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BACKGROUND: Malnutrition is a frequently observed disorder in patients with chronic kidney disease (CKD) receiving hemodialysis (HD). While variously defined, malnutrition is a frequently observed condition among patients on HD. Prevalence estimates of malnutrition among Israeli HD patients have not been reported. OBJECTIVES: To survey nutrition intake in Israeli HD patients; estimate malnutrition risk prevalence; identify risk factors, and characterize malnutrition risk in HD patients. METHODS: A representative sample of 378 Israeli HD patients treated in hospital HD centers throughout the country were surveyed. Using the 24-h recall method, dietary intake was estimated and the chronologically corresponding biochemistry, anthropometric, and hemodynamic measures were recorded. Four categories of malnutrition risk were defined: "minimal": body mass index (BMI) > 23 kg/m2 and serum albumin > 3.8 g/dL; "mild": BMI < 23 kg/m2 and albumin > 3.8 g/dL; "moderate": BMI > 23 kg/m2 and albumin < 3.8 g/dL; "severe": BMI < 23 k/m2 and serum albumin < 3.8 g/dL. RESULTS: Elevated malnutrition risk was identified in 175 (46.3%) study participants, who were more likely to require feeding assistance, have major comorbidities, reduced hemoglobin, and elevated C-reactive protein. Oral nutrition supplementation was prescribed to only 14.3% of patients with elevated malnutrition risk. Intradialytic parenteral nutrition was recorded for 6 patients, all of whom had moderate or severe malnutrition risk. Less than one-third of patients met the guidelines for dietary intake of energy or protein, and this did not differ across malnutrition risk groups. DISCUSSION: Elevated malnutrition risk is a frequent finding in HD patients treated in hospital settings in Israel. Dietary intake does not meet guidelines but does not differ across malnutrition risk categories. Nutrition supplements are underused in HD patients with high malnutrition risk. There is a need to expand the survey to community HD centers.
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Encuestas Epidemiológicas , Desnutrición/etiología , Estado Nutricional , Diálisis Renal/efectos adversos , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/terapia , Anciano , Estudios Transversales , Femenino , Humanos , Israel , Masculino , Persona de Mediana EdadRESUMEN
The Interleukin 1 (IL-1) family plays a central role in the generation and regulation of inflammatory responses, in both innate and adaptive immunity. Although the IL-1 molecules are traditionally considered to be classical proinflammatory cytokines, their functions are not restricted to inflammation, and they have also been shown to play a key role in a wide range of additional physiological and pathological functions, including learning modulation, sleep, pregnancy, depression, appetite, hematopoiesis, metabolism, and many others. Since their effect as cytokines and regulators of inflammation is so pleiotropic, any shift of the biological balance between agonistic and antagonistic signals has the potential to cause disease. Here, we consider the genetic influence of interleukin-1 gene polymorphism in the context of susceptibility to human diseases. We review known single nucleotide polymorphisms (SNP) of IL-1 genes linked to human diseases, and suggest how exploring biological effects of IL-1 gene cluster polymorphism may lead to new directions in understanding and diagnostic of disease and effective treatment.
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Enfermedades Cardiovasculares/inmunología , Artropatías por Depósito de Cristales/inmunología , Diabetes Mellitus Tipo 2/inmunología , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Interleucina-1/genética , Lupus Eritematoso Sistémico/inmunología , Enfermedades Neurodegenerativas/inmunología , Espondilitis Anquilosante/inmunología , Inmunidad Adaptativa , Artritis Juvenil , Diabetes Mellitus Tipo 2/terapia , Predisposición Genética a la Enfermedad , Humanos , Inmunidad Innata , Polimorfismo GenéticoRESUMEN
Atherosclerosis and cardiovascular complications are prevalent among patients undergoing chronic hemodialysis (HD). In this population, peripheral polymorphonuclear leukocytes (PMNLs) are primed, releasing proinflammatory mediators such as elastase. Elastase is normally inhibited by a specific inhibitor, avoiding undesirable degradation of cellular and extracellular components. This study tested the hypothesis that in states of noninfectious inflammation, elastase is released by PMNLs and acts in an uncontrolled manner to inflict vascular damage. Blood was collected from patients undergoing HD and healthy controls (HC). PMNL intracellular and surface expressions of elastase were determined by quantitative real-time PCR, Western blotting, and flow cytometry. The elastase activity was evaluated using a fluorescent substrate. The levels of serum α1-antitrypsin (α1-AT), the natural elastase inhibitor, were determined by Western blot. Free active elastase was elevated in HD sera, whereas the levels of α1-AT were decreased compared with HC. The levels of the intracellular elastase enzyme and its activity were lower in HD PMNLs despite similar expression levels of elastase mRNA. Elastase binding to PMNL cell surface was higher in HD compared with HC. The increased circulating levels of free active elastase released from primed HD PMNLs together with the higher cell surface-bound enzymes and the lower levels of α1-AT result in the higher elastase activity in HD sera. This exacerbated elastase activity could lead to the endothelial dysfunction, as hypothesized. In addition, it suggests that free circulating elastase can serve as a new biomarker and therapeutic target to reduce inflammation and vascular complications in patients on hemodialysis.
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Mediadores de Inflamación/sangre , Inflamación/etiología , Fallo Renal Crónico/terapia , Elastasa de Leucocito/sangre , Activación Neutrófila , Neutrófilos/enzimología , Diálisis Renal/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Estudios de Casos y Controles , Enfermedad Crónica , Femenino , Humanos , Inflamación/sangre , Inflamación/diagnóstico , Inflamación/enzimología , Fallo Renal Crónico/sangre , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/enzimología , Elastasa de Leucocito/genética , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Regulación hacia Arriba , alfa 1-Antitripsina/sangreRESUMEN
Increased counts and priming of peripheral polymorphonuclear leukocytes (PMNLs) are associated with future or ongoing atherosclerosis; however, the role of PMNLs in enhancing monocyte transendothelial migration is still unclear. Our aims were to examine endothelial and monocyte activation, transmigration, and posttransmigration activation induced ex vivo by in vivo primed PMNLs and the effect of antioxidants on the activation. A unique ex vivo coculture system of three cell types was developed in this study, enabling interactions among the following: primary human umbilical vein endothelial cells (HUVECs), monocytes (THP-1 cell line), and in vivo primed PMNLs from hemodialysis (HD) patients and healthy control (HC) subjects. The interactions among these cells were examined, and an intervention with superoxide dismutase and catalase was performed. Preexposed HUVECs to HD/HC PMNLs showed a significant monocyte transmigration yield, 120-170% above HCs. Monocyte exposure to HD PMNLs induced pre- and posttransmigration activation. When the three cell types were cocultivated at the same time, monocyte chemoattractant protein-1 protein levels released from HUVECs, and activation markers on HUVECs [CD54 and chemokine (C-X3-C motif) ligand 1] and monocytes [chemokine (C-X3-C) receptor 1 and chemokine (C-C motif) receptor 2] were increased. Monocyte transmigration yield decreased to 70% (compared with HC subjects) due to adherence and accumulation of monocytes to HUVECs. When superoxide dismutase and catalase were used, reduced HUVEC and monocyte activation markers brought the transmigration yields to control levels and abolished accumulation of monocytes, emphasizing the role of superoxide in this process. We conclude that peripheral primed PMNLs play a pivotal role in enhancing monocyte transendotelial migration, the hallmark of the atherosclerotic process. Primed PMNLs can be used as a mediator and a biomarker of atherosclerosis even before plaque formation.NEW & NOTEWORTHY Primed polymorphonuclear leukocytes are key mediators in monocyte transendothelial migration, a new understanding of the initiation of endothelial dysfunction and monocyte activation, transmigration, and accumulation in the subendothelial layer.
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Monocitos/fisiología , Neutrófilos/fisiología , Diálisis Renal , Migración Transendotelial y Transepitelial/fisiología , Aterosclerosis/patología , Catalasa/farmacología , Adhesión Celular/fisiología , Quimiocina CCL2 , Técnicas de Cocultivo , Endotelio Vascular , Células Endoteliales de la Vena Umbilical Humana , Humanos , Fallo Renal Crónico/sangre , Activación de Macrófagos , Superóxido Dismutasa/farmacologíaRESUMEN
Hypoalbuminemia of Hemodialysis (HD) patients is an independent cardiovascular risk factor, however, there is no mechanistic explanation between hypoalbuminemia and vascular injury. In the event of oxidative stress and inflammation to which HD patients are exposed, albumin is oxidized and undetected by common laboratory methods, rendering an apparent hypoalbuminemia. We wanted to show that these circulating modified oxidized albumin molecules cause direct vascular damage, mediating inflammation. Once these in-vivo albumin modifications were reduced in- vitro, the apparent hypoalbuminemia concomitantly with its inflammatory effects, were eliminated. Albumin modification profiles from 14 healthy controls (HC) and 14 HD patients were obtained by mass spectrometry (MS) analyses before and after reduction in- vitro, using redox agent 1,4 dithiothreitol (DTT). Their inflammatory effects were explored by exposing human umbilical endothelial cells (HUVEC) to all these forms of albumin. Albumin separated from hypoalbuminemic HD patients increased endothelial mRNA expression of cytokines and adhesion molecules, and augmented secretion of IL-6. This endothelial inflammatory state was almost fully reverted by exposing HUVEC to the in-vitro reduced HD albumin. MS profile of albumin modifications peaks was similar between HD and HC, but the intensities of the various peaks were significantly different. Abolishing the reversible oxidative modifications by DTT prevented endothelial injury and increased albumin levels. The irreversible modifications such as glycation and sulfonation show low intensities in HD albumin profiles and are nearly unobserved in HC. We showed, for the first time, a mechanistic link between hypoalbuminemia and the pro-inflammatory properties of in-vivo oxidized albumin, initiating vascular injury.
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Hipoalbuminemia/sangre , Mediadores de Inflamación/sangre , Albúmina Sérica/metabolismo , Adulto , Anciano , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/genética , Estudios de Casos y Controles , Citocinas/genética , Citocinas/metabolismo , Femenino , Expresión Génica , Células Endoteliales de la Vena Umbilical Humana , Humanos , Hipoalbuminemia/etiología , Hipoalbuminemia/genética , Masculino , Persona de Mediana Edad , Oxidación-Reducción , ARN Mensajero/genética , ARN Mensajero/metabolismo , Diálisis Renal/efectos adversos , Factores de Riesgo , Albúmina Sérica/química , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
INTRODUCTION: Serum levels of ß2-microglobulin (b2M) are significantly higher in patients with end stage renal failure undergoing hemodialysis (HD) and its accumulation accelerates Dialysis Related Amyloidosis (DRA). In HD patients low-flux dialysis, intravenous (IV) iron (administered for the treatment of anemia) affects ß2M removal during dialysis. IV iron also affects the oxidation of plasma proteins, including b2M. AIMS: To examine the effect of intravenous iron therapy on ß2M levels and oxidation in HD patients treated with high-flux compared with low-flux dialyzers. METHODS: Sixteen HD patients on chronic maintenance IV iron therapy were studied. Half of the patients were allocated to high-flux and half to low-flux dialysis. After five weeks, each patient was assigned to the second dialyzer. After two weeks of treatment with each dialyzer, blood samples were taken and serum levels of ß2M were measured. In addition, the hematocrit and iron status were measured. Part of the samples were used to evaluate oxidized ß2M. RESULTS: A significant increase in ß2M levels was found with low-flux dialysis, which further increased during dialysis with IV iron administration. High-flux dialysis therapy significantly lowered the ß2M levels, with a clear decrease during the dialysis session, that was unaffected by IV iron administration. A significant decrease in ß2M oxidation was found during highflux, but not low-flux dialysis. CONCLUSIONS: High-flux dialysis is more effective than lowflux in decreasing the levels and oxidation of ß2M. These observations may have significance in improving iron therapy, aimed to decrease or attenuate the appearance of DRA.
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Células Sanguíneas/metabolismo , Hierro/metabolismo , Fallo Renal Crónico/metabolismo , Diálisis Renal/instrumentación , Microglobulina beta-2/metabolismo , Anemia , Estudios Cruzados , Humanos , Hierro/administración & dosificación , Membranas Artificiales , Diálisis Renal/efectos adversosRESUMEN
BACKGROUND: In clinical states associated with systemic oxidative stress (OS) and inflammation such as chronic kidney disease (CKD), oxidative modifications of serum albumin impair its quantification, resulting in apparent hypoalbuminemia. As the maintenance of oncotic pressure/colloid osmotic pressure (COP) is a major function of albumin, this study examined the impact of albumin oxidation on COP, both in-vivo and in-vitro. METHODS: Patients with proteinuria and patients on chronic hemodialysis (HD) with systemic inflammation and OS were enrolled. Blood samples were collected from 134 subjects: 32 healthy controls (HC), proteinuric patients with high (n = 17) and low (n = 31) systemic inflammation and from 54 patients on chronic hemodialysis (HD) with the highest levels of OS and inflammation. RESULTS: In-vitro oxidized albumin showed significantly higher COP values than non-oxidized albumin at identical albumin levels. In vivo, in hypoalbuminemic HD patients with the highest OS and inflammation, COP values were also higher than expected for the low albumin levels. The contribution to COP by other prevalent plasma proteins, such as fibrinogen and immunoglobulins was negligible. We imply that the calculation of COP based on albumin levels should be revisited in face of OS and inflammation. Hence, in hypoalbuminemic proteinuric patients with systemic OS and inflammation the assumption of low COP should be verified by its measurements.
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Hipoalbuminemia/sangre , Presión Osmótica , Albúmina Sérica , Biomarcadores , Citocinas/metabolismo , Femenino , Fibrinógeno , Humanos , Inmunoglobulinas/sangre , Mediadores de Inflamación/metabolismo , Masculino , Oxidación-Reducción , Estrés Oxidativo , Proteinuria/sangre , Diálisis RenalRESUMEN
OBJECTIVE: Hypoalbuminemia, fluid overload (FO), and oxidative stress (OS) may be related to cardiovascular morbidity and mortality in peritoneal dialysis (PD) patients. OS produces molecular modifications of serum albumin that interfere with its quantification by the commonly used bromocresol green assay. This study evaluated the impact of oxidized serum albumin (OSA) on oncotic pressure (OP) and hydration status. PATIENTS AND METHODS: Twenty-four stable hypoalbuminemic PD patients were enrolled in the study. After performing physical examination, assessment of the hydration status using a whole-body bioimpedance spectroscopy technique was performed, and blood samples were drawn for determination of OP, serum albumin levels, and OSA. RESULTS: Extracellular to total body water (E/TBW) ratio was higher in patients with FO ≥1.5 L with or without edema than in patients with FO <1.5 L (P≤0.043). E/TBW ratio was higher in patients with FO ≥1.5 L and edema compared to those with FO ≥1.5 L but without edema (P=0.004). OP was significantly higher in patients with FO ≥1.5 L and without edema compared to those with FO ≥1.5 L and with edema (P<0.001). Albumin-detection index (ADI) in patients with FO ≥1.5 L and without edema was similar to ADI in patients with FO <1.5 L (P=0.520). ADI was significantly lower in patients with FO ≥1.5 L and without edema compared to those with FO ≥1.5 L and edema (P=0.034). E/TBW ratio correlated positively with the ADI (r=0.60, P=0.001) and inversely with the OP (r=-0.54, P=0.002). CONCLUSION: Overhydration may be clinically undetectable in PD patients. Assessing the hydration status and measuring the total serum albumin levels, including the oxidized fraction, should be considered in evaluating hydration status in PD patients.
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AIM: Contrast-induced-nephropathy (CIN) is associated with poor outcomes, thus prevention of CIN may be of clinical value. Erythropoietin (EPO) has been shown to elicit tissue-protective effects in experimental models and in clinical studies of acute kidney injury. We therefore evaluated its effectiveness for prevention of CIN after coronary angiography (CA) ± percutaneous coronary intervention (PCI) in diabetic patients with chronic kidney disease. METHODS: A prospective, randomized, controlled trial was carried out in 138 diabetic patients with eGFR <60 mL/min who underwent non-urgent CA ± PCI. Patients received normal saline and n-acetyl cysteine before CA, with or without 50,000 U of EPO administered 30 min prior to CA. CIN was defined as an increase in serum creatinine of at least 0.5 mg/dL during the first 2 days after exposure to contrast media. Primary outcome was the incidence of CIN. Secondary outcomes were the sensitivity and positive predictive value (PPV) of Cystatin C (CC) and Neutrophil-gelatinase-associated-lipocalin (NGAL) for diagnosis of CIN. RESULTS: The observed incidence of CIN was 8.7%, significantly lower than the expected for such high-risk population. The administration of EPO prior to CA did not reduce the incidence of CIN (9.7% vs. 7.6%, P = 0.65). CC and NGAL demonstrated a low sensitivity (16.6%) and low PPV (6.7 and 33.3%, respectively) for detecting CIN. CONCLUSION: The administration of EPO prior to CA did not reduce the incidence of CIN. Additional prospective research with a larger sample size and in other patient categories is essential to further define the potential protective effect of EPO on prevention of CIN.
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Lesión Renal Aguda/prevención & control , Medios de Contraste/efectos adversos , Angiografía Coronaria/efectos adversos , Nefropatías Diabéticas/tratamiento farmacológico , Eritropoyetina/administración & dosificación , Yohexol/análogos & derivados , Sustancias Protectoras/administración & dosificación , Insuficiencia Renal Crónica/tratamiento farmacológico , Ácidos Triyodobenzoicos/efectos adversos , Acetilcisteína/administración & dosificación , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/diagnóstico , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Biomarcadores/orina , Cistatina C/sangre , Citoprotección , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/diagnóstico , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Infusiones Intravenosas , Yohexol/efectos adversos , Israel , Lipocalina 2/orina , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Proteínas Recombinantes/administración & dosificación , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Patients with severe or progressive idiopathic membranous nephropathy (IMN) should receive immunosuppressive therapy (IST). Alkylating agents, corticosteroids and cyclosporine A (CsA) may be associated with substantial adverse effects and high relapse rates. To determine whether CsA is effective for long-term remission in the treatment of IMN with moderate to high risk for progression to renal failure, when given in a dosage of 3.5 mg/kg/day for 18 months, then tapered gradually to a maintenance dose of 0.35-0.70 mg/kg/day within 6 months and continued for 5.5 years. METHODS: The long-term effectiveness of our CsA regimen in 33 incident nephrotic IMN patients was determined retrospectively. Daily proteinuria, serum albumin and creatinine clearance were compared before starting therapy (time 0) and at 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 years. RESULTS: At the end of 18 months, 84.8% of patients treated with CsA were in remission; 78.8% maintained long-term remission for 10 years. All patients with complete remission (CR), 75% of those with partial remission (PR), 20% of non-responders (NR) and 14.3% of those who were treated with NIST, were free of chronic kidney disease (CKD) stage 3 at 10 years (P<0.001). Reduction in daily proteinuria by ≥50% at 6 months was the most powerful predictor for achievement of CR or PR (P=0.02). CONCLUSIONS: For most patients, CsA was effective in achieving sustained long-term remission without relapses, when gradually tapered to low maintenance dose given for 5.5 years.
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Ciclosporina/uso terapéutico , Glomerulonefritis Membranosa/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Adulto , Anciano , Ciclosporina/administración & dosificación , Femenino , Humanos , Inmunosupresores/administración & dosificación , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/prevención & control , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Heparin is known to have anti-inflammatory effects, yet the mechanisms are not completely understood. In this study, we tested the hypothesis that heparin has a direct effect on activated polymorphonuclear leukocytes (PMNLs), changing their activation state, and can explain its anti-inflammatory effect. To test our hypothesis, we designed both in vitro and ex vivo studies to elucidate the mechanism by which heparin modulates PMNL functions and therefore the inflammatory response. We specifically tested the hypothesis that priming of PMNLs renders them more susceptible to heparin. Amplified levels of CD11b and increased rate of superoxide release manifested PMNL priming. Increase in cell priming resulted in a dose-dependent increase in heparin binding to PMNLs followed by augmented apoptosis. Blocking antibodies to CD11b inhibited heparin binding and abolished the apoptotic response. Moreover, heparin caused a significant dose-dependent decrease in the rate of superoxide release from PMNLs, which was blunted by blocking antibodies to CD11b. Altogether, this study shows that the interaction of heparin with the PMNL CD11b results in cell apoptosis and explains heparin's anti-inflammatory effects.
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Antiinflamatorios/farmacología , Antígeno CD11b/metabolismo , Heparina/farmacología , Inflamación/inmunología , Neutrófilos/efectos de los fármacos , Anticuerpos Bloqueadores/farmacología , Apoptosis/efectos de los fármacos , Antígeno CD11b/inmunología , Células Cultivadas , Humanos , Activación de Linfocitos/efectos de los fármacos , Neutrófilos/inmunología , Unión Proteica/efectos de los fármacos , Superóxidos/metabolismoRESUMEN
AIMS: To test the hypothesis that primed PMNLs in blood of chronic kidney disease patients release the active form of elastase and cathepsin G causing degradation of vital proteins and promote tissue damage. METHODS: RT-PCR, immunocytochemical staining, immunoblotting, and FACS analyses were used to study these enzymes in hemodialysis patients (HD) versus healthy normal controls (NC). Using PMNLs and endothelial cells cocultivation system we measure the effect of HD PMNLs on the endothelial VE-cadherin, an essential protein for maintaining endothelial integrity. RESULTS: Levels of elastase and cathepsin G were reduced in PMNLs of HD patients, while mRNA enzymes levels were not different. Elevated levels of the active form of these enzymes were found in blood of HD patients compared to NC.HD plasma had higher levels of soluble VE-cadherin present in three molecular forms: whole 140 kDa molecule and two fragments of 100 and 40 kDa. Cocultivation studies showed that primed PMNLs cleave the endothelial cadherin, resulting in a 100 kDa fragment. CONCLUSIONS: Elastase and cathepsin G are elevated in the plasma of HD patients, originating from primed PMNLs. In these patients, chronic elevation of these enzymes contributes to cleavage of VE-cadherin and possible disruption of endothelial integrity.
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Antígenos CD/metabolismo , Cadherinas/metabolismo , Catepsina G/metabolismo , Endotelio Vascular/metabolismo , Leucocitos/metabolismo , Elastasa Pancreática/metabolismo , Diálisis Renal , Adulto , Endotelio Vascular/lesiones , Endotelio Vascular/patología , Activación Enzimática , Femenino , Humanos , Leucocitos/patología , Masculino , Persona de Mediana Edad , ARN Mensajero/metabolismoRESUMEN
BACKGROUND: Atherosclerotic cardiovascular disease (CVD) is the most common cause of morbidity and mortality among hemodialysis (HD) patients. It has been attributed, among other causes, to hypertension and dyslipidemia. The aim of the present study was to investigate the effect of a year-long consumption of Pomegranate juice (PJ), on two traditional cardiovascular (CV) risk factors: hypertension and lipid profile, as well as on cardiovascular events. METHODS: 101 HD patients were randomized to receive 100 cc of PJ (0.7 mM polyphenols) or matching placebo juice, three times a week for one year. The primary endpoints were traditional CV risk factors; blood pressure and lipid profile. Systolic, diastolic and pulse pressure, plasma levels of triglycerides (TG), high density lipoprotein (HDL), low density lipoprotein (LDL) and total cholesterol were monitored quarterly during the study year. Secondary endpoint was incidence of cardiovascular events. RESULTS: PJ consumption yielded a significant time response improvement in systolic blood pressure, pulse pressure, triglycerides and HDL level; an improvement that was not observed in the placebo intake group. These beneficial outcomes were more pronounced among patients with hypertension, high level of triglycerides and low levels of HDL. CONCLUSION: Regular PJ consumption by HD patients reduced systolic blood pressure and improved lipid profile. These favorable changes may reduce the accelerated atherosclerosis and high incidence of CVD among HD patients. TRIAL REGISTRATION: ClinicalTrials.gov registry, Identifier number: NCT00727519.
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Bebidas , Enfermedades Cardiovasculares/prevención & control , Lípidos/sangre , Lythraceae , Fitoterapia , Preparaciones de Plantas/uso terapéutico , Adulto , Anciano , Aterosclerosis/prevención & control , Presión Sanguínea/efectos de los fármacos , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Femenino , Humanos , Hipertensión/prevención & control , Masculino , Persona de Mediana Edad , Placebos , Diálisis Renal , Factores de Riesgo , TriglicéridosRESUMEN
The hemodialysis (HD) procedure induces oxidative stress (OS), which is further aggravated by intravenous (IV) iron administration, aimed at correcting anemia of patients with HD. We have recently shown that 1 year of pomegranate juice (PJ) intake attenuated OS and inflammation in patients with HD. In the current study, we hypothesized that a single dose of PJ can attenuate the enhanced OS and inflammation induced by both the dialysis procedure and IV iron administration during HD session. Twenty-seven patients with HD were randomized to receive PJ or placebo during 1 dialysis session with IV iron. Blood samples were drawn before and after the session to asses OS biomarkers such as advanced oxidation protein products and myeloperoxidase (MPO), whereas polymorphonuclear leukocyte (PMNL) counts served as an indirect measure of inflammation. At the end of the dialysis session, an increase in advanced oxidation protein products and MPO levels as well as a decrease in PMNLs counts were observed in the placebo group, whereas no significant changes occurred in the PJ group. The postdialysis increase in MPO levels in the placebo group is a direct result of PMNL degranulation, associated with postdialysis decrease in PMNL counts. Degranulation of PMNLs leads to the release of other cell moieties, such as inflammatory mediators and proteases that enhance inflammation. We conclude that PJ intake attenuated the increase in systemic OS and inflammation induced by IV iron administration during the dialysis session. These beneficial effects illuminate the previously observed attenuation in OS and inflammation in patients with HD on prolonged PJ intake.
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Bebidas , Hierro/efectos adversos , Lythraceae/química , Estrés Oxidativo/efectos de los fármacos , Diálisis Renal/efectos adversos , Administración Intravenosa , Anciano , Anemia/tratamiento farmacológico , Biomarcadores/sangre , Relación Dosis-Respuesta a Droga , Femenino , Frutas/química , Humanos , Inflamación/tratamiento farmacológico , Inflamación/etiología , Hierro/administración & dosificación , Fallo Renal Crónico/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Neutrófilos/metabolismo , Peroxidasa/metabolismoRESUMEN
Previous studies suggest that oxidative modifications of serum albumin lead to underestimation of albumin concentrations using conventional assays. In addition, oxidation of serum albumin may cause neutrophil activation and further oxidation of albumin, which may result in a series of reciprocal cyclical processes. Because hypoalbuminemia, systemic inflammation, and oxidative stress are common in diabetic nephropathy patients, the aim of this study was to show that albumin modifications and neutrophil activation underlie these reciprocal systemic processes. Blood samples from a cohort of 19 patients with diabetic nephropathy and 15 healthy controls were used for albumin separation. An oxidation-dependent "albumin detection index," representing the detection efficacy of the universal bromocresol green assay, was determined for each subject. This index was correlated with serum albumin levels, various markers of oxidative stress or inflammation, and kidney function. Activation of separated neutrophils by glycoxidized albumin was assessed by the release of neutrophil gelatinase-associated lipocalin (NGAL) and myeloperoxidase (MPO). The albumin detection index of diabetic nephropathy patients was significantly lower compared to that of controls, correlating positively with serum levels of albumin and kidney function and negatively with albumin glycoxidation and inflammatory markers. Glycoxidized albumin had a direct role in neutrophil activation, resulting in NGAL and MPO release. The hypoalbuminemia observed in patients with diabetic nephropathy partially results from underestimation of modified/oxidized albumin using the bromocresol green assay. However, modified or oxidized albumin may lead to a cycle of accelerated oxidative stress and inflammation involving neutrophil activation. We suggest that the albumin detection index, a new marker of oxidative stress, may also serve as a biomarker of diabetic nephropathy severity and its progression.
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Nefropatías Diabéticas/sangre , Activación Neutrófila , Oxidación-Reducción , Albúmina Sérica/metabolismo , Adulto , Anciano , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/metabolismo , Femenino , Humanos , Hipoalbuminemia/sangre , Hipoalbuminemia/metabolismo , Masculino , Persona de Mediana Edad , Neutrófilos/metabolismoRESUMEN
Increased systemic inflammation and oxidative stress are well established as nontraditional key players in the pathogenesis of atherosclerosis and are also involved in the innate immunity dysregulation in hemodialysis (HD) patients. The study aim was to investigate the effect of 1-year intake of pomegranate juice, an antioxidant source, on oxidative stress, inflammation, and long-term clinical outcomes. A randomized placebo controlled double-blind trial was designed, enrolling 101 chronic HD patients to receive during each dialysis 100 cc of pomegranate juice, or matching placebo, three times a week for 1 year. The primary endpoints were levels of oxidative stress and inflammation biomarkers. Secondary endpoints were hospitalization due to infections and the progression of atherosclerotic process based on a composite of variables of the carotid arteries: intima media thickness (IMT), number, and structure of plaques. Pomegranate juice intake yielded a significant time response reduction in polymorphonuclear leukocyte priming, protein oxidation, lipid oxidation, and inflammation biomarkers levels. These beneficial effects were abolished 3 months postintervention. Pomegranate juice intake resulted in a significantly lower incidence rate of the second hospitalization due to infections. Furthermore, 25% of the patients in the pomegranate juice group had improvement and only 5% progression in the atherosclerotic process, while more than 50% of patients in the placebo group showed progression and none showed any improvement. Prolonged pomegranate juice intake improves nontraditional CV risk factors, attenuates the progression of the atherosclerotic process, strengthens the innate immunity, and thus reduces morbidity among HD patients.
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Antioxidantes/administración & dosificación , Aterosclerosis/tratamiento farmacológico , Infecciones Bacterianas/prevención & control , Arterias Carótidas/efectos de los fármacos , Lythraceae , Fitoterapia/métodos , Anciano , Anciano de 80 o más Años , Aterosclerosis/patología , Infecciones Bacterianas/epidemiología , Bebidas , Biomarcadores/análisis , Arterias Carótidas/patología , Grosor Intima-Media Carotídeo , Método Doble Ciego , Femenino , Humanos , Incidencia , Inflamación/tratamiento farmacológico , Inflamación/patología , Peroxidación de Lípido/efectos de los fármacos , Masculino , Persona de Mediana Edad , Estrés Oxidativo/efectos de los fármacos , Placa Aterosclerótica/tratamiento farmacológico , Placa Aterosclerótica/patología , Diálisis Renal , Resultado del TratamientoRESUMEN
BACKGROUND: Hypoalbuminemia is a measure of malnutrition, inflammation and a predictor of mortality in uremia. It is controversial whether albumin levels per se are associated with the clinical outcomes in uremic patients. The co-occurrence of hypoalbuminemia and oxidative stress in hemodialysis (HD) patients led us to hypothesize that oxidative modifications of albumin decrease its detection and influence albumin quantification. METHODS: Albumin levels are determined in clinical laboratories mainly by the bromocresol green (BCG) spectrophotometric assay. The detection of serum albumin was investigated in HD patients and in healthy controls using an "albumin-detection index", defined as the ratio between BCG read-out (albumin-specific) to total albumin. The detection efficacy of albumin was also investigated in vitro, after glycoxidation, HOCl-mediated-oxidation, and metal-catalyzed-oxidation. Oncotic pressure was measured to assess albumin function. RESULTS: The albumin-detection index of patients was significantly lower compared with controls, correlating negatively with oxidative stress markers (serum advanced oxidation protein products-AOPP and glycoxidized serum albumin) and positively with serum albumin levels. The albumin-detection index was also decreased after in vitro oxidation. CONCLUSIONS: The study shows, both in vivo and in vitro, decreased detection of oxidized albumin by a commonly-used clinical assay, thus providing the molecular link between oxidative stress and hypoalbuminemia. Oxidative stress as reflected by hypoalbuminemia, rather than actual albumin levels, may be related to cardiovascular morbidity outcomes in HD patient.
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Albuminuria/sangre , Enfermedades Cardiovasculares/etiología , Estrés Oxidativo , Diálisis Renal/efectos adversos , Albúmina Sérica/análisis , Albúmina Sérica/metabolismo , Adulto , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oxidación-Reducción , Conformación Proteica , Albúmina Sérica/químicaRESUMEN
BACKGROUND: The effect of acute kidney injury (AKI) on anemia has been well-documented. However, the effect of 'preexisting' anemia on AKI has been less addressed. The aims of the present study were to investigate (1) the association between anemia at hospital admission and AKI occurrence, and (2) the effect of 'preexisting' anemia on the clinical outcomes of AKI. METHODS: A retrospective cohort study was undertaken among patients aged > or =17 years who were admitted to our hospital during the year 2006 (n = 34,802). Anemia at hospital admission and AKI occurrences were determined using the WHO definition and the RIFLE criteria, respectively. A subgroup of patients with an estimated glomerular filtration rate > or =60 ml/min/1.73 m(2) was analyzed separately to control for the effect of chronic kidney disease on anemia. RESULTS: The cumulative incidence of AKI was 11.2% in anemic patients at hospital admission, compared to 5.5% in nonanemic subjects. The association between anemia at admission and AKI occurrence remained statistically significant after controlling for potential confounders (odds ratio 1.5, 95% CI 1.4-1.6). In addition, an association between anemia at hospital admission and clinical outcomes of AKI was observed. CONCLUSION: Anemia at hospital admission should be recognized as a potential risk factor for in-hospital AKI occurrence.
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Lesión Renal Aguda/sangre , Lesión Renal Aguda/etiología , Anemia/sangre , Anemia/complicaciones , Admisión del Paciente/tendencias , Lesión Renal Aguda/mortalidad , Adulto , Anciano , Anemia/mortalidad , Estudios de Cohortes , Femenino , Hemoglobinas/metabolismo , Mortalidad Hospitalaria/tendencias , Hospitalización/tendencias , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
In the Sabra rat, oxidative stress (OS) and inflammation precede the development of hypertension. Inhibition of the phagocytic NADPH oxidase attenuates the rise in blood pressure. The present study was set to identify possible priming agents for this enzyme and to test the hypothesis that the phagocytic NADPH oxidase contributes to OS and inflammation. Sabra salt-sensitive and Sabra salt-resistant rats were salt loaded or provided regular chow for 60 days with or without apocynin to inhibit NADPH oxidase. Levels of interleukin 6, tumor necrosis factor-alpha, and interferon-gamma served as indices of inflammation. Extracellular and intracellular levels of the polymorphonuclear leukocyte tumor necrosis factor-alpha receptors (p55 and p75) were assessed by flow cytometry in young and adult rats. NADPH oxidase activity and expression of p47phox were measured in polymorphonuclear leukocytes and aortic rings. Malondialdehyde and carbonylated fibrinogen served as indices of OS. Inflammatory and OS indices excluding interferon-gamma were higher in the hypertensive state and reduced by apocynin. Levels of malondialdehyde and tumor necrosis factor-alpha were elevated already in the prehypertensive state. No differences were found in the levels of p75. The extracellular expression of p55 was higher in adult Sabra salt-resistant compared with Sabra salt-sensitive rats (7.46+/-2.2% versus 2.1+/-0.5%; P<0.05), whereas levels of the intracellular p55 were higher in adult Sabra salt-sensitive rats (3.2+/-2% versus 1.1+/-0.5%; P<0.05). In young normotensive rats, the extracellular levels of p55 were higher in Sabra salt-sensitive compared with Sabra salt-resistant rats (10.6+/-5.2% versus 2.9+/-1.5%; P<0.01). Tumor necrosis factor-alpha plays a role in activation of the polymorphonuclear leukocyte NADPH oxidase, thereby contributing to systemic OS, inflammation, and the development of hypertension in this model.