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Abstract Background Few equations have been developed in veterinary medicine compared to human medicine to predict body composition. The present study was done to evaluate the influence of weight loss on biometry (BIO), bioimpedance analysis (BIA) and ultrasonography (US) in cats, proposing equations to estimate fat (FM) and lean (LM) body mass, as compared to dual energy x-ray absorptiometry (DXA) as the referenced method. For this were used 16 gonadectomized obese cats (8 males and 8 females) in a weight loss program. DXA, BIO, BIA and US were performed in the obese state (T0; obese animals), after 10% of weight loss (T1) and after 20% of weight loss (T2). Stepwise regression was used to analyze the relationship between the dependent variables (FM, LM) determined by DXA and the independent variables obtained by BIO, BIA and US. The better models chosen were evaluated by a simple regression analysis and means predicted vs. determined by DXA were compared to verify the accuracy of the equations. Results The independent variables determined by BIO, BIA and US that best correlated (p r2, 19 equations were selected (12 for FM, 7 for LM); however, only 7 equations accurately predicted FM and one LM of cats. Conclusions The equations with two variables are better to use because they are effective and will be an alternative method to estimate body composition in the clinical routine. For estimated lean mass the equations using body weight associated with biometrics measures can be proposed. For estimated fat mass the equations using body weight associated with bioimpedance analysis can be proposed.

In the pursuit of an effortless "miracle cure", there has been a significant increase in the proliferation of fad diets. These diets generally exclude a food group or macronutrients and may also restrict energy intake; they become popular quickly but often lack substantial scientific evidence to support their efficacy and safety. They only show short-term results rather than promoting a lifestyle change. Fad diets are nutritionally unbalanced and can be dangerous for some individuals. Most fad diets are generally restrictive in carbohydrates, high in protein, or unbalanced and have low energy intake, which can harm patients with early stages of chronic kidney damage (CKD) who need a low-protein diet with adequate energy intake. This narrative review discusses the risk of fad diet prescriptions for non-dialysis CKD patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the effects of an intradialytic aerobic exercise training program on the expression of transcription factors nuclear factor κappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2), related to inflammatory and antioxidant pathways, respectively, in patients with chronic kidney disease (CKD) on hemodialysis., Methods: This was a longitudinal, randomized clinical trial with a washout period and crossover performed with 33 patients randomized into two groups: Exercise (individualized intradialytic aerobic exercise on an adapted stationary exercise bike) three times per week for three months and control (without exercise). After the washout period (1 month), the exercise group became the control, and the other group performed the exercises for another three months. Blood sample collection, food intake, and anthropometry were evaluated at the beginning and end of each study phase. Nrf2, its target gene NAD(P)H quinone oxidoreductase 1 (NQO1), and NF-κB transcription factors were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and the inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) by ELISA assay., Results: Eighteen patients [11 men, 44.1 ± 8.4 years, 17.3 (6.6-124) months on HD] completed all the study. The obtained data revealed that the intervention did not affect Nrf2, NQO1, and NF-κB mRNA expression. Also, TNF-α levels were not changed. However, IL-6 showed a tendency to decrease after the exercise intervention (p = 0.054)., Conclusion: In hemodialysis patients, three months of intradialytic aerobic exercise did not modulate the transcription factors associated with inflammation (NF-κB) and antioxidant activity (Nrf2 and NQO1)., Clinical Trials Registration Number: NCT04375553., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Propolis possesses many bioactive compounds that could modulate the gut microbiota and reduce the production of uremic toxins in patients with chronic kidney disease (CKD) undergoing hemodialysis (HD). This clinical trial aimed to evaluate the effects of propolis on the gut microbiota profile and uremic toxin plasma levels in HD patients. These are secondary analyses from a previous double-blind, randomized clinical study, with 42 patients divided into two groups: the placebo and propolis group received 400 mg of green propolis extract/day for eight weeks. Indole-3 acetic acid (IAA), indoxyl sulfate (IS), and p-cresyl sulfate (p-CS) plasma levels were evaluated by reversed-phase liquid chromatography, and cytokines were investigated using the multiplex assay (Bio-Plex Magpix ® ). The fecal microbiota composition was analyzed in a subgroup of patients ( n = 6) using a commercial kit for fecal DNA extraction. The V4 region of the 16S rRNA gene was then amplified by the polymerase chain reaction (PCR) using short-read sequencing on the Illumina NovaSeq PE250 platform in a subgroup. Forty-one patients completed the study, 20 in the placebo group and 21 in the propolis group. There was a positive correlation between IAA and TNF-α (r = 0.53, p = 0.01), IL-2 (r = 0.66, p = 0.002), and between pCS and IL-7 (r = 0.46, p = 0.04) at the baseline. No significant changes were observed in the values of uremic toxins after the intervention. Despite not being significant, microbial evenness and observed richness increased following the propolis intervention. Counts of the Fusobacteria species showed a positive correlation with IS, while counts of Firmicutes , Lentisphaerae , and Proteobacteria phyla were negatively correlated with IS. Two months of propolis supplementation did not reduce the plasma levels of uremic toxins (IAA, IS, and p-CS) or change the fecal microbiota.

The gut microbiota performs several crucial roles in a holobiont with its host, including immune regulation, nutrient absorption, synthesis, and defense against external pathogens, significantly influencing host physiology. Disruption of the gut microbiota has been linked to various chronic conditions, including cardiovascular, kidney, liver, respiratory, and intestinal diseases. Studying how animals adapt their gut microbiota across their life course at different life stages and under the dynamics of extreme environmental conditions can provide valuable insights from the natural world into how the microbiota modulates host biology, with a view to translating these into treatments or preventative measures for human diseases. By modulating the gut microbiota, opportunities to address many complications associated with chronic diseases appear. Such a biomimetic approach holds promise for exploring new strategies in healthcare and disease management.

Background: Growing evidence suggests that bioactive compounds in berry fruits may mitigate inflammation in patients with chronic kidney disease (CKD)., Objectives: To evaluate cranberry ( Vaccinium macrocarpon ) supplementation effects on modulation of transcription factors involved in inflammation and oxidative stress in nondialysis (stages 3 and 4) patients with CKD. Design/Participants . A randomized, double-blind, placebo-controlled study was performed with 30 patients to receive capsules containing cranberry extract (1000 mg/day) or placebo (1000 mg/day of corn starch) for two months. Measurements . The mRNA expression of nuclear factor-erythroid 2-related factor-2 (Nrf2) and nuclear factor-kB (NF-kB) was evaluated in peripheral blood mononuclear cells (PBMCs) by quantitative real-time polymerase chain reaction. Thiobarbituric acid reactive substances (TBARS) were measured in the plasma to assess oxidative stress. Interleukin-6 (IL-6) plasma levels were assessed by enzyme-linked immunosorbent assay and C-reactive protein (CRP) by immunoturbidimetric method., Results: Twenty-five patients completed the study: 12 in the cranberry group (56.7 ± 7.5 years and body mass index (BMI) of 29.6 ± 5.5 kg/m 2 ) and 13 in the placebo group (58.8 ± 5.1 years and BMI 29.8 ± 5.4 kg/m 2 ). There were no differences in NF-kB or Nrf2 mRNA expressions ( p = 0.99 and p = 0.89) or TBARS, CRP, and IL-6 plasma levels after cranberry supplementation., Conclusions: The cranberry extract administration (1000 mg/day) did not affect Nrf2 and NF-kB mRNA expression, oxidative stress, or inflammatory markers levels in nondialysis CKD patients. This trial is registered with NCT04377919., Competing Interests: The authors declare that they have no conflicts of interest or personal relationships could interfere with the research., (Copyright © 2024 Laís de Souza Gouveia Moreira et al.)

Inflammageing is a persistent low-level inflammatory burden that accompanies age-related dysregulation of the immune system during normative aging and within the diseasome of aging. A healthy diet containing a balanced amount of macronutrients, vitamins and minerals, adequate in calories and rich in poly(phenols), has an essential role in mitigating the effects of inflammageing and extending healthspan through modulation of the activity of a range of factors. These include transcription factors, such as nuclear factor erythroid-derived 2 related factor 2 (Nrf2) and nuclear factor-κB (NF-kB), the inflammasome and the activities of the gut microbiota. The aim of this narrative review is to discuss the potential of food to ameliorate the effects of the diseasome of aging.

Some chronic diseases, including chronic kidney disease (CKD), may be associated with poor outcomes, including a high rate of hospitalization and death after COVID-19 infection. In addition to the vaccination program, diet intervention is essential for boosting immunity and preventing complications. A healthy diet containing bioactive compounds may help mitigate inflammatory responses and oxidative stress caused by COVID-19. In this review, we discuss dietary interventions for mitigating COVID-19 complications, including in persons with CKD, which can worsen COVID-19 symptoms and its clinical outcomes, while diet may help patients with CKD to resist the ravages of COVID-19 by improving the immune system, modulating gut dysbiosis, mitigating COVID-19 complications, and reducing hospitalization and mortality. The concept of food as medicine, also known as culinary medicine, for patients with CKD can be extrapolated to COVID-19 infection because healthy foods and nutraceuticals have the potential to exert an important antiviral, anti-inflammatory, and antioxidant role., (Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Chronic kidney disease is a significant risk factor for cardiovascular disease. In addition to traditional risk factors, such as hypertension, dyslipidemia, diabetes and smoking, patients with chronic kidney disease have a uremic phenotype marked by premature aging, mitochondrial dysfunction, persistent low-grade inflammation, gut dysbiosis and oxidative stress. These complications contribute to abnormal vascular and myocardial remodeling processes, resulting in accelerated vascular calcification, cellular and organ senescence and a high risk of cardiovascular disease. Nonpharmacological strategies, such as increasing physical activity and a healthy diet, may slow the progression of kidney disease and consequently protect the heart. Thus, a deep promotion and advocacy of nutritional guidance based on scientific data is needed. This narrative review discusses how nutritional interventions may delay progressive organ damage in the kidney-heart axis., (Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: Intestinal constipation is a frequent complication in hemodialysis (HD) patients. Polydextrose (PDX), a nondigestible oligosaccharide, has been reported as a fermentable fiber with potential benefits. This study aimed to investigate the possible influence of PDX supplementation on intestinal function in HD patients., Methods: This randomized, double-blind, placebo-controlled trial included 28 patients who received daily oral supplementation with 12 g of PDX or placebo (corn starch) for 2 months. ROME IV criteria were used to define constipation and questionnaires were applied to patient assessment of constipation symptoms (PAC-SYM) and their impact on the patient assessment of constipation quality of life. The Bristol scale was used to assess stool consistency. Commercial Enzyme-Linked Immuno Sorbent Assay kits were used to evaluate the interleukin-6 and tumor necrosis factor-α plasma levels., Results: 25 patients completed the study; 16 in the PDX group [7 females, 48.5 years (IQR = 15.5)] and 9 in the control group [3 females, 44.0 years (IQR = 6.0)]. According to ROME IV criteria, 55% of patients were diagnosed with constipation. PAC-SYM faecal symptoms domain was reduced after 2 months of PDX supplementation (P = .004). We also observed a significant reduction in the PAC-QoL-concerns domain (P = .02). The average values for PAC-SYM and patient assessment of constipation quality of lifewere reduced significantly after intervention with PDX. There were no significant changes after the intervention period concerning biochemical variables, food intake, and inflammation markers. No adverse effects were observed during the supplementation period., Conclusions: The results of the present study suggest that short-term PDX supplementation may have favourable results on intestinal function and the quality of life of chronic kidney disease patients in HD., (Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Residual kidney function for patients with chronic kidney disease (CKD) is associated with better quality of life and outcome; thus, strategies should be implemented to preserve kidney function. Among the multiple causes that promote kidney damage, gut dysbiosis due to increased uremic toxin production and endotoxemia need attention. Several strategies have been proposed to modulate the gut microbiota in these patients, and diet has gained increasing attention in recent years since it is the primary driver of gut dysbiosis. In addition, medications and faecal transplantation may be valid strategies. Modifying gut microbiota composition may mitigate chronic kidney damage and preserve residual kidney function. Although various studies have shown the influential role of diet in modulating gut microbiota composition, the effects of this modulation on residual kidney function remain limited. This review discusses the role of gut microbiota metabolism on residual kidney function and vice versa and how we could preserve the residual kidney function by modulating the gut microbiota balance.

Fish is an excellent source of ω-3 polyunsaturated fatty acids (PUFAs), amino acids, collagen, vitamins, and iodine and its intake is associated with health benefits, mainly reduces risk of cardiovascular mortality. However, recent studies have shown that fish is also an important source of trimethylamine N-oxide (TMAO), a uremic toxin produced by the gut microbiota that promotes an increased risk of cardiovascular diseases. In patients with chronic kidney disease (CKD), TMAO levels are markedly increased due to gut dysbiosis and reduced kidney function. No study has yet evaluated the effects of a fish-rich diet on TMAO plasma levels and cardiovascular outcomes. This review discusses the pros and cons of a fish-rich diet in patients with CKD - a matter of depth., (© 2023 Wiley-VCH GmbH.)

Background and Aims: Several studies have been performed in vitro and in animals showing that propolis (a resin made by bees) has excellent anti-inflammatory properties, but no study has been performed in patients with chronic kidney disease (CKD) on hemodialysis (HD). The present study aimed to evaluate the effects of propolis supplementation on inflammatory markers in patients with CKD on HD., Methods: This is a longitudinal, double-blind, placebo-controlled trial with patients randomized into two groups: propolis (4 capsules of 100 mg/day containing concentrated and standardized dry EPP-AF® green propolis extract) or placebo (4 capsules of 100 mg/day containing microcrystalline cellulose, magnesium stearate and colloidal silicon dioxide) for two months. Routine parameters were analyzed using commercial kits. The plasma levels of inflammatory cytokines were evaluated by flow luminometry., Results: Forty-one patients completed the follow-up, 21 patients in the propolis group (45 ± 12 years, 13 women, BMI, 22.8 ± 3.7 kg/m 2 ) and 20 in the placebo group (45.5 ± 14 years, 13 women, BMI, 24.8 ± 6.8 kg/m 2 ). The obtained data revealed that the intervention with propolis significantly reduced the serum levels of tumour necrosis factor α (TNFα) (p = 0.009) as well as had the tendency to reduce the levels of macrophage inflammatory protein-1β (MIP-1β) (p = 0.07). There were no significant differences in the placebo group., Conclusion: Short-term EPP-AF® propolis dry extract 400 mg/day supplementation seems to mitigate inflammation, reducing the plasma levels of TNFα and MIP-1β in patients with CKD on HD. This study was registered at clinicaltrials.gov (NCT04411758)., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Fermentation has been used since the Early Neolithic period to preserve foods. It has inherent organoleptic and nutritive properties that bestow health benefits, including reducing inflammation and oxidative stress, supporting the growth of salutogenic microbiota, enhancing intestinal mucosal protection and promoting beneficial immunometabolic health effects. The fermentation of food with specific microbiota increases the production salutogenic bioactive compounds that can activate Nrf2 mediated cytoprotective responses and mitigate the effects of the 'diseasome of aging' and its associated inflammageing, which presents as a prominent feature of obesity, type-2 diabetes, cardiovascular and chronic kidney disease. This review discusses the importance of fermented food in improving health span, with special reference to cardiometabolic diseases.

The main goal of this study was to evaluate the reno-protective effects of a phenolic-rich Açaí seed extract (ASE) in mice with kidney failure. Kidney failure was induced chemically with an adenine-rich diet (0.25% w/w for 4 weeks) in male CD1 Swiss mice. Mice were then provided daily with ASE (at a dose of ~ 350 mg/kg/day) in drinking water for 4 weeks. Adenine mice exhibited renal dysfunction evidenced by increased proteinuria, increased uremia, extensive tubular atrophy and kidney fibrosis associated with overexpression of pro-fibrotic genes (collagen 1a1, transforming growth factor β1, TGF-β1) and markers of tubular injury (such as Kidney injury molecule-1, KIM-1). ASE was able to beneficially counteract all these effects. ASE improved oxidative damage and fibrosis by decreasing carbonylated protein and MDA concentrations, as well as collagen deposition in renal tissue. ASE decreased the expression of TGF-β1 gene and the abundance of protein TGF-β1 in kidneys. It further decreased both expression and urinary excretion of tubular injury biomarkers, e.g., KIM-1 and Neutrophil gelatinase-associated lipocalin. CKD ASE-treated mice exhibited higher polyphenol content and total antioxidant capacity compared to control mice. ASE further prevented the expression of profibrotic genes in HK2 human tubular cells exposed to uremic toxins. Taken together, these findings suggest that ASE exerted potent reno-protective and anti-fibrotic effects through its antioxidant activity and the modulation of the TGF-β1 pathway., (© 2022. The Author(s).)

Background: 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., Material and Methods: 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., Results: 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)., Conclusions: 12 weeks of intradialytic aerobic exercise was enough to benefit hemodialysis patients' quality of life, aerobic fitness, and quality of dialysis., Clinicaltrials: gov id: NCT04375553., Competing Interests: Declarations of competing interest All authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Polydextrose (PDX) is a non-digestible oligosaccharide with a complex structure widely used in the food industry. Studies have shown many health benefits of polydextrose, including modulating the gut microbiota, improving the immune system, altering the lipid profile, and stimulating bowel function. Patients with chronic kidney disease (CKD) report gut dysbiosis, inflammation, dyslipidemia and constipation. These are major concerns that affect the quality of life. In this context, PDX can promote beneficial effects. However, little is known about PDX in CKD. This review discusses the possible beneficial effects of PDX on gut health for patients with CKD, particularly its impact on constipation., Competing Interests: Declaration of Competing Interest The authors do not declare any potential conflicts of interest., (Copyright © 2022 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Anemia is one of the most frequent complications in patients with chronic kidney disease (CKD). Despite being multifactorial, the relative or absolute deficiency of erythropoietin production is the leading cause. Recent studies have shown that uremic toxins produced by the gut microbiota also may play a role in the genesis of anemia in these patients., Objective: To evaluate the possible association between uremic toxins plasma levels and anemia in patients with CKD on hemodialysis (HD)., Methods: This cross-sectional study evaluated one hundred fifty-four patients (53.2% men, 51.2 ± 11.2 years, hemoglobin (Hb) levels of 11.2 ± 1.6 g/dL). Biochemical variables such as urea, creatinine, hemoglobin, hematocrit, were measured according to standard methods and uremic toxins such as indoxyl sulfate (IS), indole-3-acetic acid (IAA), p-cresyl sulfate (p-CS) plasma levels were measured by reverse-phase high-performance liquid chromatography (RP-HPLC)., Results: The levels of uremic toxins such as IS, IAA, p-CS were increased in all patients. However, no correlation was found between uremic toxins plasma levels and anemia parameters. Only patients with Hb < 11 g/dL presented a negative correlation between hematocrit and IAA plasma levels., Conclusion: There is no strong evidence that uremic toxins produced by the gut microbiota may be associated with anemia in patients with CKD on HD., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Chronic kidney disease (CKD) manifests with systemic inflammation, oxidative stress, and gut dysbiosis, resulting in metabolic disorders and elevated rates of cardiovascular disease-associated death. These all correlate with a high economic cost to healthcare systems. Growing evidence indicates that diet is an indispensable ally in the prevention and management of CKD and its complications. In this context, the root vegetable beetroot (Beta vulgaris rubra) deserves special attention because it is a source of several bioactive compounds, such as nitrate, betaine, and betalain, and has shown beneficial effects in CKD, including reduction of blood pressure, anti-inflammatory effects, and antioxidant actions by scavenging radical oxidative species, as observed in preclinical studies. Beetroot consumption as a possible therapeutic strategy to improve the clinical treatment of patients with CKD and future directions for clinical studies are addressed in this narrative review., (© The Author(s) 2021. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Regular physical exercise may result in many benefits to patients with chronic kidney disease (CKD) on hemodialysis (HD), including gut microbiota modulation and solute removal. The study aimed to evaluate the effects of two programs of intradialytic exercises on uremic toxins plasma levels in HD patients., Methods: In experiment 1, twenty HD patients [12 men, 44.1 ± 8.9 years, BMI of 23.4 ± 2.4 kg/m 2 ] were randomized into two groups: Aerobic exercise group (AEG, n = 11) that performed aerobic exercise on an adapted exercise bike three times a week for three months (36 sessions) and Control group (CG, n = 9). In experiment 2, twenty-six HD patients [19 men, 47.6 ± 11.0 years, BMI of 25.9 ± 3.6 kg/m 2 ] were randomized into Resistance exercise group (REG, n = 14) that performed a resistance exercise program (using elastic bands and ankle cuffs with both lower limbs) monitored three times a week, during six months (72 sessions) and CG (n = 12). P-cresyl sulfate (p-CS), indoxyl sulfate (IS), and indol-3-acetic acid (IAA) plasma levels were determined by high-performance liquid chromatography (HPLC) with fluorescent detection., Results: The uremic toxins plasma levels did not reduce in both exercise programs, aerobic exercise (IS: 32.7 ± 14.0 vs 33.0 ± 15.4 mg/L, p = 0.86; p-CS: 59.9 ± 39.3 vs 60.0 ± 41.2 mg/L, p = 0.99; IAA: 2233 [1488-2848] vs 2227 [1275-2824] µg/L, p = 0.72) and resistance exercise (IS: 28.3 ± 11.3 vs 29.1 ± 9.7 mg/L, p = 0.77; p-CS: 31.4 ± 21.3 vs 34.2 ± 19.8 mg/L, p = 0.63; IAA: 1628 [1330-3530] vs 2000 [971-3085] µg/L, p = 0.35) in HD patients., Conclusion: According to our findings, physical exercise does not appear to alter the levels of uremic toxins produced by the gut microbiota in HD patients., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

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-h 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., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare., (Copyright © 2021 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Patients with chronic kidney disease (CKD) have several pathophysiological alterations, including anemia, one of the first changes in CKD patients. More recently, researchers have observed that the intestinal microbiota alterations are also another complication in these patients. The most common treatment for anemia is oral (mainly ferrous sulfate) or intravenous iron supplementation. Despite being a necessary treatment, recent studies have reported that supplementation with oral iron may increase its availability in the intestine, leading to disturbance in the gut microbiota and also to oxidative stress in the enterocytes, which may change the permeability and the microbiota profile. Although it is a therapy routinely used in patients with CKD, supplementation with oral iron on the gut microbiota has been rarely studied in these patients. Thus, this review will discuss the relationship between iron and the gut microbiota and the possible effects of oral iron supplementation on gut microbiota in patients with CKD., (© 2021 American Society for Parenteral and Enteral Nutrition.)

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/m 2 , 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/m 2 ) 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., (Copyright © 2020 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

The observation that unhealthy diets (those that are low in whole grains, fruits and vegetables, and high in sugar, salt, saturated fat and ultra-processed foods) are a major risk factor for poor health outcomes has boosted interest in the concept of 'food as medicine'. This concept is especially relevant to metabolic diseases, such as chronic kidney disease (CKD), in which dietary approaches are already used to ameliorate metabolic and nutritional complications. Increased awareness that toxic uraemic metabolites originate not only from intermediary metabolism but also from gut microbial metabolism, which is directly influenced by diet, has fuelled interest in the potential of 'food as medicine' approaches in CKD beyond the current strategies of protein, sodium and phosphate restriction. Bioactive nutrients can alter the composition and metabolism of the microbiota, act as modulators of transcription factors involved in inflammation and oxidative stress, mitigate mitochondrial dysfunction, act as senolytics and impact the epigenome by altering one-carbon metabolism. As gut dysbiosis, inflammation, oxidative stress, mitochondrial dysfunction, premature ageing and epigenetic changes are common features of CKD, these findings suggest that tailored, healthy diets that include bioactive nutrients as part of the foodome could potentially be used to prevent and treat CKD and its complications.

Propolis is a polyphenolic plant resin collected by bees to protect hives against pathogens and temperature drop. It exhibits antibacterial, antioxidant, and antiinflammatory properties. Propolis has been reported to possess antidiabetic properties and display beneficial effects against cardiovascular disease, gut dysbiosis, and chronic kidney disease. It has an excellent clinical safety profile, with no known toxic effects described so far. In this review, we discuss the salutogenic effects of propolis, with particular reference to modulating notable features of chronic kidney disease, notably those involving cardiovascular risks., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Inflammatory and innate immune responses triggered by pathogen-associated and other danger-associated signals emerging during infections, results in the activation of cytosolic inflammasomes. The nod-like receptor pyrin domain containing 3 (NLRP3) is one of the inflammasomes mediating such responses through the activation of caspase-1, which increases the production and release of pro-inflammatory cytokines, such as IL-1β and IL-18 and induces programmed cell death through pyroptosis. NLRP3 is thought to play a crucial role in the underlying inflammatory responses in many lifestyles related chronic diseases. Consequently, research on the NLRP3 inflammasome has expanded dramatically in recent years. Although several studies have investigated the role of NLRP3 activation in chronic kidney disease (CKD), few studies have evaluated strategies to modulate its activation by means of interventions using non-pharmacological strategies. This review discusses some nutritional strategies (bioactive compounds, probiotics and caloric restriction) that have been shown to influence NLRP3 in experimental models of renal disease, and in CKD. It discusses how nutritional interventions could potentially dampen NLRP3 associated inflammatory burden, as part of nutritional strategies to prevent and treat CKD and its complications., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Patients with chronic kidney disease (CKD) present an imbalance of the gut microbiota composition, leading to increased production of uremic toxins like p-cresyl sulfate (PCS), product from bacterial fermentation of the amino acids tyrosine (Tyr) and phenylalanine (Phe) from the diet. Thus, diet may be a determinant in the uremic toxins levels produced by the gut microbiota. The aim of this study was to evaluate the possible relationship between Tyr and Phe intake and PCS plasma levels in non-dialysis CKD patients., Methods: Twenty-seven non-dialysis CKD patients (stages 3 and 4) without previous nutritional intervention were evaluated. The dietary intake was evaluated using a 24-hour recall, 3-day food record and protein intake was also estimated by Protein Nitrogen Appearance (PNA). The plasma levels of PCS were measured using reverse phase high performance liquid chromatography., Results: The evaluated patients (GRF, 34.8 ± 12.4 mL/min, 54.2 ± 14.3 years, BMI, 29.3 ± 6.1 kg/m2) presented mean protein intake of 1.1 ± 0.5 g/kg/day), Tyr of 4.5 ± 2.4 g/day and Phe of 4.6 ± 2.5 g/day. PCS plasma levels (20.4 ± 15.5 mg/L) were elevated and positively associated with both, Tyr (r = 0.58, p = 0.002) and Phe intake (r = 0.53, p = 0.005), even after adjustments for eGFR and age., Conclusion: This study suggests that the diet is an important modulator of the uremic toxins plasma levels produced by the gut microbiota, in non-dialysis CKD patients.

Current data suggest that low skeletal muscle mass provides prognostic information in patients with cancer and may even be considered a biomarker in research and clinical evaluations. The aim of this systematic review was to explore whether low muscle mass is associated with overall survival (OS) in patients with incurable cancer. A systematic search was conducted for published literature using PubMed/MEDLINE, Scopus, LILACS, and the Cochrane Library, with no restrictions on language or publication date, to examine whether low muscle mass is associated with OS in patients with incurable cancer. Eligible studies included low muscle mass evaluated using gold standard techniques (dual energy x-ray absorptiometry or computed tomography). The studies quality assessment was performed using the Newcastle-Ottawa Scale. Thirteen studies were included. The studies reported on 1959 patients between 54.3 (median) and 72.9 (mean) y of age; pancreatic cancer was the most common type of tumor. According to the survival curves and most of the multivariate analyses, there was no statistically significant association between loss of muscle mass and reduced OS. Four studies reported that overweight or obese patients with muscle mass depletion had significantly shorter OS. These results indicate that there is insufficient evidence to associate low muscle mass with OS in patients with incurable cancer. Further studies deploying other muscle measurement methods suggest that use of low muscle mass cutoff alone is still necessary in the pursuit of OS prediction in this population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: In chronic kidney disease (CKD) patients, dysbiosis is associated with inflammation and cardiovascular risk, so many nutritional strategies are being studied to reduce these complications. Resistant starch (RS) can be considered a prebiotic that promotes many benefits, including modulation of gut microbiota which is linked to immune-modulatory effects. The aim of this study was to evaluate the effects of RS supplementation on proinflammatory cytokines in CKD patients on hemodialysis (HD)., Methods: A double-blind, placebo-controlled, randomized trial was conducted with sixteen HD patients (55.3 ± 10.05 years, body mass index (BMI) 25.9 ± 5.42 kg/m 2 , 56% men, time on dialysis 38.9 ± 29.23 months). They were allocated to the RS group (16 g RS/day) or placebo group (manioc flour). The serum concentration of ten cytokines and growth factors was detected through a multiparametric immunoassay based on XMap-labeled magnetic microbeads (Luminex Corp, USA) before and after 4 weeks with RS supplementation., Results: After RS supplementation, there was a reduction of Regulated upon Activation, Normal T-Cell Expressed and Secreted (p < 0.001), platelet-derived growth factor (two B subunits) (p = 0.014) and interferon-inducible protein 10 (IP-10) (p = 0.027). The other parameters did not change significantly., Conclusion: This preliminary result indicates that RS may contribute to a desirable profile of inflammatory markers in CKD patients.

Patients with chronic kidney disease (CKD) present many complications that potentially could be linked to increased cardiovascular mortality such as inflammation, oxidative stress, cellular senescence and gut dysbiosis. There is growing evidence suggesting that nutritional strategies may reduce some of these complications. Clinical studies suggest that supplementation of cranberries may have beneficial effects on human health such as prevention of urinary tract infections. More recently, the anti-inflammatory and anti-oxidant effects as well as modulation of gut microbiota provided by cranberry phytochemicals have drawn more attention. A better understanding of possible effects and mechanisms of action of cranberry supplementation in humans could inform researchers about warranted future directions for clinical studies targeting these complications in CKD patients by applying nutritional strategies involving cranberry supplementation.

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/m 2 , 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 × 10 13 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.

Recent studies have suggested that uremic toxins such as indoxyl sulfate (IS) and indole-3-acetic acid (IAA) from the metabolism of the gut microbiota may be involved in the inflammatory signaling pathway in chronic kidney disease (CKD) patients through the activation of the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor. The objective of this study was to investigate the possible relationship between uremic toxins (IS and IAA) and AhR protein expression in CKD patients. A cross-sectional observational study involving 17 hemodialysis (HD) [11 men, 55.5 ± 11.7 years of age, 54.0 (25.5-136.0) months of HD, body mass index (BMI) of 25.8 ± 3.8 kg/m 2 ] and 15 non-dialysis-dependent (NDD) CKD (8 men, 54.1 ± 18.2 years of age, glomerular filtration rate of 34.8 ± 21.0 mL/min/1.73 m 2 , BMI of 27.4 ± 5.0 kg/m 2 ) patients was conducted. IS and IAA levels were measured by reversed-phase high-performance liquid chromatography, and the protein expression levels of AhR and nuclear factor κ B (NF-κB) were evaluated by a Western blot assay. There was no difference in the expression of either AhR or NF-κB in the patients, and as expected, uremic toxin levels were higher in HD patients than in NDD patients. In the overall analysis, AhR protein expression was positively associated with IAA plasma levels ( r = 0.4; p = 0.03) and NF-κB protein expression ( r = 0.62; p = 0.001). Although the role of AhR in inflammation and CVD in CKD patients is far from being completely understood, the association between IAA and AhR observed in this study suggests a possible role for uremic toxins in the cell signaling pathway involved in inflammation in CKD patients.

Introduction: Indoxyl sulfate (IS) and p-cresyl sulfate (p-CS) are albumin-bound uremic toxins that are difficult to remove by hemodialysis (HD). Human serum albumin (HSA) carries several compounds, including fatty acids that can bind to site II of HSA and represent competing ligands for uremic toxins. The aim of this study was to investigate the association between fatty acids and uremic toxin plasma levels in patients undergoing HD., Methods: Thirty-three HD patients (51.5% male, 54.9 ± 10.2 years old, 44.63 ± 28.4 months on HD, albumin level of 3.8 ± 0.3 g/dL) were evaluated. The erythrocyte fatty acid content (saturated fatty acid [SFA], monounsaturated fatty acid [MUFA], and polyunsaturated fatty acid [PUFA]) was measured by gas chromatography, and total IS and p-CS plasma levels were measured by reversed-phase high-performance liquid chromatography., Findings: The mean percentages of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) + DHA and gamma-linolenic (GLA) acid in the erythrocyte membrane were 1.35% ± 0.74%, 1.85% ± 0.79%, and 0.33% ± 0.26%, respectively. The mean levels of IS and p-CS were 19.4 ± 11.9 mg/dL and 101.5 ± 57.2 mg/dL, respectively. There was no significant association between SFA and MUFA and IS and p-CS; however, a negative correlation was found between p-CS and specific PUFAs, and the association between GLA and p-CS levels was retained after adjusting for potential confounding variables (β = -0.49, P = 0.007)., Discussion: Polyunsaturated fatty acids may contribute to the decrease in p-CS uremic toxin plasma levels in patients with chronic kidney disease undergoing HD., (© 2019 International Society for Hemodialysis.)

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., (© 2019 American Society for Nutrition.)

An imbalance of gut microbiota is considered a new cardiovascular risk factor for chronic kidney disease (CKD) patients, since it is directly associated with increased uremic toxin production, inflammation and oxidative stress. Strategies such as prebiotic supplementation have been suggested to mitigate these complications. We hypothesized that prebiotic-resistant starch could ameliorate uremic toxins levels, oxidative stress, and inflammatory states in hemodialysis (HD) patients. This pilot study evaluated 31 HD patients assigned to either resistant starch (16 g of resistant starch Hi-Maize® 260) or placebo (manioc flour) supplementation, which they received for 4 weeks on alternate days through cookies on dialysis days and powder in a sachet on non-dialysis days. Levels of interleukin (IL)-6, high-sensitive C-reactive protein, thiobarbituric acid reactive substances plasma (TBARS), protein carbonylation, indoxyl sulfate (IS) and p-cresyl sulfate were measured. Anthropometric and biochemical parameters, as well as, food intake were also evaluated. As expected, resistant starch group increased fiber intake (p > 0.01), in addition the prebiotic supplementation reduced IL-6 (p = 0.01), TBARS (p > 0.01), and IS (p > 0.01) plasma levels. No significant differences were evident in the placebo group. Prebiotic-resistant starch supplementation seems to be a promising nutritional strategy to improve inflammation, oxidative stress and to reduce IS plasma levels in CKD patients on HD.

Açai (Euterpe oleracea Mart.) fruit from the Amazon region in Brazil contains bioactive compounds such as α-tocopherol, anthocyanins (cyanidin 3-glycoside and cyanidin 3-rutinoside), and other flavonoids with antioxidant and anti-inflammatory properties. Moreover, the prebiotic activity of anthocyanins in modulating the composition of gut microbiota has emerged as an additional mechanism by which anthocyanins exert health-promoting effects. Açai consumption may be a nutritional therapeutic strategy for chronic kidney disease (CKD) patients since these patients present with oxidative stress, inflammation, and dysbiosis. However, the ability of açai to modulate these conditions has not been studied in CKD, and this review presents recent information about açai and its possible therapeutic effects in CKD.

Chronic kidney disease (CKD), which affects 10%-15% of the population, associates with a range of complications-such as cardiovascular disease, frailty, infections, muscle and bone disorders and premature ageing-that could be related to alterations of mitochondrial number, distribution, structure and function. As mitochondrial biogenesis, bioenergetics and the dynamic mitochondrial networks directly or indirectly regulate numerous intra- and extracellular functions, the mitochondria have emerged as an important target for interventions aiming at preventing or improving the treatment of complications in CKD. In this review, we discuss the possible role of bioactive food compounds and exercise in the modulation of the disturbed mitochondrial function in a uraemic milieu., (© 2018 Stichting European Society for Clinical Investigation Journal Foundation.)

Introduction: Cloning via somatic cell nuclear transfer (SCNT) has been associated with a variety of pathologies, primarily in the placenta, and these alterations may be associated with aberrant epigenetic reprogramming of the donor cell genome. We tested the hypothesis that DNA methylation patterns are not appropriately established after nuclear transfer and that those altered patterns are associated with specific aberrant phenotypes., Methods: We compared global and specific placental DNA methylation patterns between aberrant and healthy SCNT-produced calves. Foetal cotyledon samples of ten SCNT pregnancies were collected. Global DNA methylation and hydroxymethylation levels were measured using an ELISA-based assay and specific DNA methylation of satellite I, and α-satellite repeat elements were measured using bisulfite PCR., Results: Our analysis revealed that the SCNT-produced calves, which showed aberrant phenotypes, exhibited a reduced methylation pattern of the satellite I region compared to that of healthy calves. In contrast, global methylation and hydroxymethylation analyses showed higher levels for both cytosine modifications in SCNT-produced female calves with aberrant phenotypes. The satellite I region showed most of the sequences to be hypermethylated in live cloned calves compared with those in deceased calves., Discussion: Our results suggest that this satellite I region could be used as an epigenetic biomarker for predicting offspring viability. Studies evaluating DNA methylation patterns of this satellite region in the donor cell genome or embryo biopsies could shed light on how to improve the efficiency of SCNT cloning., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Uremic toxins produced by gut microbiota (indoxyl sulfate-IS, p-cresyl sulfate-p-CS, and indole-3-acetic acid-IAA) accumulate in hemodialysis (HD) patients and exhibit potent inflammatory effects. However, the impact of these toxins on nuclear E2-related factor 2 (Nrf2) and nuclear factor-kappa B (NF-κB) expression in HD patients remains poorly defined. The aim of this study was to evaluate the association between uremic toxins and Nrf2/NF-κB expression in vitro (RAW 264.7 macrophage-like cells) and in peripheral blood mononuclear cells from HD patients., Methods: Uremic toxins, C-reactive protein (CRP), interleukin-6 (IL-6) and malondialdehyde (MDA) levels were measured in fifteen HD patients and nine healthy individuals. RAW 264.7 macrophage-like cells were incubated with IS, as a prototype of protein-bound uremic toxin. Nrf2 and NF-κB expressions were analyzed by RT-qPCR., Results: HD patients presented high levels of inflammatory markers, MDA and uremic toxins. In addition, they presented high NF-κB and low Nrf2 expression. Uremic toxins were positively correlated with NF-κB expression (IS, ρ = 0.58, p < 0.003; p-CS, ρ = 0.71, p < 0.001; IAA, ρ = 0.62, p < 0.001) and negatively with Nrf2 (IS, ρ = - 0.48, p = 0.01; p-CS, ρ = - 0.46, p < 0.02). Uremic toxins also exhibited positive correlations with CRP and MDA levels. Multivariate analysis revealed that p-CS is a determinant factor of NF-κB expression. In RAW 264.7 culture, NF-κB mRNA expression was stimulated by IS, while Nrf2 was downregulated., Conclusions: Thus, uremic toxins may stimulate NF-κB mRNA and decrease Nrf2 expression in HD patients and, consequently, trigger inflammation and oxidative stress.

Objective: The objective of the study was to evaluate the effects of probiotic supplementation on the gut microbiota profile and inflammatory markers in chronic kidney disease patients undergoing maintenance hemodialysis (HD)., Design and Methods: This was a randomized, double-blind, placebo-controlled study. Forty-six HD patients were assigned to receive 1 of 2 treatments: probiotic (n = 23; Streptococcus thermophilus, Lactobacillus acidophilus e Bifidobacterialongum, 90 billion colony-forming units per day) or placebo (n = 23) daily for 3 months. Blood and feces were collected at baseline and after intervention. The inflammatory markers (C-reactive protein and interleukin-6) were analyzed by immunoenzymatic assay (enzyme-linked immunosorbent assay). Uremic toxins plasma levels (indoxyl sulfate, p-cresyl sulfate, and indole-3-acetic acid) were obtained by Reversed-Phase High-Performance Liquid Chromatography. Routine laboratory parameters were measured by standard techniques. Fecal pH was measured by the colorimetric method, and the gut microbiota profile was assessed by Denaturing Gradient Gel Electrophoresis analysis., Results: Sixteen patients remained in the probiotic group (11 men, 53.6 ± 11.0 year old, 25.3 ± 4.6 kg/m 2 ) and 17 in the placebo group (10 men, 50.3 ± 8.5 year old, 25.2 ± 5.7 kg/m 2 ). After probiotic supplementation there was a significant increase in serum urea (from 149.6 ± 34.2 mg/dL to 172.6 ± 45.0 mg/dL, P = .02), potassium (from 4.4 ± 0.4 mmol/L to 4.8 ± 0.4 mmol/L, P = .02), and indoxyl sulfate (from 31.2 ± 15.9 to 36.5 ± 15.0 mg/dL, P = .02). The fecal pH was reduced from 7.2 ± 0.8 to 6.5 ± 0.5 (P = .01). These parameters did not change significantly in placebo group. Changes in the percentage delta (Δ) between groups were exhibited with no statistical differences observed. The inflammatory markers and gut profile were not altered by supplementation., Conclusions: Aprobiotic supplementation failed to reduce uremic toxins and inflammatory markers. Therefore, probiotic therapy should be chosen with caution in HD patients. Further studies addressing probiotic therapy in chronic kidney disease patients are needed., (Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

In social insects, juvenile hormone (JH) has acquired novel functions related to caste determination and division of labor among workers, and this is best evidenced in the honey bee. In contrast to honey bees, stingless bees are a much more diverse group of highly eusocial bees, and the genus Melipona has long called special attention due to a proposed genetic mechanism of caste determination. Here, we examined methyl farnesoate epoxidase (mfe) gene expression, encoding an enzyme relevant for the final step in JH biosynthesis, and measured the hemolymph JH titers for all life cycle stages of Melipona scutellaris queens and workers. We confirmed that mfe is exclusively expressed in the corpora allata. The JH titer is high in the second larval instar, drops in the third, and rises again as the larvae enter metamorphosis. During the pupal stage, mfe expression is initialy elevated, but then gradually drops to low levels before adult emergence. No variation was, however, seen in the JH titer. In adult virgin queens, mfe expression and the JH titer are significantly elevated, possibly associated with their reproductive potential. For workers we found that JH titers are lower in foragers than in nurse bees, while mfe expression did not differ. Stingless bees are, thus, distinct from honey bee workers, suggesting that they have maintained the ancestral gonadotropic function for JH. Hence, the physiological circuitries underlying a highly eusocial life style may be variable, even within a monophyletic clade such as the corbiculate bees., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor involved in the expression of xenobiotic-metabolizing enzymes, inflammatory cytokines and adhesion molecules. Uremic toxins such as indoxyl sulfate and indole acetic acid are derived from tryptophan fermentation by gut microbiota; they accumulate in patients with chronic kidney disease (CKD) on haemodialysis and have recently emerged as potent ligands of AhR. Therefore, AhR can serve as a mediator in inflammation and cardiovascular diseases in these patients. This review discusses current data that support a link between AhR activation and uremic toxins from gut microbiota in CKD., (© 2017 S. Karger AG, Basel.)

Stingless bees of the genus Melipona, have long been considered an enigmatic case among social insects for their mode of caste determination, where in addition to larval food type and quantity, the genotype also has a saying, as proposed over 50 years ago by Warwick E. Kerr. Several attempts have since tried to test his Mendelian two-loci/two-alleles segregation hypothesis, but only recently a single gene crucial for sex determination in bees was evidenced to be sex-specifically spliced and also caste-specifically expressed in a Melipona species. Since alternative splicing is frequently associated with epigenetic marks, and the epigenetic status plays a major role in setting the caste phenotype in the honey bee, we investigated here epigenetic chromatin modification in the stingless bee Melipona scutellaris. We used an ELISA-based methodology to quantify global methylation status and western blot assays to reveal histone modifications. The results evidenced DNA methylation/demethylation events in larvae and pupae, and significant differences in histone methylation and phosphorylation between newly emerged adult queens and workers. The epigenetic dynamics seen in this stingless bee species represent a new facet in the caste determination process in Melipona bees and suggest a possible mechanism that is likely to link a genotype component to the larval diet and adult social behavior of these bees.

Introduction: Gut microbiota is involved in generation of uremic toxins in chronic kidney disease (CKD) patients on hemodialysis (HD), like indoxyl sulfate (IS) that is originated from tryptophan amino acid fermentation., Objective: To evaluate the tryptophan intake by chronic renal failure patients on HD and its possible relationship with IS plasma levels., Methods: Participated of the study 46 patients with CKD on HD regular program (56.5% men; 52.7 ± 10.3 years; 63 (32.2-118.2) months on HD; BMI 25.6 ± 4.9 kg/m2). The tryptophan intake was evaluated by a 24-hours dietary recall (R-24h) performed on 3 different days. Routine biochemical tests and anthropometric measurements were evaluated. IS plasma levels were determined by High Performance Liquid Chromatography (HPLC) with fluorescent detection and the interleukin-6 (IL-6) plasma levels by immunoenzymatic method (ELISA, Enzyme Linked Immunosorbent Assay)., Results: The average of tryptophan intake was according to recommendation, but IS plasma levels (35.0 ± 11.9 mg/L) were elevated, however according to the EUTox values for uremic individuals. There was no correlation between the tryptophan intake and IS plasma levels. However, there was positive correlation between protein intake and tryptophan and variables used to evaluate lean body mass, and moreover, IS levels were positively associated with IL-6 (r = 0.6: p = 0.01)., Conclusion: The present study suggests that tryptophan dietary intake may not be a determinant factor to IS levels. However, it suggests that gut microbiota may play an important role in systemic inflammation in patients with CKD.

Objective: Protein-bound uremic toxins from gut microbiota tend to accumulate in chronic kidney disease (CKD) patients and are poorly removed by current dialysis techniques. These toxins induce inflammation and are associated with cardiovascular disease (CVD). The aim of this study was to report the relationship between uremic toxins and inflammatory and cardiovascular markers in CKD patients., Design: This was a cross sectional study., Subjects: Twenty-one nondialysis patients were included (43% men, 63.0 ± 7.8 years, glomerular filtration rate: 34.4 ± 12.5 mL/min) as well as 29 hemodialysis (HD) patients [58% men, 52.7 ± 10.3 years, time on dialysis 54 (31-94.5 months)]., Main Outcome Measure: Total levels of uremic toxins (IS, p-CS, and IAA) were assessed by high-performance liquid chromatography with fluorescence detection. C-reactive protein, Interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and calprotectin plasma levels were determined by immunometric assays., Results: HD patients presented higher inflammatory markers and uremic toxins levels than nondialysis patients. IL-6 levels were positively correlated with IS (r = 0.49; P = .03), p-CS (r = 0.35; P = .04) and IAA (r = 0.36; P = .03). A positive correlation was also observed between MCP-1 levels with IS (r = 0.72; P = .001), p-CS (r = 0.48; P = .001) and IAA (r = 0.75; P = .0001). Linear regression showed that IS was an independent predictor for IL-6 and MCP-1 levels after adjustment., Conclusion: Plasma uremic toxins were associated with higher IL-6 and MCP-1 levels in CKD patients, potentially playing a role in the development of CVD., (Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)