Effects of Probiotic Supplementation on Trimethylamine-N-Oxide Plasma Levels in Hemodialysis Patients: a Pilot Study.

Components present in the diet, L-carnitine, choline, and betaine are metabolized by gut microbiota to produce metabolites such as trimethylamine-N-oxide (TMAO) that appear to promote cardiovascular disease in chronic kidney disease (CKD) patients. The objective of this pilot study was to evaluate the effects of probiotic supplementation for 3 months on plasma TMAO levels in CKD patients on hemodialysis (HD). A randomized, double-blind trial was performed in 21 patients [54.8 ± 10.4 years, nine men, BMI 26.1 ± 4.8 kg/m2, dialysis vintage 68.5 (34.2-120.7) months]. Ten patients were randomly allocated to the placebo group and 11 to the probiotic group [three capsules, totaling 9 × 1013 colony-forming units per day of Streptococcus thermophilus (KB19), Lactobacillus acidophilus (KB27), and Bifidobacteria longum (KB31). Plasma TMAO, choline, and betaine levels were measured by LC-MS/MS at baseline and after 3 months. While TMAO did not change after probiotic supplementation, there was a significant increase in betaine plasma levels. In contrast, the placebo group showed a significant decrease in plasma choline levels. Short-term probiotic supplementation does not appear to influence plasma TMAO levels in HD patients. Long-term studies are needed to determine whether probiotics may affect TMAO production in CKD patients.

Does resistance exercise performed during dialysis modulate Nrf2 and NF-κB in patients with chronic kidney disease?

Studies have shown that nuclear factor erythroid 2-related factor 2 (Nrf2) can be modulated by physical exercise. However, the impact of resistance exercise has never been investigated in patients with chronic kidney disease (CKD). The aim of this study was to evaluate the effects of resistance exercise programs on the expression of transcription factors Nrf2 and nuclear factor κB (NF-κB) in CKD patients on hemodialysis (HD). Patients on an HD program were randomly assigned to an exercise group of 25 patients (54.5% women, aged 45.7±15.2years and time on dialysis=71.2±45.5months) or a control group of 19 patients who had no exercise intervention (61.5% women, aged 42.5±13.5years and time on dialysis=70.1±49.9months). A strength exercise program was performed 3 times a week during the HD sessions. Peripheral blood mononuclear cells were isolated and processed for the expression of Nrf2 and NF-κB by quantitative real-time polymerase chain reaction 3months before and after the exercise program. Using an enzyme-linked immunosorbent assay, the activity of glutathione peroxidase (GPx) as well as the products of high-sensitivity C-reactive protein and nitric oxide (NO) were assessed. Nrf2 expression (ranging from 0.86±0.4 to 1.76±0.8) and GPx activity were significantly increased after exercise intervention. In the exercise group, no difference in the levels of NO was observed; however, there was a significant reduction in the control group. In conclusion, these data suggest that resistance exercises seem to be capable of inducing Nrf2 activation in CKD patients on HD.

A follow-up study of the chronic kidney disease patients treated with Brazil nut: focus on inflammation and oxidative stress.

Brazil nut is the richest known food source of selenium. The supplementation with Brazil nut during 3 months was effective in reducing oxidative stress and inflammation in hemodialysis (HD) patients. However, there are no available data on the antioxidant effect after that supplementation. The objective of this work was to determine if the beneficial effects of one Brazil nut supplementation per day during 3 months for the HD patients could be sustained after 12 months. Twenty-nine HD patients (58.6 % men, 51.0 ± 3.3 years) from RenalCor Clinic, Rio de Janeiro, Brazil, were followed up 12 months after the supplementation study had finished. The plasma levels of antioxidant substances as selenium, glutathione peroxidase (GPx), 8-isoprostane, 8-hydroxy-2-deoxyguanosine (8-OHdG) and cytokines (tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6)) were determined before, after 3 months of supplementation and after 12 months. After 3-months supplementation, cytokines, 8-OHdG and 8-isoprostane plasma levels have decreased and the activity of GPx and selenium plasma levels have increased significantly. Additionally, after 12 months, the values of 8-isoprostane, 8-OHdG and cytokines increased and the activity of GPx and selenium plasma levels decreased significantly. The levels of oxidative stress and inflammation biomarkers after 12 months increased compared to the basal levels. Consequently, it is necessary to motivate patients to adopt different dietary intake patterns.

The newly identified anorexigenic adipokine nesfatin-1 in hemodialysis patients: Are there associations with food intake, body composition and inflammation?

Nesfatin-1 is a recently identified anorexigenic peptide that has been implicated in appetite regulation, weight loss and/or malnutrition. Anorexia and malnutrition are common features of chronic kidney disease (CKD) that predispose patients to worse outcomes. However, the reasons for the occurrence of anorexia in CKD patients are not fully elucidated. The aim of this study was to investigate the association between nesfatin-1 and protein intake and body composition in patients undergoing hemodialysis (HD). Twenty five HD patients from a private Clinic in Rio de Janeiro, Brazil were studied and compared with 15 healthy subjects that were matched for body mass index (BMI), % body fat mass (by anthropometrics) and age. Appetite was measured using a specific questionnaire, and food intake was evaluated based on 3-day food records. Nesfatin-1 levels were measured by ELISA and leptin, TNF-α and IL-6 levels were determined by a multiplex assay kit. Serum nesfatin-1 levels did not differ between HD patients (0.16±0.07ng/mL) and healthy subjects (0.17±0.10ng/mL). Nesfatin-1 levels showed significant negative correlations with protein intake (r=-0.42; p=0.03), but did not associate with inflammatory markers or appetite scores. Combining patients and controls, we observed positive correlations with BMI (r=0.33; p=0.03), % body fat (r=0.35; p=0.03), leptin (r=0.45; p=0.006) and the triceps skinfold thickness (r=0.36; p=0.02). In multivariate analysis % body fat was the main determinant of nesfatin-1 variance. In conclusion, nesfatin-1 levels did not differ between HD patients and healthy subjects and negatively correlated with protein intake. This pathway is likely not dysregulated in uremia.

Relationship between total ghrelin and inflammation in hemodialysis patients.

In hemodialysis (HD) patients studies have shown that plasma ghrelin is increased and it has been speculated that ghrelin levels might be related to systemic inflammation. The present study attempted to correlate the serum levels of total ghrelin with serum TNF-α and IL-6, and with nutritional status and body composition in HD patients. Forty-seven HD patients from a single dialysis unit (18 women, mean age 55.3±12.2 yr; BMI 24.4±4.2kg/m(2); % body fat 29.4±7.4%) were studied and compared to 21 healthy subjects (12 women, 50.7±15.7 yr and BMI 25.6±4.0kg/m(2); % body fat 30.0±5.7%). Biochemical data, serum total ghrelin, TNF-α and IL-6 levels were measured. The body composition was evaluated by dual energy X-ray absortiometry (DEXA) and energy and protein intake were evaluated. Patients showed elevated plasma ghrelin levels when compared to healthy subjects (1.14±1.0ng/mL vs 0.58±0.4; p<0.001). There was a positive correlation between ghrelin levels and TNF-α (r=0.25; p<0.04), IL-6 (r=0.42; p<0.02), and a negative correlation between TNF-α and protein intake (r=-0.28; p<0.03), and energy intake (r=-0.34; p<0.01). No correlation was observed with any aspect of body composition. Plasma ghrelin levels are elevated in HD patients and associated with the state of systemic inflammation. We suggest that the inflammatory state may affect ghrelin bioactivity and metabolism in hemodialysis patients.

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.