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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.

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.

Coffee is a beverage consumed globally. Although few studies have indicated adverse effects, it is typically a beneficial health-promoting agent in a range of diseases, including depression, diabetes, cardiovascular disease, and obesity. Coffee is rich in caffeine, antioxidants, and phenolic compounds, which can modulate the composition of the gut microbiota and mitigate both inflammation and oxidative stress, common features of the burden of lifestyle diseases. This review will discuss the possible benefits of coffee on complications present in patients with diabetes, cardiovascular disease and chronic kidney disease, outwith the social and emotional benefits attributed to caffeine consumption.

This narrative review aimed to explore the functions of betaine and discuss its role in patients with chronic kidney disease (CKD).Some studies on CKD animal models have shown the benefits of betaine supplementation, including decreased kidney damage, antioxidant recovery status, and decreased inflammation. Betaine (N-trimethylglycine) is an N-trimethylated amino acid with an essential regulatory osmotic function. Moreover, it is a methyl donor and has anti-inflammatory and antioxidant properties. Additionally, betaine has positive effects on intestinal health by regulating the osmolality and gut microbiota. Due to these crucial functions, betaine has been studied in several diseases, including CKD, in which betaine plasma levels decline with the progression of the disease. Low betaine levels are linked to increased kidney damage, inflammation, oxidative stress, and intestinal dysbiosis. Furthermore, betaine is considered an essential metabolite for identifying CKD stages.

BACKGROUND AND AIMS Inflammation and oxidative stress are involved in the mortality of patients with chronic kidney disease (CKD) on peritoneal dialysis (PD). In this context, propolis may mitigate inflammation, reducing mRNA expression of nuclear factor-kB (NF-kB) and levels of inflammatory markers as tumor necrosis factor-α (TNF-α). Several studies have been performed in vitro and in animals showing that propolis (a resin made by bees) has excellent anti-inflammatory properties. Only one study evaluated the effects of propolis in patients with CKD (stages 3 and 4) and showed a reduction in proteinuria and urinary MCP-1, but there is no study in patients with CKD on peritoneal dialysis (PD). The present study aimed to evaluate the effects of propolis supplementation on inflammatory markers in patients with CKD on PD. METHODS This is a longitudinal, randomized, double-blind, placebo-controlled trial with 19 patients randomized into two groups: propolis (4 capsules of 500 mg/day containing concentrated and standardized dry EPP-AF® green propolis extract) or placebo (4 capsules of 500 mg/day of magnesium stearate, silicon dioxide and microcrystalline cellulose as placebo) for 2 months. The inflammatory cytokines plasma levels such as TNF-α and interleukin-6 (IL-6) were evaluated by ELISA, and quantitative real-time PCR analyses were performed to evaluate the mRNA expression of NF-kB in peripheral blood mononuclear cells (PBMCs). Plasma malondialdehyde (MDA) levels, a peroxidation lipid marker, was measured as thiobarbituric acid reactive substances (TBARS). Routine parameters, including C-reactive protein (CRP), were analyzed using commercial kits. RESULTS All patients concluded the study: 10 patients in the propolis group [57.2 ± 13.7 years, five men, 6 (6–36) months on DP] and 9 in the placebo group [56.6 ± 14.7 years, two men, 6 (6–57) months on DP]. The obtained data revealed that the intervention did not affect the mRNA expression of NF-κB. However, the plasma levels of TNF-α reduced significantly after propolis supplementation (Table 1 and Fig. 1). There were no significant differences in the placebo group. CONCLUSION Short-term EPP-AF® propolis dry extract supplementation seems to mitigate inflammation, reducing the plasma levels of TNF-α in patients with CKD on PD.

BACKGROUND AND AIMS Patients with chronic kidney disease (CKD), especially on hemodialysis (HD), have a high prevalence of cardiovascular mortality, with oxidative stress (OE) and inflammation as the main contributors. Persistent inflammation from the early stages of CKD is caused by several factors, including increased production of reactive oxygen species (ROS), leading to OE, which in turn induces inflammation by activating the nuclear factor-kB pathway, causing the overproduction of inflammatory cytokines such as tumour necrosis factor-alpha (TNF-α) and interleukins (IL). Dark chocolate is rich in polyphenols, which have antioxidant, anti-inflammatory and cardioprotective properties, and it could be an alternative nonpharmacological to mitigate inflammation and complications of CKD. Therefore, this study aimed to evaluate the effects of dark chocolate on oxidative stress and inflammation in patients with CKD on HD. METHODS This is a longitudinal clinical trial performed with 46 patients with CKD on a regular dialysis program (3 dialysis sessions per week). A group received 40 g of dark chocolate during HD sessions, totaling 120 g per week, for 2 months, and a group did not receive any intervention. Plasma levels of TNF-α and IL-6 were evaluated using the ELISA method. Thiobarbituric acid reactive substances were performed to evaluate lipid peroxidation as malondialdehyde (MDA). Routine parameters were also analyzed using commercial kits. Changes in parameters were evaluated between the pre- and post-treatment. RESULTS Thirty-five patients performed the chocolate group (18 men, 53.4 ± 12.9 years old and 43.2 ± 30 months on HD) and 11 patients (7 men, 46.7 ± 10.9 years old and 55.2 ± 18.7 months on HD) the control group. Although TNF-α plasma levels did not reduce significantly after chocolate, the levels were increased in the control group (Table 1 and Fig. 1). The potassium plasma levels were reduced (from 5.9 ± 0.8 to 5.5 ± 0.8 mg/dL, P CONCLUSION Two months of dark chocolate intervention seem to modulate the TNF-α plasma levels (inflammation marker) in patients with CKD on hemodialysis. It is important to emphasize that dark intervention in this study did not increase the phosphorus plasma levels in patients with CKD on HD.

BACKGROUND AND AIMS BTB and CNC homology 1 (Bach1) is a protein into the cells that antagonizes the actions of nuclear factor erythroid 2-related factor-2 (Nrf2), a master regulator of cytoprotective responses. Bach1 binds to genomic DNA and can inhibit the synthesis of antioxidant enzymes, increasing inflammation. Bach1 may be a therapeutic target to mitigate inflammation in patients with chronic kidney disease (CKD). However, no clinical study has been reported on Bach1 in patients with CKD. This study aimed to evaluate Bach1 mRNA expression in different treatments of CKD, including patients on conservative treatment (non-dialysis), hemodialysis (HD) and peritoneal dialysis (PD). METHODS Twenty patients on HD (54.3 ± 13.7 years old, nine men), fifteen on PD (51.4 ± 14.9 years old, eight men) and thirteen non-dialysis patients (61.0 ± 6.9 years old, seven men, estimated glomerular filtration rate of 39.2 ± 9.6 mL/min/1.73 m2) were enrolled in the study. The peripheral blood mononuclear cells were isolated and processed to evaluate the expression of nuclear factor-kB (NF-kB), Nrf2 and Bach1 by quantitative real-time polymerase chain reaction. Malondialdehyde (MDA), a lipid peroxidation marker, and C-reactive protein (CRP) plasma levels were also measured. RESULTS Bach1 mRNA expression was significantly higher in patients on hemodialysis (P CONCLUSION Patients with CKD on HD patients seem to have upregulation of Bach1 mRNA expression compared to patients on conservative and DP treatment. The associations among Nrf2 and Bach1 expressions in these patients deserve further investigation.

Sulforaphane (SFN) is a sulfur-containing isothiocyanate found in cruciferous vegetables (Brassicaceae) and a well-known activator of nuclear factor-erythroid 2-related factor 2 (Nrf2), considered a master regulator of cellular antioxidant responses. Patients with chronic diseases, such as diabetes, cardiovascular disease, cancer, and chronic kidney disease (CKD) present with high levels of oxidative stress and a massive inflammatory burden associated with diminished Nrf2 and elevated nuclear transcription factor-κB-κB expression. Because it is a common constituent of dietary vegetables, the salutogenic properties of sulforaphane, especially it’s antioxidative and anti-inflammatory properties, have been explored as a nutritional intervention in a range of diseases of ageing, though data on CKD remain scarce. In this brief review, the effects of SFN as a senotherapeutic agent are described and a rationale is provided for studies that aim to explore the potential benefits of SFN-rich foods in patients with CKD.

Alkaline phosphatase (AP) is a ubiquitous membrane-bound glycoprotein that catalyzes phosphate monoesters' hydrolysis from organic compounds, an essential process in cell signaling. Four AP isozymes have been described in humans, placental AP, germ cell AP, tissue nonspecific AP, and intestinal AP (IAP). IAP plays a crucial role in gut microbial homeostasis, nutrient uptake, and local and systemic inflammation, and its dysfunction is associated with persistent inflammatory disorders. AP is a strong predictor of mortality in the general population and patients with cardiovascular and chronic kidney disease (CKD). However, little is known about IAP modulation and its possible consequences in CKD, a disease characterized by gut microbiota imbalance and persistent low-grade inflammation. Mitigating inflammation and dysbiosis can prevent cardiovascular complications in patients with CKD, and monitoring factors such as IAP can be useful for predicting those complications. Here, we review IAP's role and the results of nutritional interventions targeting IAP in experimental models to prevent alterations in the gut microbiota, which could be a possible target of predictive, preventive, personalized medicine (PPPM) to avoid CKD complications. Microbiota and some nutrients may activate IAP, which seems to have a beneficial impact on health; however, data on CKD remains scarce.

International audience; BACKGROUND AND OBJECTIVES: Recent studies have shed light on the potential role of curcumin in mitigating inflammation in patients with chronic kidney disease (CKD). This study aimed to evaluate the effects of curcumin supplementation on plasma levels of markers of inflammation and oxidative stress in patients with CKD undergoing hemodialysis (HD). METHODS: These are secondary exploratory analyses from a previous double-blind, randomized controlled pilot study registered under ClinicalTrials.gov Identifier no. NCT00123456. It included 28 hemodialysis patients from a previous study divided into two groups: curcumin group (receiving juice with 2.5 g of turmeric 3×/week for 12 weeks) and a control group. The TNF-α, IL-6 and Ox-LDL plasma levels were measured by sandwich enzyme immunoassays ELISA; lipid peroxidation was measured by the reaction between malondialdehyde (MDA) and thiobarbituric acid. RESULTS: After 12 weeks of supplementation with curcumin, the TNF-α plasma levels were significantly reduced [from 15.0 (8.23-73.3) to 6.17 (1.11-55.0) pg/mL, p = 0.01]. CONCLUSION: 12 weeks of treatment with curcumin in HD patients resulted in a reduction in the biomarker of inflammation (TNF-α), confirming our previous hypothesis that curcumin has an anti-inflammatory effect.

International audience; No abstract available

Garlic, a member of the Allium family, widely used in cooking for many centuries, displays well described antioxidant and anti-inflammatory properties, as a result of its constituent organosulfur compounds, such as alliin, allicin, ajoene S-allyl-cysteine, diallyl sulfide and diallyl disulfide, among others. Although garlic has demonstrated beneficial effects in cardiovascular disease, diabetes, and cancer, its efficacy as a therapeutic intervention in chronic kidney disease remains to be proven. This review thus focuses on the potential benefits of garlic as a treatment option in chronic kidney disease. and its ability to mitigate associated cardiovascular complications and gut dysbiosis.

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.

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.

Introduction: The mortality of the population with chronic kidney disease (CKD) on hemodialysis (HD) is very high and the protein-energy malnutrition stands out as one of the most common consequences in relation to this condition. Objective: To evaluate the association between time of hemodialysis and nutritional parameters of patients. Methods: It is a cross-sectional study with secondary data, developed of the University Hospital of the Federal University of Juiz de Fora (HU/UFJF). This study was approved by the Research Ethics Committee (Nº 1.233.142), a total of 36 patients. The medical records and collected data were analyzed for anthropometric markers, biochemical and diet, considering two groups: HD time less than three and greater than or equal to three years. Results: There was reduction of mass of somatic protein with increased duration of HD. In relation to food intake was observed that in patients with increased duration of dialysis, an increase in average consumption of protein / kg of weight, calories, phosphorus and potassium, with a significant difference from the mean protein intake / kg (p = 0.04) and phosphorus (p = 0.045). Increasing HD time has altered body composition of patients, indicating a decline in the nutritional status of these individuals. Conclusion: HD patients are a risk group for protein-energy malnutrition, where HD time interferes with the nutritional status and food profile of the patient. The group HD time greater than or equal to 3 years presented worsening nutritional status. Resumo Introdução: Pacientes com doença renal crônica em hemodiálise (HD) apresentam risco elevado para mortalidade, sendo que a desnutrição protéico-energética se destaca como uma das causa mais comuns em relação a essa condição. Objetivo: Avaliar a associação entre o tempo de hemodiálise e parâmetros nutricionais dos pacientes. Métodos: É um estudo transversal com dados secundários, desenvolvido no Hospital Universitário Federal Universidade de Juiz de Fora (HU / UFJF). Este estudo foi aprovado pela pesquisa Comitê de Ética (nº 1.233.142), um Total de 36 pacientes. Os dados foram coletados por meio dos prontuários médicos, os quais foram analisados marcadores antropométricos, bioquímicos e dieta, considerando dois grupos: tempo HD menor do que três anos e tempo de HD maior ou igual atrês anos. Resultados: Houve redução de massa de proteína somática com aumento do tempo em HD. Em relação à avaliação alimentar, observou-se que em pacientes com maior tempo em diálise houve aumento no consumo médio de proteína/kg de peso, calorias, fósforo e Potássio, com diferença significativa da ingestão média de proteína/kg (p = 0,04) e fósforo (p = 0,045). O tempo em HD alterou a composição corporal dos pacientes, indicando um declínio doestado nutricional desses indivíduos. Conclusão: Pacientes com HD são um grupo de risco para desnutrição protéico-energética, onde o tempo em HD interfere no perfil antropométrico e alimentar do paciente.O grupo com tempo de HD superior ou igual a 3 anos apresentou piora do estado nutricional.

Gut microbiota imbalance is common in patients with chronic kidney disease (CKD) and associates with factors such as increased circulating levels of gut-derived uremic toxins, inflammation, and oxidative stress, which are linked to cardiovascular disease and increased morbimortality. Different nutritional strategies have been proposed to modulate gut microbiota, and could potentially be used to reduce dysbiosis in CKD. Nutrients like proteins, fibers, probiotics, and synbiotics are important determinants of the composition of gut microbiota and specific bioactive compounds such as polyphenols present in nuts, berries. and fruits, and curcumin, may also play a key role in this regard. However, so far, there are few studies on dietary components influencing the gut microbiota in CKD, and it is therefore not possible to conclude which nutrients should be prioritized in the diet of patients with CKD. In this review, we discuss some nutrients, diet patterns and bioactive compounds that may be involved in the modulation of gut microbiota in CKD and provide the background and rationale for studies exploring whether nutritional interventions with these dietary components could be used to alleviate the gut dysbiosis in patients with CKD.