EFFECTS OF grape powder SUPPLEMENTATION ON INFLAMMATION IN hemodialysis patients.

Polyphenols and antioxidants anti-inflammatory have been considered pharmacological agents to combat oxidative stress in chronic diseases due the reduction in the formation of free radicals (FR). Hemodialysis (HD) patients have an imbalance between oxidant and antioxidant activity, with increased levels of FR and consequently an increase of lipid peroxidation, thereby raising the risk for cardiovascular disease (CVD). The beneficial health effects of grape juice or red wine for these patients have been attributed to the antioxidant activity of its polyphenols. Then, this study aimed to evaluate the effects of grape powder supplementation on inflammation and glutathione peroxidase levels in hemodialysis (HD) patients. Thirty-two HD patients from CIN, RJ, Brazil were studied and randomly into two groups: placebo group- PG (16 patients, 9 men, 52.7 ± 13.7 yrs) and experimental group EG (16 patients, 9 men, 53.0 ± 9.8 yrs). Each patient received 12g/day of powder grape with grape jelly or only grape jelly (placebo) during 5 weeks. The lipid profile, C-reactive protein (CRP) levels and glutathione peroxidase (GPx) activity were evaluated before and after supplementation (Table). The data suggest that the consumption of grape powder was effective to increase the activity of GPx and decreasing the progression the inflammation. Thus, our results indicate that grape powder plays an important role as an antioxidant agent in HD patients.Placebo GroupExperimental GroupBeforeAfterBeforeAfterCRP (mg/mL)2.6±0.22.8±0.2*2.6±0.22.6±0.2LDL-C86.3±38.894.4±34.380.5±25.082.9±22.1Total cholesterol154.6±44.9163.3±44.8143.9±29.2145.4±28.3GPx (U/g prot)17.5±9.829.1±30.719.7±20.341.0±27.7*⁎p<0.0

Handgrip strength and its dialysis determinants in hemodialysis patients

AbstractObjectiveTo evaluate muscle function (MF) of patients on hemodialysis (HD) and to investigate the dialysis determinants of maximal voluntary handgrip strength (HGS).MethodsForty-three patients on HD (25 men, six diabetics, 54.5 ± 12.2 y of age, 62.2 ± 51.4 mo on dialysis) were studied. HGS was measured three times with a mechanical dynamometer (Jamar) before and after HD sessions on the non-fistula side and the highest value was used for analysis. HGS values lower than the 10th percentile of an age-, gender-, and region-specific reference were considered MF loss. Biochemical and dialysis variables (ultrafiltration, interdialytic body weight gain, urea clearance, urea before and after HD, systolic and diastolic blood pressures before and after HD, and difference in systolic and diastolic blood pressures) were also examined.ResultsThe HGS values before and after HD values were significantly higher in men but were not statistically different before and after the HD sessions (29.8 ± 10.3 and 30.2 ± 9.9 kg for men, 14.1 ± 7.0 and 14.5 ± 6.3 kg for women). MF loss was observed in 24 patients (55.8%), 12 women and 12 men. Dialysis variables were not different between patients with and without MF loss and did not correlate with HGS measured before or after an HD session.ConclusionsPatients using HD presented a high prevalence of MF loss as assessed by HGS, and it was not influenced by dialysis variables. HGS may be used as a reliable nutritional marker in HD, measured before or after HD sessions

Methyl donor nutrients in chronic kidney disease: impact on the epigenetic landscape

Epigenetic alterations, such as those linked to DNA methylation, may potentially provide molecular explanations for complications associated with altered gene expression in illnesses, such as chronic kidney disease (CKD). Although both DNA hypo- and hypermethylation have been observed in the uremic milieu, this remains only a single aspect of the epigenetic landscape and, thus, of any biochemical dysregulation associated with CKD. Nevertheless, the role of uremia-promoting alterations on the epigenetic landscape regulating gene expression is still a novel and scarcely studied field. Although few studies have actually reported alterations of DNA methylation via methyl donor nutrient intake, emerging evidence indicates that nutritional modification of the microbiome can affect one-carbon metabolism and the capacity to methylate the genome in CKD. In this review, we discuss the nutritional modifications that may affect one-carbon metabolism and the possible impact of methyl donor nutrients on the microbiome, CKD, and its phenotype

The uremic toxin indoxyl sulfate exacerbates reactive oxygen species production and inflammation in 3T3-L1 adipose cells

Inflammation and oxidative stress are common features of patients with chronic kidney disease (CKD) and many uremic solutes retained in these patients could be involved in these processes, among which protein-bound solutes such as indoxyl sulfate (IS). White adipose tissue recently gained attention as an important source of inflammation and oxidative stress. To examine the effect of IS on adipocytes, 3T3-L1 adipose cells were incubated with IS to mimic the conditions encountered in uremic patients. Incubation of adipose cells with IS increased reactive oxygen species production generated mainly through activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase since it was prevented by the NADPH oxidase inhibitor apocynin. Exposure to IS furthermore exacerbated the secretion of tumor necrosis factor- and interleukin-6 by adipose cells. This inflammatory response was prevented by NADPH oxidase inhibition pinpointing the pivotal role of intracellular oxidative stress. IS induces adipocyte perturbation and promotes inflammatory state mainly through induction of oxidative stress. IS, a uremic toxin, accumulates in CKD patients could, therefore, be an important mediator of adipocyte dysfunction in these patients

Associação entre níveis de ferritina e peroxidação lipídica em pacientes em hemodiálise

Resumo Introdução: A suplementação de ferro é uma das importantes recomendações em pacientes com doença renal crônica (DRC), contudo, uma sobrecarga desse mineral pode contribuir para o estresse oxidativo, condição essa bastante relacionada com o risco cardiovascular nesses pacientes. Objetivo: O objetivo desse trabalho foi investigar se os níveis de ferritina estão associados ao estresse oxidativo avaliado pelo malondialdeído (MDA) em pacientes em hemodiálise (HD). Métodos: Vinte pacientes em tratamento de HD (55,0 ± 15,2 anos, tempo de diálise de 76,5 ± 46,3 meses, IMC 23,6 ± 3,0 kg/m2) foram comparados com 11 indivíduos saudáveis (50,9 ± 8,0 anos, IMC 23,8 ± 1,9 kg/m2). O nível de MDA foi medido pela reação com o ácido tiobarbitúrico e os dados bioquímicos de rotina foram obtidos por meio do prontuário médico. Resultados: Os pacientes em HD apresentaram elevados níveis de MDA (13,2 ± 5,3 nmol/mL) quando comparados aos indivíduos saudáveis (5,1 ± 2,7 nmol/mL; p < 0,01). Doze pacientes (60%) apresentaram valores de ferritina superiores a 500 ng/mL e houve correlação positiva entre ferritina e MDA nos pacientes HD (r = 0,66; p = 0,005; n = 17). Conclusão: O excesso dos estoques de ferro em pacientes em HD resulta em um aumento da peroxidação lipídica e, consequentemente, contribui para um maior estresse oxidativo nesses pacientes

ASSOCIATION BETWEEN HANDGRIP STRENGTH AND INFLAMMATION IN HEMODIALYSIS PATIENTS

The inflammation is a common feature in HD patients and may contribute to muscle wasting. Handgrip strength (HGS) has been recognized as a useful tool in assessing muscle function in hemodialysis (HD) patients. The aim of this study was to evaluate the association between inflammation and muscle function in HD patients. Twenty-three HD patients (19 men, 54.3±12.4 years of age, BMI, 24.5±4.6kg/m2) were studied. HGS was measured 3x with a mechanical dynamometer after the HD sessions. HGS values less than the 10th percentile of an age-, gender- and regional specific reference were considered as muscle function loss. Tumoral necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were determined by a multiplex assay kit through the device Luminex method. C-reactive protein (CRP) was measured with the immunoturbidimetric method. HGS values were significantly greater in males (28.8±9.7 kg) than females (13.9±6.5kg) (p <0.0001) and, 57.6% of the HD patients presented muscle function loss. TNF-α, IL-6 and CRP levels were 5.6±1.7pg/mL, 3.5 (1.75) pg/mL and 0.17 (0.50) mg/dL, respectively. According to the CRP levels, 42.4% of the HD patients presented inflammation (CRP > 0.3mg/dL). CRP and IL-6 were not correlated with HGS, but TNF-α were inversely correlated with HGS (r =-0.42; p = 0.01). These data suggest that inflammation can play an important role on muscle function in HD patients.fx

Determination of the binding properties of the uremic toxin phenylacetic acid to human serum albumin

Uremic toxins are compounds normally excreted in urine that accumulate in patients with chronic kidney disease as a result of decreased renal clearance. Phenylacetic acid (PAA) has been identified as a new protein bound uremic toxin. The purpose of this study was to investigate in vitro the interaction between PAA and human serum albumin (HSA) at physiological and pathological concentrations. We used ultrafiltration to show that there is a single high-affinity binding site for PAA on HSA, with a binding constant on the order of 3.4 x 10(4) M-1 and a maximal stoichiometry of 1.61 mol per mole. The PAA, at the concentration reported in end-stage renal patients, was 26% bound to albumin. Fluorescent probe competition experiments demonstrated that PAA did not bind to Sudlow's site I (in subdomain IIA) and only weakly bind to Sudlow's site II (in subdomain IIIA). The PAA showed no competition with other protein-bound uremic toxins such as p-cresyl-sulfate or indoxyl sulfate for binding to serum albumin. Our results provide evidence that human serum albumin can act as carrier protein for phenylacetic acid. (C) 2016 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM)

Systemic inflammation and oxidative stress in hemodialysis patients are associated with down-regulation of Nrf2.

BackgroundOxidative stress and inflammation are common features and the main mediators of progression of chronic kidney disease (CKD) and its cardiovascular complications. Under normal conditions, oxidative stress activates the transcription factor, nuclear factor E2-related factor 2 (Nrf2), which is the master regulator of genes encoding antioxidant and detoxifying enzymes and related proteins. The available data on expression of Nrf2 and its key target gene products in CKD patients is limited. We therefore investigated this topic in a group of CKD patients on hemodialysis.MethodsTwenty adult hemodialysis (HD) patients (aged 54.9 ± 15.2 years) and 11 healthy individuals (aged 50.9 ± 8.0 years) were enrolled. Peripheral blood mononuclear cells (PBMC) were isolated and processed for expression of nuclear factor-κB (NF-κB), Nrf2, heme oxygenase-1 and NADPH: quinoneoxidoreductase 1 (NQO1) by quantitative real-time polymerase chain reaction and western blot analysis. Plasma malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) levels were measured.ResultsPeripheral blood mononuclear cells from HD patients had significantly lower NQO1 and Nrf2 mRNA expressions (0.58 ± 0.35 vs. 1.13 ± 0.64, p = 0.005), and significantly higher NF-κB expression (2.18 ± 0.8 vs. 1.04 ± 0.22, p = 0.0001) compared to the healthy individuals. The NF-κB expression was inversely correlated with Nrf2 levels (r = -0.54, p &lt; 0.01) in CKD patients. Plasma MDA and TNF-α levels were significantly higher in CKD patients than in the healthy individuals.ConclusionsUp-regulation of NFκB in the CKD patients' PBMC is coupled to down-regulation of Nrf2 and NQO1 expression. These observations are consistent with recent findings in CKD animals and point to the contribution of the impaired Nrf2 system in the pathogenesis of oxidative stress and inflammation in hemodialysis patients

Apelin in hemodialysis patients: is there relationship with oxidative and inflammation markers?

Inflammation and oxidative stress are importante features associated with pathogenesis of cardiovascular disease in hemodialysis (HD) patients. Apelin is a bioactive peptide involved in a variety of physiological functions that has been associated with inflammation, however; little is known about apelin in chronic kidney disease (CKD). Thus, the purpose of this study was to analyse apelin plasma levels in HD patients and verify if there is any relationship with inflammation and oxidative markers. Twenty-four HD patients (53.6±14.4 years of age, 14 men and body mass index (BMI) of 25.0±4.2 kg/m2) were studied and compared to 15 healthy subjects (51.3±13.5 years of age, 7 men and BMI of 26.3±3.7 kg/m2). Plasma apelin-12 and -36 were measured using the enzyme immunometric assay (EIA) method. Plasma electronegative low density lipoprotein (LDL-) levels were measured using ELISA method. The levels of tumor-necrosis factor-α (TNF-α), interleukin-6, leptin and plasminogen activator inhibitor-1 were measured by a multiplex assay kit and C-reactive protein (CRP) by immunoturbidimetry. 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 than in healthy subjects, 0.24± 0.13ng/mL. Inflammation (TNF-α and CRP) and oxidative markers levels (LDL-) were higher in HD patients (5.4±1.3 pg/mL, 0.15 (0.33) mg/dL and 0.19±0.13U/L, respectively); however, there was not correlation among apelin-12 or -36 and inflammatory or oxidative markers. In conclusion, plasma apelin seems to be not associated with inflammatory and oxidative status in HD patients