Najla Elias Farage

Effect of Brazil nut supplementation on the blood levels of selenium and glutathione peroxidase in hemodialysis patients

OBJECTIVE In patients who have undergone hemodialysis, large amounts of reactive oxygen species (ROS) are produced and, at higher concentrations, ROS are thought to be involved in the pathogenesis of cardiovascular disease. It has been proposed that selenium (Se) may exert an antiatherogenic influence by reducing oxidative stress. The richest known food source of selenium is the Brazil nut (Bertholletia excelsa, family Lecythidaceae), found in the Amazon region. We evaluated the effect of Brazil nut supplementation on blood levels of Se and glutathione peroxidase (GSH-Px) activity in patients on hemodialysis. METHODS A total of 81 patients on hemodialysis (52.0±15.2 y old, average time on dialysis 82.3±91.4 mo, body mass index 24.9±4.4 kg/m(2)) from the RenalCor and RenalVida Clinics in Rio de Janeiro, Brazil, were studied. All patients received one nut (around 5 g, averaging 58.1 μg Se/g) a day for 3 mo. The Se concentrations in the nuts and in plasma and erythrocytes were determined by atomic absorption spectrophotometry with hydride generation (Hitachi, Z-500). GSH-Px levels were measured using Randox commercial kits. RESULTS Plasma Se (18.8±17.4 μg/L) and erythrocyte (72.4±37.9 μg/L) levels were below the normal range before nut supplementation. After supplementation, the plasma level increased to 104.0±65.0 μg/L and erythrocytes to 244.1±119.5 μg/L (P<0.0001). The activity of GSH-Px also increased after supplementation, from 46.6±14.9 to 55.9±23.6 U/g of hemoglobin (P<0.0001). Before supplementation, 11% of patients had GSH-Px activity below the normal range (27.5-73.6 U/g of hemoglobin). After supplementation, all patients showed GSH-Px activity within the normal range. CONCLUSION The data revealed that the investigated patients presented Se deficiency and that the consumption of only one Brazil nut a day (5 g) during 3 mo was effective to increase the Se concentration and GSH-Px activity in these patients, thus improving their antioxidant status.

Is a body mass index of 23 kg/m2 a reliable marker of protein–energy wasting in hemodialysis patients?

OBJECTIVE To evaluate the body composition and inflammatory status in patients on hemodialysis (HD) according to the cutoff of 23 kg/m² for the body mass index (BMI). METHODS Forty-seven patients (30 men, 11 diabetics, 53.8 ± 12.2 y of age, 58.2 ± 50.9 mo on HD) were studied. Anthropometric data and handgrip strength were evaluated. C-reactive protein, tumor necrosis factor-α, leptin, and interleukin-6 were measured. Mortality was assessed after 24 mo of follow-up. RESULTS Nineteen patients (40.4%) presented BMI values lower than 23 kg/m² and leptin levels, midarm muscle area, and free-fat mass were significantly lower in these patients. The prevalence of functional muscle loss according to handgrip strength was not different between the BMI groups. The sum of skinfold thicknesses, the percentage of body fat, fat mass, the fat mass/free-fat mass ratio, and waist circumference were significantly lower in patients with a BMI lower than 23 kg/m², but the mean values did not indicate energy wasting. Patients with a BMI higher than 23 kg/m² presented a higher prevalence of inflammation and higher waist circumference and body fat values. The adiposity parameters were correlated with C-reactive protein and leptin. A Cox multivariate regression analysis demonstrated that C-reactive protein, tumor necrosis factor-α, and interleukin-6 predict cardiovascular mortality. CONCLUSION Patients on HD with a BMI lower than 23 kg/m² did not present signs of energy wasting, whereas those with a BMI higher than 23 kg/m² had more inflammation, probably because of a greater adiposity. Thus, the BMI value of 23 kg/m² does not seem to be a reliable marker of protein-energy wasting in patients on HD.

Is zinc-α2-glycoprotein a cardiovascular protective factor for patients undergoing hemodialysis?

BACKGROUND Zinc-α2-glycoprotein (ZAG) is a lipid mobilizing factor. Its anti-inflammatory action and expression pattern suggest that ZAG could act by protecting against the obesity-associated disorders. In hemodialysis (HD) patients, ZAG levels were described to be elevated but its effects on markers of inflammation and LDL oxidation are still unclear. We investigated the relationship between ZAG and markers of systemic inflammation and LDL atherogenic modification profile in HD patients. METHODS Forty-three patients regularly on HD were studied and compared to 20 healthy subjects. Plasma ZAG, adiponectin, electronegative LDL [LDL(-)], an atherosclerotic negatively charged LDL subfraction, and anti-LDL(-) autoantibodies levels were measured by ELISA. Markers of inflammation and atherogenic cell recruitment (TNF-α, interleukin-6, VCAM-1, ICAM-1, MCP-1 and PAI-1) were also determined. RESULTS Inflammatory markers and atherogenic cell recruitment were higher in HD patients when compared to healthy subjects. ZAG levels were also higher in HD patients (151.5 ± 50.1 mg/l vs 54.6 ± 23.0 mg/l; p<0.0001) and its levels were negatively correlated with TNF-α (r=-0.39; p=0.001) and VCAM-1 (r=-0.52; p<0.0001) and, positively correlated with anti-LDL(-) autoantibodies (r=0.38; p=0.016). On multivariate analyses, plasma ZAG levels were independently associated with VCAM-1 (p=0.01). CONCLUSION ZAG is inversely associated with markers of pro-atherogenic factors linked to systemic inflammation and oxidative stress. Thus, this adipokine may constitute a novel marker of a favorable metabolic profile regarding cardiovascular risk factors in HD population.

Underreporting of Energy Intake in Maintenance Hemodialysis Patients: A Cross-sectional Study

OBJECTIVE To analyze the reported energy intake (EI(rep)) in hemodialysis (HD) patients by total energy expenditure (TEE) measured by a dedicated device. DESIGN Cross-sectional study. SETTING RenalCor and RenalVida Clinics (Rio de Janeiro, Brazil). PATIENTS AND OTHERS PARTICIPANTS Forty-eight HD patients (51.4 ± 12.2 years, 62% men, body mass index [BMI], 23.8 ± 4.5 kg/m(2)) were studied. MAIN OUTCOME MEASURE EI(rep) was evaluated using a 3-day food record. TEE was measured over a 2-day period by SWA (SenseWear Pro2 Armband, BodyMedia Inc., Pittsburgh, PA). Subjects were identified as underreporters (URs), acceptable reporters (ARs), or overreporters (ORs) from their EI(rep)/TEE ratio. ARs were defined as having the EI(rep)/TEE ratio in the range of 0.76 to 1.24, URs as EI(rep)/TEE <0.76, ORs as EI(rep)/TEE >1.24 according to Goldberg index. RESULTS The mean TEE and EI(rep) were 34.7 ± 9.4 kcal/kg/day and 22.8 ± 10.6 kcal/kg/day, respectively, and 37.5% of patients presented overweight or obesity. Thirty-one patients (65%) were identified as URs, and the mean of Goldberg index was 0.54 ± 0.12 (0.23 to 0.75), versus 0.95 ± 0.12 (0.79 to 1.2) for ARs. There were no ORs among the patients studied. There were negative correlations between Goldberg index and BMI (r = -0.35, P < .01) and % body fat (r = -0.4, P < .01) and between EI(rep) and BMI (r = -0.58, P < .001). CONCLUSION These results confirm a high prevalence of underreporting of EI in HD patients, particularly in patients with high BMI.

Apelin: A Peptide Involved in Cardiovascular Risk in Hemodialysis Patients?

Inflammation, oxidative stress, and obesity are important features associated with pathogenesis of cardiovascular disease, a major contributor to the mortality of hemodialysis (HD) patients. Apelin is an adipokine involved in a variety of physiological functions; however, little is known about apelin in chronic kidney disease (CKD). Thus, the purpose of this study was to analyze apelin plasma levels in HD patients and verify whether there is any relationship with inflammation, oxidative markers, and obesity. Twenty-four HD patients [53.6 ± 14.4 years, 14 men, and body mass index (BMI) of 25.0 ± 4.2 kg/m2] were studied and compared with 15 healthy subjects (51.3 ± 13.5 years, 7 men, and BMI of 26.3 ± 3.7 kg/m2). Plasma apelin-12 and -36 were measured using the enzyme immunometric assay method. Plasma electronegative low-density lipoprotein [LDL(–)] levels were measured using ELISA method, and tumor necrosis factor-α, interleukin-6, leptin, and plasminogen activator inhibitor-1 levels were measured by a multiplex assay kit. C-Reactive protein (CRP) was determined by immunoturbidimetry. Anthropometric data were also evaluated. There was no difference between apelin-36 levels in HD patients (0.82 ± 0.60 ng/mL) and healthy subjects (0.83 ± 0.23 ng/mL). In contrast, apelin-12 levels were significantly higher in patients (0.34 ± 0.15 ng/mL vs. 0.24 ± 0.13 ng/mL in healthy subjects). TNF-α, CRP, and LDL(–) levels were higher in patients; however, there was no correlation among apelin-12 or -36 and inflammatory or oxidative markers. The adiposity parameters were also not associated with apelin-12 or -36. In conclusion, plasma apelin seems to be not associated with cardiovascular risk in HD patients.

Effect of Brazil Nut Supplementation on Plasma Levels of Selenium in Hemodialysis Patients: 12 Months of Follow-up

BACKGROUND Large amounts of reactive oxygen species are produced in hemodialysis (HD) patients, and, at higher concentrations, reactive oxygen species are thought to be involved in the pathogenesis of cardiovascular disease. It has been proposed that selenium (Se) may exert an antiatherogenic influence by reducing oxidative stress. The richest known food source of Se is the Brazil nut (Bertholletia excelsa, family Lecythidaceae), found in the Amazon region. OBJECTIVE The objective of this work was to determine if Se plasma levels in HD patients submitted to a program of supplementation during 3 months with 1 Brazil nut by day could be sustained after 12 months. METHODS A total of 21 HD patients (54.2 ± 15.2 years old; average time on dialysis, 82.3 ± 51.6 months; body mass index, 24.4 ± 3.8 kg/m(2)) from the RenalCor Clinic in Rio de Janeiro, Brazil, were followed up 12 months after the supplementation study ended. The Se plasma levels were determined by atomic absorption spectrophotometry with hydride generation. RESULTS The Se Plasma levels (17.3 ± 19.9 μg/L) were below the normal range (60 to 120 μg/L) before nut supplementation, and after 3 months of supplementation, the levels increased to 106.8 ± 50.3 μg/L (P < .0001). Twelve months after supplementation, the plasma Se levels decreased to 31.9 ± 14.8 μg/L (P < .0001). CONCLUSIONS The data showed that these patients were Se deficient and that the consumption of Brazil nut was effective to increase the Se parameters of nutritional status. Se levels 12 months after the supplementation period were not as low as presupplementation levels but yet significantly lower, and we needed to motivate patients to adopt different dietary intake patterns.

Increased electronegative LDL and decreased antibodies against electronegative LDL levels correlate with inflammatory markers and adhesion molecules in hemodialysed patients.

BACKGROUND Chronic Kidney Disease (CKD) patients present high levels of electronegative LDL (LDL-) that can modulate the expression of molecules involved in inflammation and it is closely linked to atherosclerosis. We investigated the association between LDL(-) and inflammatory markers in patients undergoing hemodialysis (HD). METHODS Forty-seven HD patients from a private clinic in Rio de Janeiro, Brazil were studied and compared with 20 age matched healthy individuals. Serum LDL(-) and anti-LDL(-) autoantibody levels were measured by ELISA; TNF-α, IL-6, VCAM-1 and ICAM-1 were determined by a multiplex assay kit. RESULTS HD patients presented higher IL-6 and TNF-α concentrations (4.1 ± 1.6 and 5.5 ± 2.1 pg/ml, respectively) than healthy subjects (2.6 ± 0.2 and 2.4 ± 1.1 pg/ml, respectively) (p=0.0001). In addition, they presented higher VCAM-1 and ICAM-1 levels and, LDL(-) concentrations were also increased (0.18 ± 0.12 U/l) when compared to healthy individuals (0.10 ± 0.08 U/l) (p<0.02). In contrast, the anti-LDL(-) autoantibody levels were lower in HD patients (0.02 ± 0.01 mg/l) than in healthy subjects (0.05 ± 0.03 mg/l) (p<0.001). There was a positive correlation between LDL(-) and IL-6 (r=0.25, p=0.004) and ICAM-1 (r=0.36; p=0.003). There was also a negative correlation between anti-LDL(-) autoantibodies and TNF-α (r=-0.37; p=0.003) and VCAM-1 (r=-0.50; p=0.0001). CONCLUSIONS The association between LDL(-) and inflammation and the lower levels of anti-LDL(-) autoantibodies are important risk factors related to atherosclerosis in CKD.

Reduced Plasma Zinc Levels, Lipid Peroxidation, and Inflammation Biomarkers Levels in Hemodialysis Patients: Implications to Cardiovascular Mortality

Despite the fact that low plasma zinc (Zn) levels play important roles in the oxidative stress, the relationships between lipid peroxidation and inflammation biomarkers with low plasma Zn levels have not been investigated in chronic kidney disease (CKD) patients. The aim of this study was to evaluate the Zn plasma levels, electronegative LDL [LDL(–)] levels, and inflammation markers as predictors of cardiovascular (CV) mortality in hemodialysis (HD) patients. Forty-five HD patients (28 men, 54.2 ± 12.7 years, 62.2 ± 51.4 months on dialysis and BMI 24.3 ± 4.1 kg/m2) were studied and compared to 20 healthy individuals (9 men, 51.6 ± 15.6 years, BMI 25.2 ± 3.9 kg/m2) and followed for 24 months to investigate the risks for CV mortality. LDL(–) levels were measured by ELISA, plasma Zn levels by atomic absorption spectrophotometry, C-reactive protein (CRP) level by immunoturbidimetric method, and tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and plasminogen activator inhibitor-1 (PAI-1) levels by a multiplex assay kit. HD patients presented low plasma Zn levels (54.9 ± 16.1 μg/dL) and high-LDL(–) (0.18 ± 0.12 U/L) and TNF-α (5.5 ± 2.2 pg/mL) levels when compared to healthy subjects (78.8 ± 9.4μ g/dL, 0.10 ± 0.08U/L, 2.4 ± 1.1 pg/mL, respectively, p < 0.05). Zn plasma levels were negatively correlated to TNF-α (r = –0.49; p = 0.0001) and LDL(–) (r = –0.33; p = 0.008). During the 2 years, 24.4% of the patients died, all due to CV disease. Analysis by the Cox model showed that high CRP, TNF-α, IL-6 levels, and long duration of HD were significant predictors of mortality. In conclusion, reduced Zn levels were associated with lipid peroxidation and inflammation, and we confirm here in a Brazilian cohort of HD patients that inflammation markers are strong predictors of CV death.

Zinc-α2-Glycoprotein: Is There Association between This New Adipokine and Body Composition in Hemodialysis Patients?

Peptides involved in the regulation of body composition are of interest in hemodialysis (HD) patients because protein wasting associated with high fat mass (FM) is present in these patients. Zinc-α2-glycoprotein (ZAG), a new adipokine, is involved in the regulation of lipid metabolism, adiposity, and energy balance. The purpose of this study was to evaluate ZAG levels and its relationship with body composition and dietary intake in HD patients. Forty-nine HD patients (28 men, 53.1 ± 12.5 years, and BMI 24.0 ± 4.3 kg/m2) were studied and compared with 20 healthy subjects (9 men, 49.5 ± 15.2 years, and BMI 25.6 ± 4.1 kg/m2). Plasma ZAG levels were measured using the ELISA methods and body composition was evaluated through anthropometric data. Dietary intake was assessed 3 days by 24-hour food recall. Although most of the HD patients (59.2%) were eutrophic according to BMI, 92.3% presented high percentage of body fat (BF), and 43.5%, reduced fat-free mass according to midarm muscle circumference values. ZAG levels were ∼2.5-fold higher in HD patients (135.9 ± 40.9 mg/L) compared with healthy individuals (54.6 ± 23.0 mg/L) (p < 0.0001). Circulating ZAG was not associated with dietary intake; however, this peptide was negatively correlated with %BF and, for each 1% reduction in BF, ZAG levels increased by 2.4 mg/L (p = 0.02). In summary, circulating ZAG is increased and inversely correlated with adiposity in HD patients; however, in spite of its higher plasma levels, the majority of HD patients did not show low BF.

The Relationship between Apelin and Parathyroid Hormone in Hemodialysis Patients

Both apelin and parathyroid hormone (PTH) are endogenous ligands for G-protein-coupled receptors. Apelin acts as a mitogenic agent for osteoblasts, and metabolic bone abnormalities are frequently seen in hemodialysis (HD) patients because of hyperparathyroidism. The aim of this study was to analyze plasma apelin levels in HD patients and to determine whether they are related to PTH concentrations. A total of 23 HD patients [15 men and 8 women, with a mean (SD) age of 54.2 (4.4) years and a mean body mass index (BMI) of 25.0 (4.1) kg/m2] were studied and compared with 15 healthy subjects [6 men and 9 women, with a mean (SD) age of 51.3 (13.6) years and a BMI of 27.0 (4.3) kg/m2]. Plasma apelin-36 was measured using an enzyme immunometric assay method and PTH was measured by ELISA. There was no significant difference in apelin levels between the patients [0.80 (0.6) ng/mL] and the healthy subjects [0.83 (0.23) ng/mL]. There was a positive correlation between apelin and PTH (r = 0.66, p = 0.0001). The patients with PTH >300 pg/mL had significantly higher plasma apelin levels [1.17 (0.7) ng/mL] compared with the patients with PTH <300 pg/mL [0.50 (0.15) ng/mL] (p = 0.003). In conclusion, HD patients with secondary hyperparathyroidism have high plasma apelin levels, which suggest that apelin may protect bone in HD patients by acting as an osteoblastic factor.