RESUMO
BACKGROUND/AIMS: Mortality in end-stage renal disease patients with dialysis remains high. A high percentage of dialysis patients display signs of chronic microinflammation. To clarify whether microinflammation is involved in the high incidence of poor prognosis in dialysis patients, we investigated the association of inflammatory markers with mortality in a prospective observational cohort study. METHODS: 120 patients undergoing hemodialysis were enrolled. Baseline cross-sectional analysis of the relationship between inflammatory markers [interleukin-6 (IL-6), tumor necrosis factor-alpha and high-sensitivity C-reactive protein] and other factors, along with a survival analysis for death, were performed. All subjects were divided into 2 groups according to the median value of IL-6. RESULTS: The mortality rate was significantly higher in the high (20.0%) compared with the low IL-6 group (3.3%, p = 0.0046). Receiver-operating characteristic curves indicated high mortality to be closely associated with a high IL-6 level rather than tumor necrosis factor-alpha. In stepwise multiple regression analyses, age, phosphorus and high-sensitivity C-reactive protein were independent predictors of IL-6 (R(2) = 0.466, p < 0.0001). CONCLUSIONS: These data clearly show that plasma IL-6 is a powerful predictor of all-cause mortality in dialysis patients.
Assuntos
Interleucina-6/sangue , Falência Renal Crônica/sangue , Falência Renal Crônica/mortalidade , Diálise Renal/mortalidade , Feminino , Seguimentos , Humanos , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Curva ROC , Análise de Regressão , Fatores de Risco , Fator de Necrose Tumoral alfa/sangueRESUMO
OBJECTIVE: Tumor necrosis factor (TNF)-alpha-induced endothelial injury, which is associated with atherosclerosis, is mediated by intracellular reactive oxygen species. Iron is essential for the amplification of oxidative stress. We tested whether TNF-alpha accelerated iron accumulation in vascular endothelium, favoring synthesis of hydroxyl radical. METHODS AND RESULTS: Diverse iron transporters, including iron import proteins (transferrin receptor [TfR] and divalent metal transporter 1 [DMT1]) and an iron export protein (ferroportin 1 [FP1]) coexist in human umbilical endothelial cells (HUVECs). TNF-alpha caused upregulation of TfR and DMT1 and downregulation of FP1, which were demonstrated in mRNA as well as protein levels. These changes in iron transporters were accompanied by accumulation of iron that was both transferrin-dependent and transferrin-independent. Modifications of these mRNAs were regulated post-transcriptionally, and were coordinated with activation of binding activity of iron regulatory protein 1 to the iron responsive element on transporter mRNAs. Using a salicylate trap method, we observed that only simultaneous exposure of endothelial cells to iron and TNF-alpha accelerated hydroxyl radical production. CONCLUSIONS: TNF-alpha could cause intracellular iron sequestration, which may participate importantly in the pathophysiology of atherosclerosis and cardiovascular disease.
Assuntos
Aterosclerose/metabolismo , Endotélio Vascular/metabolismo , Ferro/metabolismo , Estresse Oxidativo/fisiologia , Fator de Necrose Tumoral alfa/metabolismo , Aconitato Hidratase/antagonistas & inibidores , Aconitato Hidratase/metabolismo , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Células Cultivadas , Regulação para Baixo , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Humanos , Radical Hidroxila/metabolismo , Imuno-Histoquímica , Radioisótopos de Ferro , Proteína 1 Reguladora do Ferro/metabolismo , Proteínas Reguladoras de Ferro/metabolismo , Estresse Oxidativo/efeitos dos fármacos , RNA Mensageiro/metabolismo , Receptores da Transferrina/genética , Receptores da Transferrina/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Veias Umbilicais/citologia , Regulação para CimaRESUMO
We tested the effect of three different dialysate calcium concentrations on calcium-phosphorus metabolism during the use of sevelamer hydrochloride. After a calcium-containing phosphate binder was switched to sevelamer, the serum calcium, phosphorus, and intact parathyroid hormone levels and the markers of bone turnover were measured in the patients whose dialysate calcium concentrations were 2.5, 2.75, and 3.0 mEq/L. As a result, in the 2.75-mEq/L group, the serum calcium concentrations decreased and the intact parathyroid hormone level increased significantly. In the 2.5-mEq/L group, transient hypocalcemia occurred and the levels of both bone-alkaline phosphatase and osteocalcin increased. In the 3.0-mEq/L group, the serum calcium concentrations did not change significantly and only bone-alkaline phosphatase increased. If a calcium-containing phosphate binder is completely switched to sevelamer, dialysis using a dialysate calcium concentration below 3.0 mEq/L may result in hypocalcemia and acceleration of bone turnover.