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1.
Clin Exp Nephrol ; 26(12): 1180-1193, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35999302

RESUMO

BACKGROUND: Decline of estimated glomerular filtration rate (eGFR) is associated with increased cardiovascular (CV) morbidity and mortality, but the predictive value of different eGFR on CV outcomes is limited in Southeast Asian populations. AIMS: We aimed to stratify CV outcomes according to renal function among Thai patients with high atherosclerosis risk. METHODS: We performed a secondary analysis in a 5-year national cohort entitled "CORE-Thailand study." Subjects were classified in 6 groups according to baseline kidney function: group I, eGFR ≥ 90; group II, eGFR 60-89; group IIIa, eGFR 45-59; group IIIb, eGFR 30-44; group IV, eGFR 15-29; group V, eGFR < 15 ml/min/1.73 m2 or receiving renal replacement therapy. The primary outcome was 4-point major adverse cardiovascular events (MACE). Secondary outcomes included all-cause mortality, CV mortality, hospitalization for heart failure, nonfatal myocardial infarction, and nonfatal stroke. RESULTS: A total of 6376 subjects (3467 men and 2909 women) were categorized in 6 groups. After adjusting covariates in the Cox proportional hazards model, compared to group I, subjects in groups II-V had a 1.65-fold, 2.17-fold, 2.67-fold, 4.24-fold, and 4.87-fold risk for 4-point MACE, respectively, with statistical significance at P < 0.05 in all groups. Kaplan-Meier analysis illustrated stepwise lower survivals from 4-point MACE following the groups with lower baseline eGFR (log-rank test with P < 0.001). All secondary outcomes showed similar trends as the primary outcome, except nonfatal stroke. CONCLUSION: Lower baseline kidney function was independently associated with increased risk of CV events and all-cause mortality in Thai populations at high CV risk.


Assuntos
Doenças Cardiovasculares , Sistema Cardiovascular , Acidente Vascular Cerebral , Masculino , Humanos , Feminino , Taxa de Filtração Glomerular , Tailândia/epidemiologia , Estudos de Coortes , Doenças Cardiovasculares/epidemiologia , Fatores de Risco
2.
Ther Apher Dial ; 26(2): 378-386, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34378863

RESUMO

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.


Assuntos
Interleucina-6 , Deficiência de Vitamina D , Suplementos Nutricionais , Método Duplo-Cego , Ergocalciferóis , Humanos , Diálise Renal/efeitos adversos , Vitamina D/análogos & derivados , Deficiência de Vitamina D/tratamento farmacológico , Deficiência de Vitamina D/etiologia
3.
Int Urol Nephrol ; 54(7): 1641-1652, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34724144

RESUMO

BACKGROUND: Low ankle-brachial index (ABI) related ischemic events are common among individuals with chronic kidney disease (CKD). It is also associated with an increased risk of rapid renal function decline. The presence of peripheral artery disease (PAD) with low ABI among patients with high cardiovascular (CV) risk increases limb loss and mortality. AIMS: To estimate the association between abnormal ABI and renal endpoints and all-cause mortality. METHODS: A multicenter prospective cohort study was conducted among subjects with high CV risk or established CV diseases in Thailand. The subjects were divided into 3 groups based on ABI at baseline > 1.3, 0.91-1.3, and ≤ 0.9, respectively. Primary composite outcome consisted of estimated glomerular filtration rate (eGFR) decline over 40%, eGFR less than 15 mL/min/1.73 m2, doubling of serum creatinine and initiation of dialysis. The secondary outcome was all-cause mortality. Cox regression analysis and Kaplan-Meier curve were performed. RESULTS: A total of 5543 subjects (3005 men and 2538 women) were included. Cox proportional hazards model showed a significant relationship of low ABI (ABI ≤ 0.9) and primary composite outcome and all-cause mortality. Compared with the normal ABI group (ABI 0.91-1.3), subjects with low ABI at baseline significantly had 1.42-fold (95% CI 1.02-1.97) and 2.03-fold (95% CI 1.32-3.13) risk for the primary composite outcome and all-cause mortality, respectively, after adjusting for variable factors. CONCLUSION: Our study suggested that PAD independently predicts the incidence of renal progression and all-cause mortality among Thai patients with high CV risk.


Assuntos
Doenças Cardiovasculares , Doença Arterial Periférica , Índice Tornozelo-Braço/efeitos adversos , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Rim/fisiologia , Masculino , Doença Arterial Periférica/complicações , Doença Arterial Periférica/diagnóstico , Estudos Prospectivos , Fatores de Risco
4.
Clin Exp Nephrol ; 26(3): 247-256, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34643840

RESUMO

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 m2, 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.


Assuntos
Aterosclerose , Rigidez Vascular , Tornozelo/irrigação sanguínea , Índice Tornozelo-Braço , Aterosclerose/diagnóstico , Estudos de Coortes , Feminino , Humanos , Rim/fisiologia , Masculino , Estudos Prospectivos , Diálise Renal , Fatores de Risco , Tailândia/epidemiologia
5.
Int Urol Nephrol ; 53(7): 1391-1398, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33682052

RESUMO

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.


Assuntos
Terapia de Imunossupressão , Nefrite Lúpica/classificação , Nefrite Lúpica/patologia , Adolescente , Adulto , Feminino , Humanos , Nefrite Lúpica/terapia , Masculino , Valor Preditivo dos Testes , Prognóstico , Indução de Remissão , Sociedades Médicas , Adulto Jovem
6.
J Diabetes Complications ; 33(9): 675-681, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31227289

RESUMO

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.


Assuntos
Biomarcadores/urina , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/urina , Progressão da Doença , Falência Renal Crônica/urina , Túbulos Renais/fisiopatologia , Idoso , Albuminúria/fisiopatologia , Angiotensinogênio/urina , Estudos de Coortes , Cistatina C/urina , Diabetes Mellitus Tipo 2/urina , Nefropatias Diabéticas/fisiopatologia , Feminino , Taxa de Filtração Glomerular , Receptor Celular 1 do Vírus da Hepatite A/análise , Humanos , Lipocalina-2/urina , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade
7.
Clin Kidney J ; 12(3): 326-332, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31198224

RESUMO

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 (n = 28) or standard treatment (n = 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 (FEPO4) 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 FEPO4 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.

8.
BMC Nephrol ; 18(1): 263, 2017 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-28778196

RESUMO

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 m2). 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.


Assuntos
Quimioterapia de Indução/tendências , Lipocalina-2/urina , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/urina , Adulto , Biomarcadores/urina , Feminino , Seguimentos , Humanos , Nefrite Lúpica/diagnóstico , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , Adulto Jovem
9.
J Diabetes Res ; 2016: 3102962, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27672664

RESUMO

Background. 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. Methods. 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. Results. 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. Conclusions. Type 2 diabetic patients with high levels of urine tubular biomarkers had a more rapid decline in renal function.

10.
PLoS One ; 10(4): e0124055, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25884625

RESUMO

BACKGROUND: Improving the early detection of diabetic nephropathy remains a great challenge in disease management. Periostin is a marker of renal tubular injury and related to progressive kidney injury in animal models of chronic kidney disease. The clinical implications of urinary periostin activities in patients with type 2 diabetes have not been evaluated. METHODS: Urine samples were obtained from 30 healthy volunteers and 328 type 2 diabetic patients with normoalbuminuria (n=114), microalbuminuria (n=100) and macroalbuminuria (n=114). The excretion levels of urinary periostin were quantified with enzyme-linked immunosorbent assay. Immunohistochemical periostin expression was determined in kidney tissues from overt diabetic nephropathy. RESULTS: Increased periostin expression in glomeruli and tubular epithelium in diabetic renal pathology was observed. Urinary periostin levels were significantly elevated in the patients of the normoalbuminuria [3.06 (IQR: 1.12, 6.77) ng/mgCr], microalbuminuria [8.71 (IQR: 5.09, 19.29) ng/mgCr] and macroalbuminuria [13.58 (IQR: 3.99, 16.19) ng/mgCr] compared with healthy controls [1.15 (IQR: 0.60, 1.63) ng/mgCr] (P<0.01).Increased urine periostin level significantly correlated with aging, high albuminuria and decline of GFR. Urine periostin ELISA also demonstrated high performance for the diagnosis of established normoalbuminuric, microalbuminuric and macroalbuminuric type 2 diabetes (AUC 0.78 (95%CI, 0.71 to 0.86), 0.99 (95%CI, 0.98 to 1.00) and 0.95 (95%CI, 0.91 to 0.98), respectively). CONCLUSION: The study indicates that increased urine periostin levels can be detected in patients with type 2 diabetes before the onset of significant albuminuria. Urinary periostin is an associated renal derangement in patients with established diabetic nephropathy and it may be used as an early marker of diabetic renal injury.


Assuntos
Moléculas de Adesão Celular/urina , Diabetes Mellitus Tipo 2/urina , Nefropatias Diabéticas/urina , Adulto , Idoso , Albuminúria/etiologia , Albuminúria/patologia , Albuminúria/urina , Biomarcadores/análise , Biomarcadores/urina , Biópsia , Moléculas de Adesão Celular/análise , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/patologia , Diagnóstico Precoce , Ensaio de Imunoadsorção Enzimática , Transição Epitelial-Mesenquimal , Feminino , Humanos , Testes de Função Renal , Glomérulos Renais/química , Glomérulos Renais/patologia , Túbulos Renais/química , Túbulos Renais/patologia , Masculino , Pessoa de Meia-Idade , Estudos de Amostragem
11.
Int J Nephrol ; 2015: 857316, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25874130

RESUMO

A total of 244 patients with lupus nephritis (219 women (89.8%) with a female to male ratio of 9 : 1) were included in the study. Clinical and laboratory findings at renal biopsy are clinically valuable in identifying different renal classifications of lupus pathology, activity, and chronicity index. Patients with class IVG had significantly higher proportions of microscopic hematuria, proteinuria, hypertension, impaired renal function, anemia, hypoalbuminuria, and positive anti-DNA antibody. All of these findings correlated well with high activity index and chronicity index of lupus pathology. Considering these correlations may help to determine the clinicopathologic status of lupus patients.

12.
J Med Assoc Thai ; 98(12): 1155-61, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27004299

RESUMO

BACKGROUND: Hyperuricemia has been associated with increased risk of endothelial dysfunction, cardiovascular, and renal disease. Allopurinol is a potent xanthine oxidase inhibitor used in hyperuricemic patients. It has been shown to decrease cardiovascular disease and hypertension. However, studies have reported conflicting evidence on its effects on blood pressure (BP) and estimated glomerular filtration rate (GFR) in chronic kidney disease (CKD) patients. OBJECTIVE: To demonstrate the effect of allopurinol on BP and estimated GFR in CKD patients. MATERIAL AND METHOD: Patients with CKD stage II-III were screened for possible study enrollment. All patients received allopurinol 50 mg once daily for 12 weeks. The main outcomes were to observe the changes of BP and GFR after given treatment. RESULTS: Forty-four patients were eligible with mean age of 70.14 ± 8.50 years and mean estimated GFR of 43.22 ± 14.44 mL/ min/1.73 m². Serum uric acid decreased significantly from 8.11 ± 2.68 to 7.05 ± 2.38 mg/dL (p = 0.012) at the end of the study. Allopurinol had also statistically significant lower systolic BP (137.72 ± 14.72 to 131.34 ± 12.10 mmHg, p = 0.019) and diastolic BP (79.63 ± 11.56 to 75.43 ± 9.80 mmHg, p = 0.037) at 12 weeks when compared to baseline. There was significant increased in GFR after treatment (43.22 ± 14.44 vs. 45.34 ± 16.09, mL/min/1.73 m², p = 0.029). No serious adverse effects were noted in any of the treated subjects. Two patients (4.5%) in the treatment group had minor skin reaction. CONCLUSION: The study results confirmed that 12 weeks of allopurinol treatment affects the values of serum uric acid, BP and GFR in early stage of CKD patients who already received standard antihypertensive agents without any significant serious adverse effects.


Assuntos
Alopurinol , Pressão Sanguínea/efeitos dos fármacos , Hiperuricemia , Insuficiência Renal Crônica/complicações , Ácido Úrico/sangue , Idoso , Alopurinol/administração & dosagem , Alopurinol/farmacocinética , Disponibilidade Biológica , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/farmacocinética , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Hiperuricemia/tratamento farmacológico , Hiperuricemia/etiologia , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Estudos Prospectivos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Resultado do Tratamento
13.
Hypertension ; 63(4): 698-705, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24446062

RESUMO

LCZ696 (Japanese adopted name: sucabitril valsartan sodium hydrate), a first-in-class angiotensin receptor neprilysin inhibitor, concomitantly inhibits neprilysin and blocks angiotensin type 1 receptor. This randomized, double-blind, placebo-controlled study, the first in Asia for this drug, evaluated the dose-related efficacy and safety of LCZ696 in patients with hypertension using 24-hour ambulatory blood pressure (BP) monitoring. Asian patients aged ≥18 years (n=389) with hypertension were randomized to receive LCZ696 100 mg (n=100), 200 mg (n=101), 400 mg (n=96), or placebo (n=92) for 8 weeks. The primary end point was mean difference across the 3 single-dose pairwise comparisons of LCZ696 versus placebo in clinic diastolic BP after 8-week treatment. Key secondary efficacy variables included changes in clinic systolic BP and pulse pressure and changes in 24-hour, daytime, and nighttime ambulatory BPs and pulse pressure. Safety assessments included recording all adverse events and serious adverse events. A total of 362 patients completed the study. Reductions in clinic systolic BP, diastolic BP (P<0.0001), and pulse pressure (P<0.001) were significantly greater with all doses of LCZ696 than with placebo. There were also significant reductions in 24-hour, daytime, and nighttime ambulatory systolic BP, diastolic BP, and pulse pressure for all doses of LCZ696 compared with placebo (P<0.0001). LCZ696 was well tolerated, and no cases of angioedema were reported. In conclusion, LCZ696 is effective for the treatment of hypertension in Asian population and, in general, is safe and well tolerated. Clinical Trial Information- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01193101.


Assuntos
Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Povo Asiático , Hipertensão/tratamento farmacológico , Hipertensão/etnologia , Neprilisina/antagonistas & inibidores , Tetrazóis/uso terapêutico , Idoso , Aminobutiratos/efeitos adversos , Aminobutiratos/farmacologia , Angioedema/epidemiologia , Antagonistas de Receptores de Angiotensina/efeitos adversos , Antagonistas de Receptores de Angiotensina/farmacologia , Compostos de Bifenilo , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Monitorização Ambulatorial da Pressão Arterial , China , Relação Dose-Resposta a Droga , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Hipertensão/fisiopatologia , Incidência , Japão , Masculino , Pessoa de Meia-Idade , República da Coreia , Taiwan , Tetrazóis/efeitos adversos , Tetrazóis/farmacologia , Tailândia , Resultado do Tratamento , Valsartana
14.
Clin Exp Nephrol ; 18(1): 10-5, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23757048

RESUMO

Structural and functional peritoneal membrane changes are associated with long-term peritoneal dialysis. These changes can lead to ultrafiltration failure and peritoneal fibrosis, reducing the efficacy of the peritoneal membrane to remove waste and balance fluid and electrolytes. The loss of mesothelial cells from the basement membrane is one of the major characteristics in peritoneal membrane structural change. Thus, if the reduction of peritoneal mesothelial cell mass in peritoneal dialysis patients is monitored, signs of ultrafiltration failure and peritoneal fibrosis can be detected early. One of biomarkers that can be used to indicate the change in peritoneal mesothelial cell mass is CA125, which is produced by mesothelial cells. In this article, we review the measurement and clinical use of CA125 in peritoneal dialysate effluent. Additionally, we address the data and studies on the association between dialysate CA125 levels and factors related to ultrafiltration failure and peritoneal fibrosis, including the parameters used to monitor the functional status of the peritoneal membrane. Our review shows that dialysate CA125 can be used to evaluate the peritoneal membrane in noninfected patients to predict peritoneal fibrosis, and it can also be used as a biomarker of biocompatible dialysis solutions.


Assuntos
Antígeno Ca-125/metabolismo , Soluções para Diálise/uso terapêutico , Proteínas de Membrana/metabolismo , Diálise Peritoneal/efeitos adversos , Fibrose Peritoneal/etiologia , Peritônio/metabolismo , Biomarcadores/metabolismo , Soluções para Diálise/metabolismo , Humanos , Fibrose Peritoneal/diagnóstico , Fibrose Peritoneal/metabolismo , Peritônio/patologia , Valor Preditivo dos Testes , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
15.
Nephrology (Carlton) ; 18(3): 229-34, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23279639

RESUMO

AIM: Obesity represents a significant problem in patients with cardiovascular disease and chronic kidney disease (CKD). The aim of the present study was to investigate the association between body mass index (BMI) and CKD in Thai individuals. METHODS: Participants underwent general health screening. Overweight, weight at risk, obese I and obese II were defined as having a BMI ≥23 kg/m(2), 23-24.9 kg/m(2) , 25-29.9 kg/m(2) and ≥30 kg/m(2), respectively. Waist circumference ≥ 90 cm for men and > 80 cm for women were represented by abdominal obesity. CKD was defined as a glomerular filtration rate (GFR) < 60 mL/min per 1.73 m(2). An estimate of the GFR was obtained by the four-variable Modification of Diet in Renal Disease (MDRD) equation. RESULTS: The study population had 12 348 males and 3009 females. The survey population had a 7.5% prevalence of CKD. There was also a significant graded relationship between the degrees of overweight with the prevalence of CKD. Mean BMI were 25.36 ± 3.29 kg/m(2) for CKD subjects and 24.04 ± 3.13 kg/m(2) for non-CKD subjects (P < 0.001). Prevalence of overweight and abdominal obesity in the participants with CKD were found to be higher than in those without CKD (overweight, 77.6% vs. 61.6%, P < 0.001; abdominal obesity, 35.7% vs. 25.3%, P < 0.001). In a multivariate logistic regression analysis, weight at risk (adjusted odds ratio 1.29; 95% CI 1.07-1.54), obese I (adjusted odds ratio 1.58; 95% CI 1.33-1.87) and obese II (adjusted odds ratio 1.65; 95% CI 1.24-2.19) were associated with CKD. CONCLUSION: Our data showed that overweight and obesity were associated with CKD in Thai members of the army population and their relatives undergoing a general health screening, independently of age, gender, blood pressure, serum lipid, uric acid and glucose levels.


Assuntos
Família , Militares/estatística & dados numéricos , Obesidade Abdominal/epidemiologia , Sobrepeso/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Adulto , Índice de Massa Corporal , Distribuição de Qui-Quadrado , Estudos Transversais , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/fisiopatologia , Modelos Logísticos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Modelos Biológicos , Análise Multivariada , Obesidade Abdominal/diagnóstico , Razão de Chances , Sobrepeso/diagnóstico , Prevalência , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Medição de Risco , Fatores de Risco , Tailândia/epidemiologia , Circunferência da Cintura
16.
J Med Assoc Thai ; 95 Suppl 5: S168-71, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22934464

RESUMO

Cyclosporine can cause acute and chronic nephrotoxicity. Renal biopsy is a reliable tool for the diagnosis of cyclosporine nephrotoxicity. The authors report a 56-year-old Thai female with a history of end-stage renal disease who underwent cadaveric renal transplantation. A transplanted kidney biopsy was performed on day 9 post-transplant to identify the cause of delayed graft function. Light and electron microscopic findings revealed widespread (> 50% involvement) numerous tubules filled with uniformly-sized vacuoles in cytoplasm (isometric vacuolization). Serum cyclosporine trough level was 534 ng/mL. Neither acute rejection nor acute tubular necrosis was seen. Diagnosis of acute cyclosporine nephrotoxicity was made. Isometric vacuolization in more than 50% involvement of the tubules is rare (3%) in biopsy specimens. The tubular isometric vacuolization might not have the strong impact to the long term graft outcome. This is the first case report of isometric tubular vacuolization due to cyclosporine toxicity in renal transplant recipient in Thailand.


Assuntos
Ciclosporina/efeitos adversos , Imunossupressores/efeitos adversos , Transplante de Rim/patologia , Necrose Tubular Aguda/induzido quimicamente , Biópsia , Feminino , Humanos , Túbulos Renais/patologia , Pessoa de Meia-Idade , Tailândia , Vacúolos/patologia
17.
Nephrol Dial Transplant ; 24(5): 1545-9, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-18689790

RESUMO

BACKGROUND: Anti-r-HuEpo associated PRCA developed in patients received subcutaneous injection of r-HuEpo for treatment of renal anemia in chronic kidney disease. This adverse immunological effect of r-HuEpo causes sudden loss of r-HuEpo efficacy, low circulating reticulocyte count and bone marrow biopsy shows an absence of erythroid precursor cells with normal cell population of non-erythroid lineage. There are postulation cause of anti-r-HuEpo associated PRCA including genetic factor, immunogenicity factor, storage and handlings factor and formulation of r-HuEpo product. Previous observation of our report showed an aggregation of HLA-DRB1*09 in four anti-r-HuEpo associated PRCA cases. This allele is rare in Caucasian (<1%) but more common in Thai population (8.4-12.5%). This study was aimed to investigate the possible association between HLA-DRB1*09 or other specific HLA and anti-r-HuEpo associated PRCA. METHODS: Twenty two cases of proven anti-r-HuEpo associated PRCA were recruited and studied retrospectively based on the incidence report of serious adverse drug reaction. The EDTA bloods were drawn for HLA typing using sequence specific primer polymerase chain reaction (SSP-PCR). The HLA data of 1,800 potential cadaveric kidney transplantation recipients in the waiting list as chronic kidney disease control and 1,500 potential bone marrow stem cell donors in national stem cell registry as healthy population control were retrieved from the database of Thai Red Cross for comparison. RESULTS: The distribution of gene frequency of HLA-A, -B, -DR and -DQ alleles in anti-r-HuEpo associated PRCA cases showed high gene frequency of HLA-A*02, HLA-A*11 and HLA-A*24 for HLA-A loci, HLA-B*18, HLA-B*46, HLA-B*60 and HLA-B*62 for HLA-B loci, and HLA-DRB1*09, HLA-DRB1*12 and HLA-DRB1*15 for HLA-DR loci. There was a significant difference of HLA-DRB1*09 gene frequency (P < 0.001) which associated with HLA-DQB1*0309 between anti-r-HuEpo associated PRCA cases, and potential cadaveric kidney transplantation in the waiting list or potential national stem cell registry donor. The odd ratio of HLA-DRB1*09 allele for anti-r-HuEpo associated PRCA was 2.89 (95% CI: 1.88-4.46; p-value: <0.001). CONCLUSIONS: Our data demonstrated the association of HLA-DRB1*09-DQB1*0309 and anti-r-HuEpo associated PRCA cases. This association may be used in identifying the risk of the patients.


Assuntos
Anticorpos Anti-Idiotípicos/imunologia , Eritropoetina/imunologia , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Aplasia Pura de Série Vermelha/genética , Aplasia Pura de Série Vermelha/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Anemia/tratamento farmacológico , Anemia/etiologia , Anticorpos Anti-Idiotípicos/sangue , Estudos de Casos e Controles , Doença Crônica , Eritropoetina/administração & dosagem , Eritropoetina/uso terapêutico , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Antígenos HLA-DQ/imunologia , Cadeias beta de HLA-DQ , Antígenos HLA-DR/imunologia , Cadeias HLA-DRB1 , Humanos , Injeções Subcutâneas , Nefropatias/complicações , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
18.
J Med Assoc Thai ; 88 Suppl 3: S121-30, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16858950

RESUMO

OBJECTIVES: To obtain the prevalence of metabolic syndrome (MS) and its associated socioeconomic factors, and also to evaluate the association between percentage body fat (BF) and body mass index (BMI) in a rural Thai population. MATERIAL AND METHOD: MS defined by the National Cholesterol Education Program Adult Treatment Panel III criteria. The prevalence of the MS was then determined using the NCEP III criteria with and without the modified waist circumference criteria. BMI indicating normal weight, overweight and obesity as re-defined for the Asian by International Association for the Study of Obesity (IASO), WHO. Four-hundred and four rural Thai men and women aged 35 years and older were evaluated. Data on anthropometry, blood pressure, socioeconomic status, lifestyle-related information, blood studies, and bioelectrical impedance (BIA) values had been collected. RESULTS: The prevalence of the MS in the rural Thai people was 18%, but increased to 23% with the modified Asian criteria. High BMI, female gender, and older age were associated with increased odds of the MS. Household income, dietary composition, smoking and drinking status were not associated with increased odds of the MS. There was significant association between percent BF and BMI in men and women in rural Thai population. CONCLUSION: The MS was present in about 18% of the rural Thai population and was significantly influenced by body mass index, gender and age. Metabolic syndrome becomes an important problem in rural Thai populations who even live basic lifestyle in the non-urbanized and non-industrialized areas. Identification and clinical management of this high-risk group is an important strategy for coronary heart disease prevention.


Assuntos
Composição Corporal , Índice de Massa Corporal , Síndrome Metabólica/epidemiologia , Saúde da População Rural , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Fatores Socioeconômicos , Tailândia
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