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Uremic toxins such as indoxyl sulfate (IS), p-cresyl sulfate (pCS), and indole-3-acetic acid (IAA) produced by the gut microbiota are recognized as risk factors for many comorbidities, including cardiovascular diseases. Patients with chronic kidney disease (CKD) have an accumulation of these toxins, and nutritional strategies have been proposed to mitigate gut dysbiosis and, consequently, reduce these toxins. This study aimed to evaluate the effects of resveratrol supplementation on the plasma levels of IS, pCS, and IAA in nondialyzed patients with CKD.In this placebo-controlled crossover study, twenty nondialyzed patients were randomly divided into two groups: they received either one capsule/day containing 500 mg of trans-resveratrol (63 ± 7.5 years, glomerular filtration rate [GFR]: 34 ± 14 mL/min, body mass index: 26.8 ± 5.6 kg/mAs expected, the uremic toxin levels were negatively correlated with the GFR, but no effect of trans-resveratrol supplementation was found on levels of IS, IAA, and pCS. There was a positive correlation between IS and nuclear factor erythroid 2-related factor 2 (r = 0.24, P = .03) and also between IS and C-reactive protein (r = 0.21, P = .05).Supplementation with trans-resveratrol did not reduce the plasma levels of IS, pCS, and IAA in nondialyzed patients with CKD. The interactions among uremic toxins and anti-inflammatory and proinflammatory pathways deserve more studies.

Peroxisome proliferator-activated receptor-gamma (PPAR-γ) plays a central role in health and is an essential cardioprotective factor because of its effect on lipid and glucose metabolism, inflammation, and oxidative stress. We hypothesized that nutritional strategies positively regulate PPAR-γ expression in patients with noncommunicable diseases (NCDs). A systematic search was conducted using PubMed, Scientific Electronic Library Online (SciELO), and LILACS databases from May 2020 to January 2021. Eligibility criteria included placebo-controlled randomized clinical trials in adults with chronic diseases involving nutritional strategies, which performed PPAR-γ analysis (majority on mononuclear cells) before and after the intervention. The exclusion criteria included studies published more than 10 years ago, studies not published in English or Spanish, theses, reviews, and other study designs. The review was developed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Methodological quality was assessed based on 7 criteria obtained from the Cochrane Handbook. A total of 7 studies were included that reported the effects of different nutritional strategies (such as anthocyanins, fish oil, Berberis vulgaris juice, ketogenic diet, flaxseed oil, olive oil) on 346 patients with NCDs (such as type 2 diabetes, hypertension, obesity, and cancer) between 18 and 85 years of age. These results suggest that anthocyanins, flaxseed oil, and olive oil may function as putative PPAR-γ agonists.

Summary Background & Aims Patients with Chronic Kidney Disease (CKD) have an imbalance in the gut microbiota that can lead to increase levels of lipopolysaccharides (LPS) and uremic toxins such as indoxyl sulfate (IS), p-cresyl sulfate (p-CS), and indole-3 acetic acid (IAA). Among the therapeutic options for modulating gut microbiota are the bioactive compounds such as polyphenols present in cranberry, fruit with potential antioxidant and anti-inflammatory effects. This clinical trial focuses on evaluating the effects of supplementation with a dry extract of cranberry on plasma levels of LPS and uremic toxins in non-dialysis CKD patients. Methods It was a randomized, double-blind, placebo-controlled study. Patients were randomized into two groups: the cranberry group received 500 mg of dry cranberry extract (2 times daily), and the placebo group received 500 mg of corn starch (2 times daily) for two months. LPS plasma levels were evaluated by enzyme-linked immunosorbent assay (ELISA) and uremic toxins (IS, p-CS, and IAA) by high-performance liquid chromatography-fluorescence detection. Anthropometric measurements and food intake using the 24-hour food recall technique were also evaluated before and after the intervention. Results Twenty-five participants completed two months of supplementation: 12 patients in the cranberry group (8 women, 56.7 ± 7.5 years, estimated glomerular filtration rate (eGFR) of 39.2 ± 21.9 mL/min); 13 patients in the placebo group (9 women, 58.8 ± 5.1 years, eGFR of 39.7 ±12.9 mL/min). As expected, there was a negative association between glomerular filtration rate and p-CS and IS plasma levels at the baseline. No change was observed in the uremic toxins and LPS levels. Conclusion Cranberry dry extract supplementation for two months did not reduce the LPS and uremic toxins plasma levels produced by the gut microbiota in non-dialysis CKD patients.

The increasing consumption of ultra-processed food (UPF) and the global chain of food production have a negative impact on human health and planetary health. These foods have been replacing the consumption of nonprocessed healthy foods. This shift has not only worsened human health by increasing the risk of the development of noncommunicable diseases, but also resulted in environmental perturbations. This review aims to bring awareness of the problems caused by the industrialized food production chain, addressing the negative effects it has on the environment and human health, with special reference to chronic kidney disease (CKD). We discuss possible solutions focusing on the benefits of adopting plant-based diets with low UPF content to promote a sustainable and healthy food production and diet for patients with CKD. For a sustainable future we need to "connect the dots" of planetary health, food production, and nutrition in the context of CKD.

Objective The aim of this study was to evaluate the association between zinc plasma levels and sensory perception in patients with chronic kidney disease (CKD). Methods A cross-sectional study with 21 nondialysis CKD patients (11 men, 51.1 ± 7.1 years, body mass index 27.9 ± 7.1 kg/m2, estimated glomerular filtration rate 32.7 ± 19.9 mL/min) and 22 non-CKD volunteers (10 men, 49.8 ± 8.3 years, body mass index 28.5 ± 5.4 kg/m2) was conducted. Blood samples were collected to obtain plasma for zinc analysis. Anthropometric and biochemical parameters, as well as food intake and salivary flow rate, were also evaluated. Taste sensory perception for sweet, acidic, bitter, and salty flavors was determined by the “three-drop method,” with 4 concentrations of the 4 basic tastes. Results As expected, zinc plasma levels were significantly lower in CKD patients (70.1 ± 19.2ug/dL) when compared with the control group participants (123.2 ± 24.6 μg dL) (P ˂ .0001). The bitter taste perception was lower in the CKD group (p˂0.0001). Our findings showed that sensitivity to sour (P = .047), salty (P = .03), and bitter tastes was significantly lower in participants with lower zinc plasma levels. Also, bitter taste sensitivity was lower in participants with less zinc intake (P = .038). When grouping control subjects and CKD patients, significant correlations were observed between zinc plasma levels and the number of correct answers for bitter taste (r = 0.49, P = .001), number of correct answers for salty taste (r = 0.30, P = .048), and total score of correct answers (r = 0.30, P = .044). Conclusions Reduced zinc plasma levels in nondialysis CKD patients may be associated with lower perception of bitter, sour, and salty tastes and strategies to restore these levels are crucial due many factors, including food preferences and intake.

Chronic kidney disease patients on hemodialysis commonly have a worse quality of life (QoL) due to complications of the disease and dialysis procedure. Physical exercise has emerged as a strategy to improve this scenario. The objective of this study was to evaluate the effect of an intradialytic aerobic exercise program on QoL and aerobic fitness in hemodialysis patients.These are a secondary analysis of clinical trial data previously published in which hemodialysis patients were randomized into "bike group" (using an adapted exercise bicycle) or "control group" (usual care). The exercise sessions lasted 45 min (5 min of warm-up, 35 min of moderate-intensity and 5 min of cool-down) three times/week for three months. The QoL domains were assessed using the SF-36 QoL questionnaire. Aerobic fitness was evaluated using the 6-min walk test (6MWT). Circulating cytokines, biochemical parameters and Kt/V were also assessed.Nine patients completed three months of exercise (5 men, 44 ± 11 years), and nine were in the control group (6 men, 44 ± 14 years). In the bike group, there was a trend to improve the physical role domain (p = 0.06) regarding QoL, an improvement in the 6MWT (p = 0.02), and in the Kt/V (p = 0.03) after three months. There was a positive correlation between the general health domain and Kt/V (r = 0.691; p = 0.003) and an inverse correlation between the physical functioning domain and plasma TNF-α levels (r = -0.514; p = 0.04).12 weeks of intradialytic aerobic exercise was enough to benefit hemodialysis patients' quality of life, aerobic fitness, and quality of dialysis.gov id: NCT04375553.

Archaea comprise a unique domain of organisms with distinct biochemical and genetic differences from bacteria. Methane-forming archaea, methanogens, constitute the predominant group of archaea in the human gut microbiota, with Methanobrevibacter smithii being the most prevalent. However, the effect of methanogenic archaea and their methane production on chronic disease remains controversial. As perturbation of the microbiota is a feature of chronic conditions, such as cardiovascular disease, neurodegenerative diseases and chronic kidney disease, assessing the influence of archaea could provide a new clue to mitigating adverse effects associated with dysbiosis. In this review, we will discuss the putative role of archaea in the gut microbiota in humans and the possible link to chronic diseases.

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.

BTB and CNC homology 1 (Bach1) is a protein that forms nuclear heterodimers with the small musculoaponeurotic fibrosarcoma (sMaf). These bind to genomic DNA, promoting the inhibition of the synthesis of a range of antioxidant enzymes. This heterodimer antagonises the actions of nuclear factor erythroid 2-related factor-2 (Nrf2), a master regulator of cytoprotective responses in the cells. Studies have shown that Nrf2 expression is downregulated and Bach1 expression upregulated in many chronic diseases; hence Nrf2 activators and Bach1 inhibitors need to be investigated for their potential to mitigate inflammation and improve antioxidant responses in the chronic burden of lifestyle diseases, including chronic kidney disease. Thus, this review will discuss the status of Bach1 in such diseases and the use of possible inhibitors as a promising therapeutic approach.

International audience; No abstract available

Probiotics may mitigate the generation of uremic toxins and inflammatory biomarkers. The aim of this study was to evaluate the effects of probiotics on uremic toxins and inflammatory biomarkers in CKD. In this randomized, double-blind, placebo-controlled trial, 30 patients (63.8 ± 7.5 years, 14 men, mean BMI of 27.2 ± 3.8 kg/m2) were assigned to receive one of two treatments: probiotics (n = 15; Streptococcus thermophilus, Lactobacillus acidophilus and Bifidobacteria longum-90 billion CFU per day) or placebo (n = 15) daily for three months. Plasma uremic toxins were measured using reversed-phase liquid-chromatography (RP-HPLC); choline, betaine and trimethylamine-N-oxide (TMAO) were measured using liquid chromatography–mass spectrometry (LC-MS/MS); and inflammatory biomarkers were measured using ELISA. Uremic toxins were not influenced by the probiotics; however, IL-6 levels increased significantly from 15.6 (14.8–20.8) pg/mL to 23.0 (17.6–29.6) pg/mL, p = 0.01. There was a positive correlation between the levels of p-cresyl sulfate and urea (r = 0.55; p = 0.02) and between TMAO and CRP (r = 0.46; p = 0.05) at baseline. These data suggest that probiotic supplementation did not result in expected benefits for non-dialysis CKD patients.

Objectives To evaluate the effects of low-protein diet (LPD) on uremic toxins and the gut microbiota profile in nondialysis chronic kidney disease (CKD) patients. Design and Methods Longitudinal study with 30 nondialysis CKD patients (stage 3-4) undergoing LPD for 6 months. Adherence to the diet was evaluated based on the calculation of protein equivalent of nitrogen appearance from the 24-hour urine analysis. Good adherence to LPD was considered when protein intake was from 90% to 110% of the prescribed amount (0.6 g/kg/day). Food intake was analyzed by the 24-hour recall method. The anthropometric, biochemical and lipid profile parameters were measured according to standard methods. Uremic toxin serum levels (indoxyl sulfate, p-cresyl sulfate, indole-3-acetic acid) were obtained by reversed-phase high-performance liquid chromatography (RP-HPLC). Fecal samples were collected to evaluate the gut microbiota profile through polymerase chain reaction and denaturing gradient gel electrophoresis. Statistical analysis was performed by the SPSS 23.0 program software. Results Patients who adhered to the diet (n = 14) (0.7 ± 0.2 g/kg/day) presented an improvement in renal function (nonsignificant) and reduction in total and low-density lipoprotein cholesterol (183.9 ± 48.5-155.7 ± 37.2 mg/dL, P = .01; 99.4 ± 41.3-76.4 ± 33.2 mg/dL, P = .01, respectively). After 6 months of nutricional intervention, p-cresyl sulfate serum levels were reduced significantly in patients who adhered to the LPD (19.3 [9.6-24.7] to 15.5 [9.8-24.1] mg/L, P = .03), and in contrast, the levels were increased in patients who did not adhere (13.9 [8.0-24.8] to 24.3 [8.1-39.2] mg/L, P = .004). In addition, using the denaturing gradient gel electrophoresis technique, it was observed change in the intestinal microbiota profile after LPD intervention in both groups, and the number of bands was positively associated with protein intake (r = 0.44, P = .04). Conclusion LPD seems be a good strategy to reduce the uremic toxins production by the gut microbiota in nondialysis CKD patients.

Red meat is an important dietary source of high biological value protein and micronutrients such as vitamins, iron, and zinc that exert many beneficial functions. However, high consumption of animal protein sources, especially red meat, results in an increased intake of saturated fat, cholesterol, iron, and salt, as well as an excessive acid load. Red meat intake may lead to an elevated production of uremic toxins by the gut microbiota, such as trimethylamine n-oxide (TMAO), indoxyl sulfate, and p-cresyl sulfate. These uremic toxins are associated with increased risk for cardiovascular (CV) mortality. Limiting the intake of red meat in patients with chronic kidney disease (CKD) thus may be a good strategy to reduce CV risk, and may slow the progression of kidney disease. In the present review, we discuss the role of red meat in the diet of patients with CKD. Additionally, we report on a pilot study that focused on the effect of a low-protein diet on TMAO plasma levels in nondialysis CKD patients.

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.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor with a high sensitivity to oxidative stress, which regulates the expression of detoxifying enzymes, besides that, can also control antioxidant and anti-inflammatory cellular responses. Therefore, the modulation of this transcription factor can be a new therapeutic approach to reduce complications in chronic kidney disease (CKD) patients, like oxidative stress and inflammation, which leads to increased risk of developing cardiovascular disease, the major cause of death in these patients. Recent studies have shown that nutritional components and physical exercises can regulate the activation of Nrf2; however, very few studies were performed in CKD patients. This review provides an overview about some of the nonpharmacologic strategies that may promote the activation of Nrf2, which may have impact on the human health, particularly in CKD, by preventing oxidative stress and maintaining cellular redox homeostasis.

Summary Objective The aim of this study was evaluate the effects of resistance exercise on bone markers in HD patients. Material and methods Twenty-six patients undergoing hemodialysis were assigned to either an exercise group (EG – n = 14) or a control group (CG – n = 12). The EG performed approximately six months of intradialytic resistance exercise program (using elastic bands and leggings with both lower limbs) monitored thrice weekly (72 sessions), while the CG received standard care. Plasma bone markers (osteoprotegerin – OPG, osteocalcin – OC, Osteopontin – OPN and intact parathyroid hormone-iPTH) were measured by Luminex. Results OPG levels increased significantly after resistance training in EG (from 6.8 ± 1.8 to 7.8 ± 1.8 ng/L, P = 0.02), whereas OC, OPN and iPTH did not change. Conclusion In summary, resistance exercise may have contributed to the increase in OPG plasma levels and probably to the prevention of bone loss among HD patients who participated in the exercise program.

Studies have revealed complex interactions between bone and fat, however there are few studies about this crosstalk in patients with chronic kidney disease. This study investigated possible relationship between bone mineral density (BMD) and body composition in patients who underwent hemodialysis. Twenty patients were enrolled in a cross-sectional study (47.0 [42.3-56.8] years, body mass index 26.0 ± 4.2 kg/m, dialysis vintage of 48.5 [26.7-95.7] months). Body composition and BMD were assessed by dual-energy X-ray absorptiometry. Leptin and parathormone levels were analyzed using Multiplex kits (RD System Inc). Low bone mass in the femoral neck was reported in 54.8% of patients. Total BMD and total T-score were positively correlated with lean mass (r = 0.46, P = 0.04; r = 0.47, P = 0.04, respectively), but not with leptin or body fat mass. In conclusion, lean body mass is probably important to maintain bone health in male patients who underwent hemodialysis.

Patients with chronic kidney disease (CKD) have various metabolic disorders caused by a chronic state of oxidative stress and inflammation, and recently, nuclear factor-erythroid 2-related factor 2 (Nrf2) has emerged as a factor that plays a significant role in cellular protection against oxidative stress and inflammation. This transcription factor when activated can regulate antioxidant and anti-inflammatory cellular responses leading to the expression of detoxifying enzymes. Studies have shown that Nrf2 expression can be modulated by several factors, such as bioactive compounds and physical exercise. In fact, exercise in CKD patients can bring many benefits; however, there are no studies correlating physical activity and Nrf2 expression in CKD patients. This review aims to discuss whether there is any evidence to justify a recommendation of physical exercise in CKD patients as a non-pharmacological option to activate the Nrf2 pathway.

Inflammation and oxidative stress are two major components involved in the atherogenic process generated by the innate immune response to lipoprotein peroxidation, which is accelerated in patients with chronic kidney disease (CKD). Whereas the redox-sensitive transcription factor nuclear factor-κB (NF-κB) plays an important role in the coordinated expression of inflammatory genes, the nuclear factor E2-related factor 2 (Nrf2) is the transcription factor that is responsible for both constitutive and inducible expression of antioxidant response element (ARE)-regulated genes. Thus, Nrf2 can regulate antioxidant and anti-inflammatory cellular responses of this system, playing an important protective role on the development of the uremic phenotype. This review describes the Nrf2 system and its possible role in CKD patients.

Objective: To evaluate the body composition and inflammatory status in patients on hemodialysis (HD) according to the cutoff of 23 kg/m 2 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-a, 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/m 2 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/m 2 , but the mean values did not indicate energy wasting. Patients with a BMI higher than 23 kg/m 2 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-a, and interleukin-6 predict cardiovascular mortality. Conclusion: Patients on HD with a BMI lower than 23 kg/m 2 did not present signs of energy wasting, whereas those with a BMI higher than 23 kg/m 2 had more inflammation, probably because of a greater adiposity. Thus, the BMI value of 23 kg/m 2 does not seem to be a reliable marker of protein–energy wasting in patients on HD.

Recent evidences suggested a possible relationship between zinc deficiency and leptin levels in pathogenesis of anorexia in chronic kidney disease. The present study addressed the relationship between zinc and leptin in hemodialysis (HD) patients. Methods Fifty HD patients (54.3 ± 12.7 years old, 62% men) were studied and compared to 21 healthy volunteers (50.7 ± 15.7 years old, 43% men). Biochemical data, serum zinc, plasma leptin, IL-6, TNF-α and C-Reactive Protein levels were determined. Anthropometric parameters, food intake and appetite score were also assessed. Results The leptin levels were higher in HD patients (16.1 μg/mL (0.21–118.25) vs 6.0 μg/mL (0.50–23.10)) in healthy volunteers (p = 0.04), whereas serum zinc levels were lower (54.5 ± 16.3 μg/dL) compared to healthy volunteers (78.4 ± 9.4 μg/dL) (p = 0.0001). The plasma leptin was correlated negatively with plasma zinc (r = −0.33; p = 0.007), energy (r = −0.38; p = 0.002) and protein intake (r = −0.34; p = 0.006) and, positively correlated with BMI (r = 0.54; p = 0.0001), % body fat (r = 0.70; p = 0.0001) and conicity index (r = 0.46; p = 0.001). Plasma zinc was associated with hemoglobin (r = 0.30; p = 0.04) and negatively associated with TNF-α (r = −0.37; p = 0.002) and C-Reactive Protein (r = −0.37; p = 0.004). There was no correlation among Zn, leptin and appetite score in these patients. Conclusion This study showed that low plasma zinc levels are negatively associated with high leptin levels in HD patients.

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.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.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.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).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.

The incidence of malnutrition disorders in chronic kidney disease (CKD) appears unchanged over time, whereas patient-care and dialysis techniques continue to progress. Despite some evidence for cost-effective treatments, there are numerous caveats to applying these research findings on a daily care basis. There is a sustained generation of data confirming metabolic improvement when patients control their protein intake, even at early stages of CKD. A recent protein-energy wasting nomenclature allows a simpler approach to the diagnosis and causes of malnutrition. During maintenance dialysis, optimal protein and energy intakes have been recently challenged, and there is no longer an indication to control hyperphosphatemia through diet restriction. Recent measurements of energy expenditure in dialysis patients confirm very low physical activity, which affects energy requirements. Finally, inflammation, a common state during CKD, acts on both nutrient intake and catabolism, but is not a contraindication to a nutritional intervention, as patients do respond and improve their survival as well as do noninflamed 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; p0.001). There was a positive correlation between ghrelin levels and TNF-α (r=0.25; p0.04), IL-6 (r=0.42; p0.02), and a negative correlation between TNF-α and protein intake (r=-0.28; p0.03), and energy intake (r=-0.34; p0.01). 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.

Both leptin and ghrelin (in the forms of acyl ghrelin and des-acyl ghrelin) are involved in food intake, and appear to be dysregulated in chronic kidney disease. This study describes plasma leptin, acyl, and des-acyl ghrelin concentrations in relation to protein intake and body mass index (BMI) in hemodialysis (HD) patients.This was a cross-sectional study.This study was conducted during the baseline phase of the French multicenter Influence of a High-Flux Dialyzer on Long-Term Leptin Levels Study.We studied 125 HD patients (aged 72.5+/-11.7 years; 59% males).Blood samples were collected during fasting, and before a regular HD session. Plasma ghrelin and leptin were evaluated. The protein equivalents of total nitrogen appearance and BMI were calculated.Patients demonstrated elevated serum leptin (48.0+/-49.0 ng/mL) and des-acyl ghrelin (646.6+/-489.5 pg/mL) levels, and low acyl ghrelin levels (29.8+/-58.5 pg/mL), according to normal values. Acyl ghrelin was negatively correlated with C-reactive protein (r=-0.34, P.001). The des-acyl to acyl ghrelin ratio was negatively correlated with protein intake, as estimated by normalized Protein Nitrogen Appearance (r=-0.22, P=.01). Serum leptin exhibited its well-described positive correlation with BMI and waist circumference, but the other hormones did not.This study reports high des-acyl ghrelin and leptin levels and low acyl ghrelin levels in HD patients, a finding potentially associated with inflammation and food intake.

The stomach may play an important role in central feeding regulation because it produces two peptides, ghrelin and the recently identified obestatin. These peptide hormones exert opposite actions on weight regulation. Whereas ghrelin is orexigenic, obestatin seems to be anorexigenic. Studies on feeding regulation are of particular importance for patients with chronic kidney disease (CKD), because anorexia and weight loss are associated with wasting and increased morbidity and mortality. This review discusses recent information about ghrelin and obestatin and their potential role in CKD. In addition, it seems important to consider not only single values but also their ratios, because both compounds could be affected disharmoniously by CKD.

The accurate estimation of total daily energy expenditure (TEE) in chronic kidney patients is essential to allow the provision of nutritional requirements; however, it remains a challenge to collect actual physical activity and resting energy expenditure in maintenance dialysis patients. The direct measurement of TEE by direct calorimetry or doubly labeled water cannot be used easily so that, in clinical practice, TEE is usually estimated from resting energy expenditure and physical activity. Prediction equations may also be used to estimate resting energy expenditure; however, their use has been poorly documented in dialysis patients. Recently, a new system called SenseWear Armband (BodyMedia, Pittsburgh, PA) was developed to assess TEE, but so far no data have been published in chronic kidney disease patients. The aim of this review is to describe new measurements of energy expenditure and physical activity in chronic kidney disease patients.

Objective: The aim of the present study was to determine the erythrocyte CAI and CAII concentrations in nondialyzed chronic kidney disease patients, and observe the relationship with acidosis, zinc, anemia, and iron supplementation. Methods: Erythrocyte CA concentrations were measured in nondialyzed patients (n = 38) using enzyme-linked immunosorbent assays (ELISA). The zinc concentration was determined by atomic absorption spectrophotometer. Results and conclusions: The CA levels were observed to be increased in the patients. The mean erythrocyte zinc concentration was also high and the levels of zinc in plasma were baseline values. Correlation was found between CAI and erythrocytes Zn (r = 0.46; P = 0.003), but there was no correlation with ferritin or pH and bicarbonate. The CA levels did not change after iron supplementation, but the zinc erythrocyte levels were reduced. It is concluded that the CA erythrocyte concentration in CKD patients is increased but this cannot be explained by iron deficiency or acidosis.

Objective: The purpose of this study was to assess the zinc and iron status in patients with chronic renal failure (CRF) who were not receiving dialysis. Design: Cross-sectional study. Setting: Outclinic patients of the Nephrology Division at Federal University of Sao Paulo. Patients: This study was performed on 29 stable patients with CRF who were not receiving dialysis. Main outcome measure: The parameters for determining iron and zinc status were transferrin saturation, zinc protoporphyrin, serum ferritin, hematocrit, serum iron, total iron binding capacity, erythrocyte, and plasma zinc levels (measured by atomic absorption spectrophotometry). Results: The serum ferritin level was reduced to 85.5 ± 67.1 ng/mL and the zinc protoporphyrin level was high (68 ± 32.9 μmol/mol heme), serum transferrin saturation was 19.9% ± 7.85%, mean serum iron level was 66.6 ± 26.3 μg/dL, and mean total iron binding capacity was 336 ± 45.7 μg/dL. Absolute iron deficiency was found in 34.5% of the patients. Zinc level in erythrocytes was high (50.0 ± 7.2 μg/g hemoglobin), whereas plasma zinc was at a borderline level (74 ± 17.7 μg/dL) when compared with normal values. There were significant correlations among plasma zinc and serum iron and transferrin saturation, zinc erythrocyte, and parameters of iron. Conclusion: These results show that absolute iron deficiency can occur in patients who are not receiving dialysis and that there is an abnormal distribution of zinc levels in these patients. Moreover, a possible relationship between iron deficiency and zinc distribution was observed. © 2002 by the National Kidney Foundation, Inc.

Low protein diet for patients with chronic kidney disease (CKD) during conservative treatment (CT) aims to reduce the progression and symptoms of the CKD. This study aimed to evaluate the glomerular filtration rate (GFR) in patients receiving low protein diet during 3 years (≅ 4 clinic visits per year). The study comprised 321 patients with CKD on CT from a Renal Nutrition Ambulatory of a Federal Lagoa Hospital. All patients received dietary prescription according to NKF-K/DOQI recommendations and the diet adherence was evaluated with patients being asked whether they were adhering to the treatment and through reported dietary intake (2 weekdays and 1 weekend day). Patients were divided in 4 groups: diabetes Mellitus (DM) patients who adhered (G1) and not adhered to the diet (G2), and patients without DM who adhered (G3) and not adhered to the diet (G4). Groups Before After Group 1-DM (n=83) Cr (mg/dL) 1.9 ± 0.6 1.6 ± 0.7* GFR (mL/min) 37.8 ± 14.4 46.6 ± 17.3** Group 2-DM (n=106) Cr (mg/dL) 1.9 ± 0.7 2.03 ± 0.7 GFR (mL/min) 43.8 ± 17.3 42.6 ± 13.3 Group 3-non-DM (n=75) Cr (mg/dL) 2.2 ± 0.8 1.8± 0.8* GFR (mL/min) 34.3 ± 13.1 40.9 ± 21.7 Group 4-non-DM (n=57) Cr (mg/dL) 2.2 ± 0.8 2.4 ± 1.0 GFR (mL/min) 39.9 ± 19.0 35.2 ± 18.4 There was no difference between diabetic and non-diabetic patients who adhered to the diet. Both groups showed improvement on GFR. In conclusion, these analyses suggest that a lower protein intake retards the progression of renal disease.

Elevated serum uric acid has been associated to a variety of cardiovascular disease states and with systemic inflammation. The aim of this study was to analyze the association between uric acid levels and inflammatory markers in hemodialysis (HD) patients. This cross-sectional study included 50 HD patients (62% men, 54.3±12.6 yrs, BMI 24.4±4 Kg/m 2 ) and 21 healthy individuals (45% men, 50.7±15.7 yrs, BMI 25.5±4.0 Kg/m 2 ). Uric acid was measured using uricase-PAP method, inflammatory (TNF-α, IL-6 and CRP) and atherosclerosis markers (ICAM-1, VCAM-1, MCP-1 and PAI-1) were measured by a multiplexed particle-based flow cytometric assay. There was a positive correlation between serum uric acid and inflammatory markers, IL-6 (r=0.30, p=0.01), CRP (r=0.37, p=0.003), TNF-α (r=0.40, p=0.001) and adhesion molecules levels, ICAM-1 (r=0.53, p=0.0001), and VCAM-1 (r=0.45, p=0.0001) Parameters HD Patients Healthy individuals CRP (mg/mL) 0.32 ± 0.30 * 0.11 ± 0.12 TNF-α (pg/mL) 5.5 ± 2.1 * 2.4 ± 1.1 IL-6 (pg/mL) 4.1 ± 1.6 * 2.7 ± 0.4 PAI-1 (ng/mL) 7.0 ± 2.7 6.2 ± 2.1 MCP-1 (pg/ml) 47.6 ± 24.2 37.3 ± 19.0 VCAM-1 (ng/mL) 48.5 ± 8.5 * 23.8 ± 5.5 ICAM-1 (ng/mL) 20.5 ± 15.9 * 7.2 ± 1.2 ⁎ p In conclusion, these original data suggest that uric acid may have a role in inflammation and atherosclerosis in HD patients

Nutritional status is a major determinant of the outcome of hemodialysis (HD) patients. While protein wasting is associated with morbidity and mortality, high fat mass and central adiposity is also observed in HD population and, related to metabolic disorders. Therefore, body composition assessment is a key point to provide adequate nutritional care to these patients. In this way, practical and reliable indicators of body composition are needed for clinical purposes. Thus, the objective of this study was to evaluate the use of anthropometry as an alternative to dual energy X-ray absorptiometry (DXA), considered the reference method to evaluate body fat in HD patients. Thirty-nine HD patients (52.7±11.3 years, 24 men, BMI, 23.7±4.0 kg/m2, urea clearance (Kt/Vsp) of 1.47±0.22 and 64.1±46.1 months on HD) were studied. Percentage of body fat (%BF) was performed by DXA scans (Prodigy Advanc Plus, Lunar Corp, Madison, WI, USA) and anthropometry (biceps, triceps, subscapular and suprailiac skinfold thicknesses) after a HD session. Body density was calculated using the formula of Durnin and Womersley (1974) and the %BF was calculated by Siri´s equation (Siri, 1961). The reference values for %BF were considered (Lohman et al., 1991). The mean of %BF assessed by anthopometry and DXA was 25.2±6.9% and 26.8±8.3% for men and 32.8±6.3% and 31.5±8.7% for women, respectively. The most of HD patients presented high %BF (≥25% for men and ≥32% for women): 59.0% by anthropometry and 56.4% by DXA. The paired analysis showed that the %BF assessment was not different when evaluated by anthropometry or DXA methods (p=0.6). The kappa coefficient between DXA and anthropometry was 0.42 (p

Exercise programs have been recommended as nutritional interventions in hemodialysis (HD) patients to minimize loss of muscle mass, improve physical and functional capacity, inflammation thus controlling or preventing cardiovascular diseases (CVD), which accounts for 50% of mortality in dialysis patients. Therefore the purpose of this study was to analyze the effects of a resistance exercise (RE) program on biochemical parameters, inflammation markers, and body composition in HD patients. Thirty- six HD patients (61.1% men, mean age 46.7±2.5yrs) were studied. The anthropometric and biochemical parameters are presented in Table. There were significant differences after 6 months of RE in albumin and CRP plasma levels and body composition parameters. The HD patients gained nearly 3kg of lean mass and lost about 3% of body fat. Parameters Before(n=30) After(n=30) BMI (kg/m2) 22.8±4.0 23.3±4.3 Arm muscular area (cm) 30.3±13.7 35.4±13.8 * Body Fat (%) 31.5±5.6 28.4±5.9 * Lean mass (kg) 42.4±10.0 45.5±11.0 * Albumin (g/dL) 3.6±0.3 3.8±0.2 * Globulin (g/dL) 3.2±0.3 2.8±0.5 ** Interleukin-6 (pg/mL) 81.3±9.4 78.7±10.4 TNF-α (pg/mL) 25.7±6.5 24.3±8.7 Creatinine (mg/dL) 12.5±3.6 12.2±3.7 CRP (pg/mL) 2.9±0.4 2.0±0.1 * ⁎ p ⁎⁎ p In conclusion, statistically significant improvements were observed in body composition, albumin and CRP levels after 6 months of resistance exercises. Therefore, RE provide better prognosis in HD patients reducing cardiovascular risk, inflammation and loss of muscle mass.

Previous studies have indicated selenium (Se) deficiency in hemodialysis (HD) patients and it may increase the mortality risk for death among hemodialysis patients. Studies from our laboratory showed poor nutritional status of Se in HD patients. The purpose of this study was to evaluate Se levels as predictors of cardiovascular mortality in HD patients. A total of 44 HD patients (53.0±15.0 years old, average time on dialysis 80.1±112.7 months, BMI, 24.6±34.3 kg/m2) from the RenalCor Clinic in Rio de Janeiro, Brazil, were followed up 36 months. The plasma and erythrocyte Se levels were determined by atomic absorption spectrophotometry with hydride generation (Hitachi, Z−500). Associations between Se levels and cardiovascular mortality in HD patients were examined by Cox's regression model. Mean plasma Se was 72.1±70.1 μg/L and erythrocyte Se 194.8±148.91 μg/L and a total of 17 patients died from cardiovascular event during the follow-up period. Analysis by the Cox model showed that only low erythrocyte Se levels were significant predictors of mortality (hazard ratio [HR] 0.995 [95% CI 0.991-0.999]. In conclusion, decreased erythrocyte Se level may increase the risk of death in hemodialysis patients.

Selenium (Se) is a well-known antioxidant with a critical role in the proper functioning of nervous and muscle functions. In the last decade, many authors have suggested that Se may be a potent protective agent for neurons and myocytes through selenoprotein expression in the brain, as well as in skeletal and cardiac muscles. Low Se status has been associated with reduced coordination, motor speed and muscle strength. Reduced muscle function is common in hemodialysis (HD) patients; however, no study evaluated the association between muscle function and Se levels in HD patients. The objective of this study was to correlate muscle function with Se plasma levels in HD patients. Twenty HD patients (12 men, 54.5±15.2 yr; 81.7±52.8 months on HD) from RenalCor Clinic at Rio de Janeiro, Brazil were studied. Blood samples were collected during fasting, before a regular HD session. The Se plasma levels were determined by atomic absorption spectrophotometry with hydride generation (Hitachi, Z-500) and handgrip strength (HGS) was measured three times with a mechanical dynamometer (Jamar) after HD sessions in the non-fistula side and the highest value was used for analysis. HGS values less than the 10 th percentile of an age-, gender- and regional specific reference were considered as muscle function loss. Plasma Se levels (31.9±14.8 μg/L) were below the normal range (60-120 μg/L) and all patients were Se deficient. HGS values were significantly greater in males (31.0±11.5 kg vs 14.0±6.8 kg for females) (p=0.001) and the muscle function loss was observed in 50% of patients and, those with muscle function loss presented low Se levels (26.5±12.1 μg/L) when compared to patients with preserved muscle function (39.12±14.5 μg/L) (p=0.05). These data suggest that Se can have an important role on muscle function in HD patients. However, more research is needed to better understand this possible relationship in CKD patients.

Hemodialysis patients (HD) present inflammation, metabolic acidosis and anorexia which contribute to loss of functional capacity, muscle mass and strength. Resistance training (RT) is recognized to reduce these effects on the musculoskeletal system. This study aimed to evaluate the effects of intradialytic RT on the functional capacity, strength and muscle mass in HD patients. Eighteen HD patients (50% men, 49.3±11.5 years, BMI 22.7±3.9 kg/m2, 63.2±46.3 months on dialysis) exercised 3 times a week for 6 months. All parameters were evaluated before and after 6 months of RT. There were significant changes in the functional tests 10-TSS (10 times Sit-to-Stand Test) and SS-60 (amount of sit to stand in 60 seconds), in the muscle mass and % of body fat after RT. The medial and proximal leg circumferences increased significantly and no differences were observed in torque extensor and flexor and distal leg circumferences. In conclusion, RT contributes to improving body composition and functional capacity of HD patients. Parameters Before RT After RT 10-TSS (seconds) 27.9±6.4 21.9±4.1 * SS-60 (repetitions) 26.0±6.7 28.9±5.7 * Muscle mass - men (kg) 48.0±9.1 51.5±10 * Muscle mass - women (kg) 34.1±4.4 36.9±4.9 * Body fat - men (%) 29.2±5.1 25.3±5.1 * Body fat - women (%) 34.6±5.1 32.4±4.7 * LG- Proximal -R (cm) 53.6±6.6 55.4±6.7 * LG- Proximal -L (cm) 52.7±5.8 54.1±6.7 LG- Medial -R (cm) 46.8±5.1 48.6±4.9 * LG- Medial -L (cm) 46.6±4.4 48.5±5.4 * LG- Leg circumference; R-right; L- left; ⁎ p

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 0.3mg/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.fx1