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3.
Am J Physiol Renal Physiol ; 318(6): F1418-F1429, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32308019

RESUMO

The use of high dialysate bicarbonate for hemodialysis in end-stage renal disease is associated with increased mortality, but potential physiological mediators are poorly understood. Alkalinization due to high dialysate bicarbonate may stimulate organic acid generation, which could lead to poor outcomes. Using measurements of ß-hydroxybutyrate (BHB) and lactate, we quantified organic anion (OA) balance in two single-arm studies comparing high and low bicarbonate prescriptions. In study 1 (n = 10), patients became alkalemic using 37 meq/L dialysate bicarbonate; in contrast, with the use of 27 meq/L dialysate, net bicarbonate loss occurred and blood bicarbonate decreased. Total OA losses were not higher with 37 meq/L dialysate bicarbonate (50.9 vs. 49.1 meq using 27 meq/L, P = 0.66); serum BHB increased in both treatments similarly (P = 0.27); and blood lactate was only slightly higher with the use of 37 meq/L dialysate (P = 0.048), differing by 0.2 meq/L at the end of hemodialysis. In study 2 (n = 7), patients achieved steady state on two bicarbonate prescriptions: they were significantly more acidemic when dialyzed against a 30 meq/L bicarbonate dialysate compared with 35 meq/L and, as in study 1, became alkalemic when dialyzed against the higher bicarbonate dialysate. OA losses were similar to those in study 1 and again did not differ between treatments (38.9 vs. 43.5 meq, P = 0.42). Finally, free fatty acid levels increased throughout hemodialysis and correlated with the change in serum BHB (r = 0.81, P < 0.001), implicating upregulation of lipolysis as the mechanism for increased ketone production. In conclusion, lowering dialysate bicarbonate does not meaningfully reduce organic acid generation during hemodialysis or modify organic anion losses into dialysate.

4.
Nephrol Dial Transplant ; 35(5): 846-853, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30879076

RESUMO

BACKGROUND: Residual kidney function (RKF) is thought to exert beneficial effects through clearance of uremic toxins. However, the level of native kidney function where clearance becomes negligible is not known. METHODS: We aimed to assess whether levels of nonurea solutes differed among patients with 'clinically negligible' RKF compared with those with no RKF. The hemodialysis study excluded patients with urinary urea clearance >1.5 mL/min, below which RKF was considered to be 'clinically negligible'. We measured eight nonurea solutes from 1280 patients participating in this study and calculated the relative difference in solute levels among patients with and without RKF based on measured urinary urea clearance. RESULTS: The mean age of the participants was 57 years and 57% were female. At baseline, 34% of the included participants had clinically negligible RKF (mean 0.7 ± 0.4 mL/min) and 66% had no RKF. Seven of the eight nonurea solute levels measured were significantly lower in patients with RKF than in those without RKF, ranging from -24% [95% confidence interval (CI) -31 to -16] for hippurate, -7% (-14 to -1) for trimethylamine-N-oxide and -4% (-6 to -1) for asymmetric dimethylarginine. The effect of RKF on plasma levels was comparable or more pronounced than that achieved with a 31% higher dialysis dose (spKt/Vurea 1.7 versus 1.3). Preserved RKF at 1-year follow-up was associated with a lower risk of cardiac death and first cardiovascular event. CONCLUSIONS: Even at very low levels, RKF is not 'negligible', as it continues to provide nonurea solute clearance. Management of patients with RKF should consider these differences.

5.
Am J Kidney Dis ; 75(2): 225-234, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31699517

RESUMO

RATIONALE & OBJECTIVE: Metabolic acidosis associated with chronic kidney disease (CKD) may contribute to muscle dysfunction and bone disease. We aimed to test whether treatment with sodium bicarbonate improves muscle and bone outcomes. STUDY DESIGN: Multicenter, randomized, placebo-controlled, clinical trial. SETTING & PARTICIPANTS: 149 patients with CKD stages 3 and 4 between July 2011 and April 2016 at 3 centers in Cleveland, OH, and the Bronx, NY. INTERVENTION: Sodium bicarbonate (0.4 mEq per kg of ideal body weight per day) (n=74) or identical-appearing placebo (n=75). OUTCOMES: Dual primary outcomes were muscle function assessed using sit-to-stand test and bone mineral density. Muscle biopsies were performed at baseline and 2 months. Participants were seen at baseline and 2, 6, 12, and 24 months. RESULTS: Mean baseline serum bicarbonate level was 24.0±2.2 (SD) mEq/L and mean baseline estimated glomerular filtration rate was 36.3±11.2mL/min/1.73m2. Baseline characteristics did not differ between groups. Mean serum bicarbonate levels in the intervention arm during follow-up were 26.4±2.2, 25.5±2.3, 25.6±2.6, and 24.4±2.8 mEq/L (at 2, 6, 12, and 24 months). These were significantly higher than in the placebo group (P<0.001). Compared to the placebo group, participants randomly assigned to sodium bicarbonate treatment had no significant differences in sit-to-stand time (5 repetitions: P=0.1; and 10 repetitions P=0.07) or bone mineral density (P=0.3). Sodium bicarbonate treatment caused a decrease in serum potassium levels that was of borderline statistical significance (P=0.05). There were no significant differences in estimated glomerular filtration rates, blood pressure, weight, serious adverse events, or levels of muscle gene expression between the randomly assigned groups. LIMITATIONS: Initial mean serum bicarbonate level was in the normal range. CONCLUSIONS: Sodium bicarbonate therapy in patients with CKD stages 3 and 4 significantly increases serum bicarbonate and decreases potassium levels. No differences were found in muscle function or bone mineral density between the randomly assigned groups. Larger trials are required to evaluate effects on kidney function. FUNDING: National Institutes of Health grant. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT01452412.


Assuntos
Taxa de Filtração Glomerular/fisiologia , Insuficiência Renal Crônica/tratamento farmacológico , Bicarbonato de Sódio/administração & dosagem , Bicarbonatos/sangue , Biomarcadores/sangue , Progressão da Doença , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Potássio/sangue , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
6.
J Am Soc Nephrol ; 31(1): 161-174, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31848294

RESUMO

BACKGROUND: Oral sodium bicarbonate (NaHCO3) may preserve kidney function in CKD, even if initiated when serum bicarbonate concentration is normal. Adequately powered trials testing this hypothesis have not been conducted, partly because the best dose for testing is unknown. METHODS: This multicenter pilot trial assessed the safety, tolerability, adherence, and pharmacodynamics of two doses of NaHCO3 over 28 weeks in adults with eGFR 20-44 or 45-59 ml/min per 1.73 m2 with urinary albumin/creatinine (ACR) ≥50 mg/g and serum bicarbonate 20-28 meq/L. We randomly assigned 194 participants from ten clinical sites to receive higher-dose (HD-NaHCO3; 0.8 meq/kg of lean body wt per day; n=90) or lower-dose (LD-NaHCO3; 0.5 meq/kg of lean body wt per day; n=52) NaHCO3 or matching placebo (n=52). The dose was adjusted depending on side effects. The prescribed dose at week 28 was the primary outcome; a dose was considered acceptable for a full-scale trial if ≥67% of participants were on full-dose and ≥80% were on ≥25% of the per-protocol dose. RESULTS: Mean±SD baseline eGFR was 36±9 ml/min per 1.73 m2, serum bicarbonate was 24±2 meq/L, and median (IQR) ACR was 181 (25-745) mg/g. Both doses were well tolerated without significant changes in BP, weight, or serum potassium. The proportions of adverse events and hospitalizations were similar across the groups. Consequently, 87% in HD-NaHCO3, 96% in LD-NaHCO3, and 87% in placebo were on full dose at week 28; and 91% in HD-NaHCO3, 98% in LD-NaHCO3, and 92% in placebo were on ≥25% of the per-protocol dose. Mean urinary ammonium excretion was 25% lower and serum bicarbonate concentration was 1.3 meq/L higher in HD-NaHCO3 compared with LD-NaHCO3 at week 28. However, mean ACR increased by 12% in the lower-dose group and 30% in the higher-dose group. CONCLUSIONS: Both NaHCO3 doses were well tolerated over 28 weeks with no significant difference in adverse events or hospitalization compared with placebo. The higher dose lowered urinary ammonium excretion and increased serum bicarbonate more than the lower dose but was associated with a greater increase in ACR. The higher 0.8 meq/kg of lean body wt per day dose of NaHCO3 may be a reasonable choice for future trials.

9.
Br J Clin Pharmacol ; 85(4): 849-853, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30677159

RESUMO

This study presents outcome and pharmacokinetics of arsenic trioxide (ATO) metabolites in patients on continuous venovenous haemodialysis (CVVHD). Of 3 acute promyelocytic leukaemia patients receiving CVVHD in management of acute kidney injury, only 1 patient was included. The patient presented disseminated intravascular coagulation and acute kidney injury before induction therapy was conducted. CVVHD was performed and ATO was initiated. Species of ATO metabolites in plasma and effluent were analysed using high performance liquid chromatography-hydride generation-atomic fluorescence spectrometry. Plasma concentrations of AsIII , monomethylarsonic acid and dimethylarsinic acid with CVVHD were lower than those without CVVHD. Area under the concentration-time curve from 0 to the last sample with quantifiable concentration of AsIII without CVVHD was significantly higher than that with CVVHD (292.10 ng h/mL vs 195.86 ng h/mL, P = .037), which were not observed for monomethylarsonic acid and dimethylarsinic acid. Dialysate saturation of arsenic species was remarkable, especially for AsIII . Complete remission was achieved and renal function recovered. In this study, ATO can be used safely and effectively to treat acute promyelocytic leukaemia patients undergoing CVVHD without dose adjustment.


Assuntos
Lesão Renal Aguda/terapia , Antineoplásicos/farmacocinética , Trióxido de Arsênio/farmacocinética , Terapia de Substituição Renal Contínua , Leucemia Promielocítica Aguda/tratamento farmacológico , Lesão Renal Aguda/sangue , Lesão Renal Aguda/etiologia , Idoso , Antineoplásicos/administração & dosagem , Área Sob a Curva , Trióxido de Arsênio/administração & dosagem , Relação Dose-Resposta a Droga , Humanos , Leucemia Promielocítica Aguda/sangue , Masculino , Estudos Prospectivos , Indução de Remissão/métodos , Estudos de Caso Único como Assunto , Resultado do Tratamento
10.
Artigo em Inglês | MEDLINE | ID: mdl-32163578

RESUMO

BACKGROUND: Low serum bicarbonate level is associated with increased mortality, but its role as a predictor of cardiovascular disease (CVD) is unclear. This study evaluates the association between serum bicarbonate concentration and CVD and whether the effect of intensive blood pressure (BP) lowering on CVD outcomes is modified by serum bicarbonate level. METHODS: The Systolic Blood Pressure Intervention Trial (SPRINT) randomized participants to a systolic BP target <120 mmHg (intensive treatment) or <140 mmHg (standard treatment). The primary CVD outcome was a composite of nonfatal myocardial infarction (MI), acute coronary syndrome not resulting in MI, stroke, acute decompensated heart failure and CVD death. Cox proportional hazards models adjusted for demographic, clinical and laboratory characteristics were used to evaluate the association of interest in 9334 SPRINT participants (ClinicalTrials.gov: NCT01206062). RESULTS: Over a median follow-up of 3.33 years (interquartile range 2.87-3.87 years), 618 (6.6%) participants experienced a primary CVD outcome. Participants with serum bicarbonate <22 mEq/L had a significantly higher risk of the primary CVD outcome (hazard ratio 1.54; 95% confidence interval 1.11-2.14, P = 0.01), compared with participants with bicarbonate 22-26 mEq/L. The magnitude of the CVD risk reduction with intensive BP lowering was similar across bicarbonate strata (P-value for interaction = 0.97). CONCLUSIONS: In hypertensive individuals, serum bicarbonate level <22 mEq/L was associated with an increased CVD risk. The effect of intensive BP lowering on CVD outcomes was not modified by the serum bicarbonate level.

12.
Clin J Am Soc Nephrol ; 13(4): 596-603, 2018 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-29567858

RESUMO

BACKGROUND AND OBJECTIVES: Cognitive function worsens as kidney function declines, but mechanisms contributing to this association are not completely understood. Metabolic acidosis, a common complication of CKD, leads to neural networks overexcitation and is involved in cerebral autoregulation. We aimed to evaluate the association between serum bicarbonate concentration as a measure of metabolic acidosis, and cognitive function in hypertensive adults with and without CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Five cognitive summary scores were measured (global cognitive function, executive function, memory, attention/concentration, and language) in 2853 participants in the Systolic BP Intervention Trial (SPRINT). Multivariable linear regression models adjusted for demographics, comorbidities, systolic BP, medications, eGFR and albuminuria evaluated the cross-sectional association between bicarbonate and cognition at SPRINT baseline. In a subset (n=681) who underwent brain magnetic resonance imaging, the models were adjusted for white matter hyperintensity volume, vascular reactivity, and cerebral blood flow. RESULTS: The mean age (SD) was 68 (8.5) years. Global cognitive and executive functions were positively associated with serum bicarbonate (estimate [SEM]: 0.014 [0.006]; P=0.01, and 0.018 [0.006]; P=0.003, respectively). Each 1 mEq/L lower bicarbonate level had a similar association with global cognitive and executive function as being 4.3 and 5.4 months older, respectively. The association with global cognition persisted after magnetic resonance imaging findings adjustment (estimate [SEM]: 0.03 [0.01]; P=0.01). There was no association between serum bicarbonate level and memory, attention/concentration, and language. CONCLUSIONS: In a large cohort of hypertensive adults, higher serum bicarbonate levels were independently associated with better global cognitive and executive performance. (ClinicalTrials.gov: NCT01206062).


Assuntos
Bicarbonatos/sangue , Cognição , Hipertensão/fisiopatologia , Insuficiência Renal Crônica/fisiopatologia , Acidose/sangue , Acidose/etiologia , Idoso , Encéfalo/diagnóstico por imagem , Estudos Transversais , Função Executiva , Feminino , Taxa de Filtração Glomerular , Humanos , Hipertensão/complicações , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Testes Neuropsicológicos , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal Crônica/complicações
13.
J Am Soc Nephrol ; 29(2): 355-356, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29371422
14.
Clin J Am Soc Nephrol ; 13(2): 223-230, 2018 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-29146699

RESUMO

BACKGROUND AND OBJECTIVES: Urinary ammonium excretion increases in response to nonvolatile acids to maintain normal systemic bicarbonate and pH. However, enhanced ammonia production promotes tubulointerstitial fibrosis in animal models. Therefore, a subset of individuals with CKD and normal bicarbonate may have acid-mediated kidney fibrosis that might be better linked with ammonium excretion than bicarbonate. We hypothesized that urine TGF-ß1, as an indicator of kidney fibrosis, would be more tightly linked with urine ammonium excretion than serum bicarbonate and other acid-base indicators. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We measured serum bicarbonate and urinary ammonium, titratable acids, pH, and TGF-ß1/creatinine in 144 persons with CKD. Multivariable-adjusted linear regression models determined the cross-sectional association between TGF-ß1/creatinine and serum bicarbonate, urine ammonium excretion, urine titratable acids excretion, and urine pH. RESULTS: Mean eGFR was 42 ml/min per 1.73 m2, mean age was 65 years old, 78% were men, and 62% had diabetes. Mean urinary TGF-ß1/creatinine was 102 (49) ng/g, mean ammonium excretion was 1.27 (0.72) mEq/h, mean titratable acids excretion was 1.14 (0.65) mEq/h, mean urine pH was 5.6 (0.5), and mean serum bicarbonate was 23 (3) mEq/L. After adjusting for eGFR, proteinuria, and other potential confounders, each SD increase of urine ammonium and urine pH was associated with a statistically significant 1.22-fold (95% confidence interval, 1.11 to 1.35) or 1.11-fold (95% confidence interval, 1.02 to 1.21) higher geometric mean urine TGF-ß1/creatinine, respectively. Each SD increase of serum bicarbonate and urine titratable acids was associated with a nonsignificant 1.06-fold (95% confidence interval, 0.97 to 1.16) or 1.03-fold (95% confidence interval, 0.92 to 1.14) higher geometric mean urine TGF-ß1/creatinine, respectively. CONCLUSIONS: Urinary ammonium excretion but not serum bicarbonate is associated with higher urine TGF-ß1/creatinine.


Assuntos
Compostos de Amônio/urina , Insuficiência Renal Crônica/urina , Fator de Crescimento Transformador beta1/urina , Idoso , Idoso de 80 Anos ou mais , Bicarbonatos/sangue , Biomarcadores/sangue , Biomarcadores/urina , Creatinina/urina , Estudos Transversais , Feminino , Fibrose , Taxa de Filtração Glomerular , Humanos , Concentração de Íons de Hidrogênio , Rim/patologia , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Eliminação Renal , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia
16.
Kidney Int ; 92(6): 1484-1492, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28739139

RESUMO

Cardiovascular disease, the leading cause of mortality in hemodialysis patients, is not fully explained by traditional risk factors. To help define non-traditional risk factors, we determined the association of predialysis total p-cresol sulfate, indoxyl sulfate, phenylacetylglutamine, and hippurate with cardiac death, sudden cardiac death, and first cardiovascular event in the 1,273 participants of the HEMO Study. The results were adjusted for potential demographic, clinical, and laboratory confounders. The mean age of the patients was 58 years, 63% were Black and 42% were male. Overall, there was no association between the solutes and outcomes. However, in sub-group analyses, among patients with lower serum albumin (under 3.6 g/dl), a twofold higher p-cresol sulfate was significantly associated with a 12% higher risk of cardiac death (hazard ratio 1.12; 95% confidence interval, 0.98-1.27) and 22% higher risk of sudden cardiac death (1.22, 1.06-1.41). Similar trends were also noted with indoxyl sulfate. Trial interventions did not modify the association between these solutes and outcomes. Routine clinical and lab data explained less than 22% of the variability in solute levels. Thus, in prevalent hemodialysis patients participating in a large U.S. hemodialysis trial, uremic solutes p-cresol sulfate, indoxyl sulfate, hippurate, and phenylacetylglutamine were not associated with cardiovascular outcomes. However, there were trends of toxicity among patients with lower serum albumin.


Assuntos
Doenças Cardiovasculares/sangue , Cresóis/sangue , Indicã/sangue , Falência Renal Crônica/terapia , Diálise Renal/efeitos adversos , Ésteres do Ácido Sulfúrico/sangue , Adulto , Idoso , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Feminino , Glutamina/análogos & derivados , Glutamina/sangue , Hipuratos/sangue , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Falência Renal Crônica/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Diálise Renal/estatística & dados numéricos , Fatores de Risco , Albumina Sérica/análise , Uremia/sangue , Uremia/complicações
17.
Medicine (Baltimore) ; 96(6): e5799, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28178126

RESUMO

The uremic syndrome is attributed to progressive retention of compounds that, under normal conditions, are excreted by the healthy kidneys. p-cresol sulfate (PCS), a prototype protein-bound uremic retention solute, has been shown to exert toxic effects in vitro. Recent studies have identified relations between increased levels of PCS and indoxyl sulfate (IS) and adverse clinical outcomes in hemodialysis patients. We explored the relationship between free and total PCS and IS with infection-related hospitalizations (IH) and septicemia in 2 cohorts, Choices for Healthy Outcomes in Caring for end-stage renal disease (ESRD) Study (CHOICE) and Hemodialysis Study (HEMO).We measured free and total levels of PCS and IS in stored specimens in CHOICE, a cohort of 464 incident hemodialysis patients enrolled in 1995 to 1998 and followed for an average of 3.4 years and in a prevalent dialysis cohort of 495 patients enrolled in HEMO from 1995 to 2000 and followed for an average of 4.4 years. We measured free PCS and IS using mass spectroscopy. The 2 cohorts were linked to United States Renal Data System (USRDS) Medicare billing records to ascertain IH over follow-up. We examined the association of free and total levels of PCS and IS with IH and septicemia using multilevel Poisson regression models adjusted for demographics, comorbidities, clinical factors, and laboratory tests including residual kidney function. We stratified patients a priori based on gastrointestinal (GI) disease as PCS and IS are produced in colon.In CHOICE, highest tertile of free PCS in multivariable model was associated with 50% higher risk of IH [95% CI = 1.01-2.23] compared with lowest tertile in patients with no-GI disease. A significant trend was noted between greater levels of free PCS and septicemia in no-GI disease group in both cohorts, while no association was noted in GI disease group. Total PCS concentrations were not associated with either IH or septicemia in either cohort. No significant risk of IH or septicemia was noted with higher levels of free or total IS in either GI or no-GI disease group.These results suggest an association between higher concentrations of free PCS and infection-related and sepsis-related hospitalizations in hemodialysis patients. Better methods of dialysis should be developed to evaluate the utility of removing PCS and its effect on the outcome and also therapies to decrease gastrointestinal tract production of uremic solutes.


Assuntos
Cresóis/sangue , Gastroenteropatias/complicações , Indicã/sangue , Falência Renal Crônica/sangue , Sepse/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Admissão do Paciente/estatística & dados numéricos , Sepse/etiologia , Adulto Jovem
18.
Am J Kidney Dis ; 70(1): 48-58, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28089476

RESUMO

BACKGROUND: Asymmetric (ADMA) and symmetric dimethylarginine (SDMA) are putative uremic toxins that may exert toxicity by a number of mechanisms, including impaired nitric oxide synthesis and generation of reactive oxygen species. The study goal was to determine the association between these metabolites and cardiovascular outcomes in hemodialysis patients. STUDY DESIGN: Post hoc analysis of the Hemodialysis (HEMO) Study. SETTING & PARTICIPANTS: 1,276 prevalent hemodialysis patients with available samples 3 to 6 months after randomization. PREDICTOR: ADMA and SDMA measured in stored specimens. OUTCOMES: Cardiac death, sudden cardiac death, first cardiovascular event, and any-cause death. Association with predictors analyzed using Cox regression adjusted for potential confounders (including demographics, clinical characteristics, comorbid conditions, albumin level, and residual kidney function). RESULTS: Mean age of patients was 57±14 (SD) years, 63% were black, and 57% were women. Mean ADMA (0.9±0.2µmol/L) and SDMA levels (4.3±1.4µmol/L) were moderately correlated (r=0.418). Higher dialysis dose or longer session length were not associated with lower predialysis ADMA or SDMA concentrations. In fully adjusted models, each doubling of ADMA level was associated with higher risk (HR per 2-fold higher concentration; 95% CI) of cardiac death (1.83; 1.29-2.58), sudden cardiac death (1.79; 1.19-2.69), first cardiovascular event (1.50; 1.20-1.87), and any-cause death (1.44; 1.13-1.83). Compared to the lowest ADMA quintile (<0.745 µmol/L), the highest ADMA quintile (≥1.07µmol/L) was associated with higher risk (HR; 95% CI) of cardiac death (2.10; 1.44-3.05), sudden cardiac death (2.06; 1.46-2.90), first cardiovascular event (1.75; 1.35-2.27), and any-cause death (1.56; 1.21-2.00). SDMA level was associated with higher risk for cardiac death (HR, 1.40; 95% CI, 1.03-1.92), but this was no longer statistically significant after adjusting for ADMA level (HR, 1.20; 95% CI, 0.86-1.68). LIMITATIONS: Single time-point measurement of ADMA and SDMA. CONCLUSIONS: ADMA and, to a lesser extent, SDMA levels are associated with cardiovascular outcomes in hemodialysis patients.


Assuntos
Arginina/análogos & derivados , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Diálise Renal , Arginina/sangue , Doenças Cardiovasculares/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade , Estudos Prospectivos
19.
J Am Soc Nephrol ; 28(1): 321-331, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27436853

RESUMO

Cardiovascular disease causes over 50% of the deaths in dialysis patients, and the risk of death is higher in white than in black patients. The underlying mechanisms for these findings are unknown. We determined the association of the proatherogenic metabolite trimethylamine N-oxide (TMAO) with cardiovascular outcomes in hemodialysis patients and assessed whether this association differs by race. We measured TMAO in stored serum samples obtained 3-6 months after randomization from a total of 1232 white and black patients of the Hemodialysis Study, and analyzed the association of TMAO with cardiovascular outcomes using Cox models adjusted for potential confounders (demographics, clinical characteristics, comorbidities, albumin, and residual kidney function). Mean age of the patients was 58 years; 35% of patients were white. TMAO concentration did not differ between whites and blacks. In whites, 2-fold higher TMAO associated with higher risk (hazard ratio [95% confidence interval]) of cardiac death (1.45 [1.24 to 1.69]), sudden cardiac death [1.70 (1.34 to 2.15)], first cardiovascular event (1.15 [1.01 to 1.32]), and any-cause death (1.22 [1.09 to 1.36]). In blacks, the association was nonlinear and significant only for cardiac death among patients with TMAO concentrations below the median (1.58 [1.03 to 2.44]). Compared with blacks in the same quintile, whites in the highest quintile for TMAO (≥135 µM) had a 4-fold higher risk of cardiac or sudden cardiac death and a 2-fold higher risk of any-cause death. We conclude that TMAO concentration associates with cardiovascular events in hemodialysis patients but the effects differ by race.


Assuntos
Doenças Cardiovasculares/epidemiologia , Metilaminas/sangue , Diálise Renal , Grupo com Ancestrais do Continente Africano , Doenças Cardiovasculares/etiologia , Grupo com Ancestrais do Continente Europeu , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
20.
BMC Nephrol ; 17(1): 114, 2016 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-27495287

RESUMO

BACKGROUND: The regulation of fibroblast growth factor-23 (FGF23) secretion in patients with chronic kidney disease (CKD) is incompletely understood. An in vitro study showed that metabolic acidosis increased FGF23 in mouse bone. The objective of this study is to evaluate the effect of oral sodium bicarbonate on circulating FGF23 levels in patients with CKD. METHODS: This was a single-blind pilot study. Twenty adults with estimated glomerular filtration rate between 15-45 mL/min/1.73 m(2) and serum bicarbonate between 20-24 mEq/L were treated with placebo for 2 weeks, followed by increasing doses of oral sodium bicarbonate (0.3, 0.6 and 1.0 mEq/kg/day) in 2 week intervals for a total of 6 weeks. C-terminal FGF23 levels were measured at the initial visit, after 2 weeks of placebo and after 6 weeks of bicarbonate therapy. Wilcoxon matched-pairs signed-rank test was used to compare FGF23 before and after sodium bicarbonate. RESULTS: After 6 weeks of oral sodium bicarbonate, the median FGF23 increased significantly from 150.9 RU/mL (IQR 107.7-267.43) to 191.4 RU/mL (IQR 132.6-316.9) (p = 0.048) and this persisted after excluding participants who received activated vitamin D. CONCLUSIONS: FGF23 increased after short-term oral sodium bicarbonate therapy in patients with CKD and mild metabolic acidosis. It is unclear whether this was due to the alkalinizing effect of sodium bicarbonate or other factors. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov ( NCT00888290 ) on April 23, 2009.


Assuntos
Fatores de Crescimento de Fibroblastos/sangue , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/tratamento farmacológico , Bicarbonato de Sódio/administração & dosagem , Administração Oral , Idoso , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Insuficiência Renal Crônica/fisiopatologia , Método Simples-Cego
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