in type 2 diabetes mellitus patients with reduced kidney function: A nationwide retrospective cohort study.

Ther Apher Dial 2020 Dec 6;24(6):677-687. Epub 2020 Mar 6.

Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi.

Currently, the data on independent risk factors for the progression of kidney disease in type 2 diabetes mellitus (T2DM) patients with CKD are limited. This study aimed to investigate CKD progression in T2DM patients who have reduced kidney function with baseline estimated glomerular filtration rate (eGFRs) between 15 and 59 mL/min/1.73 m . This study was composed of a nationwide retrospective cohort of adult T2DM patients from 831 public hospitals in Thailand during the year 2015. T2DM patients with CKD stages 3 and 4 were followed up, until development of CKD stage 5, requirement of chronic dialysis, loss to follow-up, death, or 31 May 2018, whichever came first. Cox proportional hazard regression was utilized for analysis. A total of 8464 participants were included; 30.4% were male. The mean age was 69 ± 10 years. The mean eGFR was 45 ± 11 mL/min/1.73 m . The incidence of CKD stage 5 or the need for chronic dialysis was 16.4 per 1000 person-years. The annual rate of eGFR decline during a mean follow-up of 29 months was -2.3 mL/min/1.73 m ; 14.4% had a rapid decline in eGFR. The risk factors associated with progression to CKD stage 5 or the need for chronic dialysis were diabetes duration, systolic blood pressure, serum uric acid, albuminuria, and baseline eGFR. Conversely, older age and the use of renin-angiotensin aldosterone system blockade were associated with decreased risks for rapid CKD progression and incidence CKD stage 5 or dialysis. This study identifies multiple predictive risk factors that support a multifaceted approach to prevent progression of advanced CKD.
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http://dx.doi.org/10.1111/1744-9987.13480DOI Listing
December 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

Impact of Hypoglycemia on Health-Related Quality of Life among Type 2 Diabetes: A Cross-Sectional Study in Thailand.

J Diabetes Res 2019 23;2019:5903820. Epub 2019 Oct 23.

Department of Medicine, Siriraj Hospital, Bangkok, Thailand.

Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases. Patients are generally advised lifestyle changes with antihyperglycemic agents prescribed. The major drawback of prescribing antihyperglycemic agents is the risk of hypoglycemia which subsequently impacts on health-related quality of life (HRQoL). This study is aimed at examining association between previous history of hypoglycemia and HRQoL. The study was a multicenter cross-sectional study, conducted from February 2013 to March 2015 at 5 tertiary care hospitals in Thailand (Srinagarind, Phramongkutklao, Ramathibodi, King Chulalongkorn Memorial, and Siriraj hospitals). The study population were males or females diagnosed with type 2 DM according to ADA criteria, 30 years of age or older, who had been treated with sulfonylurea (SU) monotherapy or SU and metformin combination for at least 6 months. Prespecified medical factors were extracted from medical records 12 months prior to patients' enrolment. The experience of hypoglycemia questionnaire was used to collect and measure severity of hypoglycemia experienced during the previous 6 months. HRQoL was assessed using the 3-level version of EuroQol-5-dimension (EQ-5D-3L) and visual analogue scale (EQ-VAS) questionnaires. Of 659 eligible patients surveyed, 202 patients (30.65%) had experienced symptoms of hypoglycemia. HRQoL was significantly lower among patients reporting at least one of hypoglycemic symptoms, measured by EQ-VAS scores (mean ± SD; 73.66 ± 13.18, 73.56 ± 15.10, or 68.93 ± 14.76 vs. 77.01 ± 13.02, one-way ANOVA; = 0.006) and EQ-5D-3L index scores (0.62 ± 0.47, 0.68 ± 0.38, or 0.58 ± 0.51 vs. 0.79 ± 0.31, one-way ANOVA; < 0.001) for mild, moderate, or severe/very severe hypoglycemic patients compared with patients without hypoglycemic symptoms. After adjusting for confounding factors in a multiple linear regression model, patients with hypoglycemic symptoms either mild, moderate, or severe/very severe demonstrated significantly higher impairment for EQ-VAS and EQ-5D indexes than those who did not experience hypoglycemic symptoms. In conclusion, our study showed decreased HRQoL determined by EQ-5D and EQ-VAS in patients reporting symptoms of hypoglycemia compared with patients not reporting hypoglycemic symptoms, relative to severity of hypoglycemia.
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http://dx.doi.org/10.1155/2019/5903820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854960PMC
April 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

Cardiovascular and Renal Outcomes in an Excellent Chronic Kidney Disease Clinic Compared with an Outpatient Clinic in a Primary Care Setting: A Retrospective Cohort Study.

Kidney Dis (Basel) 2019 Jun 3;5(3):144-152. Epub 2019 Jan 3.

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

Background: Chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality. In standard care, the physician attempts to control all known risk factors, but treatment goals are achieved with difficulty. Assistance by a multidisciplinary care team may improve outcomes.

Objective: To compare the cardiovascular and renal endpoints between patients with CKD receiving care from excellent CKD and outpatient clinics.

Methods: A retrospective cohort study was conducted in a primary care setting in Thailand. Patients with CKD stages 3 and 4 in excellent CKD ( = 96) and outpatient clinics ( = 192) were matched in a 1: 2 ratio with the propensity score. We collected data from electronic medical records concerning the incidences of primary composite outcomes including rapid renal progression, end-stage renal disease, myocardial infarction, congestive heart failure, stroke, and mortality. Multidisciplinary team care in the excellent CKD clinic consisted of physician, nurse, pharmacist, dietitian, physical therapist, and applied Thai traditional physician. The outpatient clinic consisted of physician care only.

Results: Subjects' mean age was 64.54 ± 10.96 years, and 52.1% were female. During an average 49.63 ± 8.36 months of follow-up, 74 events occurred including 35 (47.30%) patients who experienced renal events, 29 (39.19%) who experienced cardiovascular events, and 10 (13.51%) who experienced loss of life. The Kaplan-Meier curve indicated a higher percentage of subjects without primary composite outcomes in the excellent CKD clinic than those in the outpatient clinic (66.85%; 95% CI 0.48-0.80 vs. 44.71%; 95% CI 0.29-0.60; = 0.005). From multivariate analysis, the excellent CKD clinic group had a 64% lower risk for primary composite outcomes compared with those in the outpatient clinic (adjusted HR 0.36; 95% CI 0.18-0.74; = 0.005).

Conclusion: A multidisciplinary care system can reduce composition outcomes including cardiovascular and renal outcomes for the growing CKD population. The optimal outcomes arise from the medical personnel's teamwork, not from one physician alone.
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http://dx.doi.org/10.1159/000495464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587207PMC
June 2019

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

The association between renal function and neurological diseases in type 2 diabetes: a multicenter nationwide cross-sectional study.

Hosp Pract (1995) 2019 Feb 25;47(1):46-52. Epub 2018 Nov 25.

d Division of Nephrology, Department of Medicine , University of Mississippi Medical Center , Jackson , MS , USA.

Background: The evidence for an association between renal function and neurological diseases among type 2 diabetes mellitus (T2DM) patients, particularly in the Asian population, is limited. This study aimed to assess the association between glomerular filtration rate (GFR) and various neurological diseases among T2DM patients in Thailand using a nationwide patient sample.

Methods: We conducted a nationwide cross-sectional study based on the DM/HT study of the Medical Research Network of the Consortium of Thai Medical Schools. This study evaluated adult T2DM patients receiving care at public Thailand hospitals in the year 2014. GFR was categorized into ≥60, 30-59, and < 30 mL/min/1.73 m. Neurological diseases studied included ischemic stroke/transient ischemic attack (TIA), hemorrhagic stroke, dementia, all cerebrovascular disease, and peripheral neuropathy. Multivariate logistic regression was performed to assess the association between GFR and neurological diseases.

Results: A total of 30,423 T2DM patients with available GFR data were included in the analysis. The mean GFR was 68.18 ± 26.45 mL/min/1.73 m. The prevalence of ischemic stroke/TIA, hemorrhagic stroke, dementia, any cerebrovascular diseases and peripheral neuropathy were 2.9%, 0.3%, 0.1%, 3.2%, and 3.1%, respectively. Patients with GFR of 30-59 and <30 mL/min/1.73 m were significantly associated with increased rates of ischemic stroke/TIA, any cerebrovascular diseases, and peripheral neuropathy when compared with patients with GFR of ≥60 mL/min/1.73 m. This association remained significant after adjustment for potential confounders.

Conclusion: Decreased GFR was associated with increased ischemic stroke/TIA, all cerebrovascular diseases, and peripheral neuropathy. GFR should be monitored in diabetic patients for neurological disease awareness and prevention.
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http://dx.doi.org/10.1080/21548331.2019.1549916DOI Listing
February 2019

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

Urinary epidermal growth factor, monocyte chemoattractant protein-1 or their ratio as predictors for rapid loss of renal function in type 2 diabetic patients with diabetic kidney disease.

BMC Nephrol 2018 09 21;19(1):246. Epub 2018 Sep 21.

Division of Nephrology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama 6 Rd, Bangkok, 10400, Thailand.

Background: Increased monocyte chemoattractant protein-1 (MCP-1) and decreased epidermal growth factor (EGF) are promising biomarkers to predict progressive decline in kidney function in non-diabetic kidney diseases. We aimed to evaluate the performance of urinary EGF, MCP-1 or their ratio in predicting rapid decline of GFR in a cohort of Type 2 diabetic patients (T2DM) with diabetic kidney disease (DKD).

Methods: T2DM patients (n = 83) with DKD at high risk for renal progression were followed up prospectively. The baseline urine values of MCP-1 to creatinine ratio (UMCP-1), EGF to creatinine ratio (UEGF), EGF to MCP-1 ratio (UEGF/MCP-1) and albumin to creatinine ratio (UACR) were measured. The primary outcome was a decline in estimated glomerular filtration rate (GFR) of ≥25% yearly from baseline.

Results: During follow-up time of 23 months, patients with rapid decline in estimated GFR of ≥25% yearly from baseline had significantly higher baseline levels of UMCP-1, and UACR and lower UEGF and UEGF/MCP-1 ratio. All renal biomarkers predicted primary outcomes with ROC (95%CI) for UMCP-1=0.73 (0.62-0.84), UEGF=0.68 (0.57-0.80), UEGF/MCP-1=0.74 (0.63-0.85), and UACR =0.84 (0.75-0.93). By univariate analysis, blood pressure, GFR, UACR, UMCP-1, UEGF, and UEGF/MCP-1 were associated with rapid decline GFR. By multivariate analysis, UACR, systolic blood pressure, and UMCP-1 or UEGF/MCP-1 were independently associated with rapid GFR decline.

Conclusions: UMCP-1 or UEGF/MCP-1 ratio were associated with rapid renal progression independent from conventional risk factors in DKD.
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http://dx.doi.org/10.1186/s12882-018-1043-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150979PMC
September 2018

Tubulointerstitial Biomarkers for Diabetic Nephropathy.

Authors:
Bancha Satirapoj

J Diabetes Res 2018 8;2018:2852398. Epub 2018 Feb 8.

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

Patients with diabetic nephropathy have a higher risk of mortality, mostly from cardiovascular complications. Standard biomarkers including serum creatinine, estimated glomerular filtration rate, and albuminuria are imprecise, do not directly measure renal tissue injury, and are relatively insensitive to small changes in renal function. Thus, availability of novel biomarkers that are sensitive, specific, and precise as well as able to detect kidney injury and predict clinically significant outcomes would be widely useful in diabetic nephropathy. Novel biomarkers of the processes that induce tubulointerstitial changes may ultimately prove to better predict renal progression and prognosis in type 2 diabetes. Recently, certain biomarkers, which were initially identified in acute kidney injury, also have been reported to confer value in evaluating patients with chronic kidney disease. Biomarkers such as cystatin C, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), angiotensinogen, periostin, and monocyte chemoattractant protein-1 (MCP-1) reflect tubular injury. In this article, we focused on the potential applications of these biomarkers in diabetic nephropathy.
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http://dx.doi.org/10.1155/2018/2852398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5822931PMC
October 2018

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

Sodium-Glucose Cotransporter 2 Inhibitors with Renoprotective Effects.

Authors:
Bancha Satirapoj

Kidney Dis (Basel) 2017 Jul 8;3(1):24-32. Epub 2017 Apr 8.

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

Background: Diabetes is the leading cause of end-stage renal disease (ESRD) and accounts for 40-50% of patients requiring renal replacement therapy. The main pathophysiology of diabetic nephropathy comprises glucose-dependent pathways, hemodynamic pathways, and genetic factors.

Summary: Glucose-dependent pathways, known as advanced glycation, polyols, and protein kinase C activation have been implicated in the pathogenesis of diabetic nephropathy. Current studies have indicated that intensified glycemic control retards the rate of development of albuminuria and impairs renal function in both patients with type 1 and 2 diabetes. However, therapeutic options have substantially increased over the last decade, but have not yet been translated to remarkably reduce the incidence of ESRD from diabetic nephropathy. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class of glucose-lowering agents with potential renoprotective effects.

Key Message: SGLT2 inhibitors represent a promising therapeutic approach to prevent and improve nephropathy among patients with type 2 diabetes. The current data strongly support that SGLT2 inhibitors have renoprotective properties not only by improving glycemic control but also through hemodynamic and nonhemodynamic renal effects. This review focuses on the latest published data dealing with hypoglycemic agents and SGLT2 inhibitors regarding the progression of kidney disease.
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http://dx.doi.org/10.1159/000471765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5527177PMC
July 2017

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

Beta Cell Function and Insulin Resistance After Conversion from Tacrolimus Twice-Daily to Extended-Release Tacrolimus Once-Daily in Stable Renal Transplant Recipients.

Ann Transplant 2016 Dec 16;21:765-774. Epub 2016 Dec 16.

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

BACKGROUND Post-transplantation diabetes mellitus is a major metabolic adverse effect of tacrolimus (TAC). The objective of this study was to determine if the conversion from tacrolimus twice-daily (TAC-BID) to extended-release tacrolimus once-daily (TAC-OD) in stable renal transplant recipients had any effect on beta cell function (HOMA-b), insulin resistance (HOMA-IR), patient preference, and expense. MATERIAL AND METHODS Twenty-eight renal transplant recipients were recruited and converted from TAC-BID to TAC-OD at the same dose. Primary outcomes were beta cell function and insulin resistance in stable renal transplant recipients at 4, 8, and 16 weeks after conversion. Secondary outcomes were patient satisfaction and expense of medication. RESULTS No significant change in the HOMA-β and HOMA-IR was found in any of the 28 renal transplant recipients. However, HOMA-β increased from 60 (37.33, 109.71) to 78.5 (44.3, 108.4) (p=0.02) in 15 patients who had the conversion within 4 years after renal transplantation. In multivariate regression analysis, the conversion from TAC-BID to TAC-OD significantly increased HOMA-b at 4 months at 1.21 mIU/mmol (95%CI 0.54-1.88 mIU/mmol, p=0.01) in this subgroup. The renal transplant recipients reported the conversion was more satisfactory and cost of treatment was comparable. CONCLUSIONS In short-term follow-up, conversion from TAC-BID to TAC-OD is safe in stable renal transplant recipients and might be beneficial in term of improved beta cell function in the early years after renal transplantation. The conversion caused comparable cost and was preferred by renal transplant recipients.
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http://dx.doi.org/10.12659/aot.900638DOI Listing
December 2016

Selective cyclooxygenase-2 inhibitor use and progression of renal function in patients with chronic kidney disease: a single-center retrospective cohort study.

Int J Nephrol Renovasc Dis 2016 7;9:273-278. Epub 2016 Nov 7.

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

Background: The use of selective COX-2 (sCOX-2) inhibitors with acute kidney injury, salt water retention, and cardiovascular events have been correlated in subjects with normal kidney function, but sCOX-2 inhibitor use concerning the progression of chronic kidney disease (CKD) remains uncertain.

Objectives: To determine the progression of renal function and electrolyte abnormalities among CKD patients after using sCOX-2 inhibitors during short- and long-term periods.

Methods: The study employed a retrospective cohort design comprising all types of CKD patients with and without sCOX-2 inhibitors (celecoxib and etoricoxib). Data collected included medical data, estimated glomerular filtration rate (eGFR), and serum electrolytes at 3 and 6 months between January 2009 and January 2014. Subjects attended the outpatient clinic and were then followed up until discontinuation of the drugs at years 1 and 2 until May 2016.

Results: Ninety-two CKD patients on sCOX-2 inhibitors and 92 CKD patients without sCOX-2 inhibitors were included. The sCOX-2 inhibitor group showed more decline in eGFR than the control group at 3 and 6 months of follow-up (-8.27±9.75 vs -1.64±6.05 mL/min/1.73 m, <0.001 and -12.36±6.48 vs -4.31±5.11 mL/min/1.73 m, =0.001, respectively) and at 1 and 2 years of follow-up after subjects discontinued sCOX-2 (-6.84±10.34 vs -1.61±8.93 mL/min/1.73 m, =0.004 and -10.26±10.19 vs -5.12±8.61 mL/min/1.73 m, =0.005, respectively). In addition, the sCOX-2 inhibitor group had significantly more increased serum potassium during the study follow-up than the control group.

Conclusion: The sCOX-2 inhibitors are associated with an increased risk for rapid eGFR decline and hyperkalemia in both the short term and in the long term after sCOX-2 inhibitors were terminated in the setting of a community-based CKD population. For CKD patients, these results suggest that sCOX-2 inhibitors should be closely monitored and chronic exposure to any sCOX-2 inhibitors should be avoided.
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http://dx.doi.org/10.2147/IJNRD.S121698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5106237PMC
November 2016

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