Sulforaphane Supplementation Did Not Modulate NRF2 and NF-kB mRNA Expressions in Hemodialysis Patients.

BACKGROUND: Patients with chronic kidney disease (CKD) have reduced expression of erythroid nuclear factor-related factor 2 (NRF2) and increased nuclear factor κB (NF-κB). "Food as medicine" has been proposed as an adjuvant therapeutic alternative in modulating these factors. No studies have investigated the effects of sulforaphane (SFN) in cruciferous vegetables on the expression of these genes in patients with CKD. OBJECTIVE: The study aimed to evaluate the effects of SFN on the expression of NRF2 and NF-κB in patients on hemodialysis (HD). DESIGN AND METHODS: A randomized, double-blind, crossover study was performed on 30 patients on regular HD. Fourteen patients were randomly allocated to the intervention group (1 sachet/day of 2.5 g containing 1% SFN extract with 0.5% myrosinase) and 16 patients to the placebo group (1 sachet/day of 2.5 g containing corn starch colored with chlorophyll) for 2 months. After a washout period of 2 months, the groups were switched. NRF2 and NF-κB mRNA expression was evaluated by real-time quantitative polymerase chain reaction, and tumor necrosis factor alpha and interleukin-6 levels were quantified by enzyme-linked immunosorbent assay. Malondialdehyde was evaluated as a marker of lipid peroxidation. RESULTS: Twenty-five patients (17 women, 55 [interquartile range = 19] years and 55 [interquartile range = 74] months on HD) completed the study. There was no significant difference concerning the expression of mRNA NRF2 (P = .915) and mRNA NF-κB (P = .806) after supplementation with SFN. There was no difference in pro-inflammatory and oxidative stress biomarkers. CONCLUSION: 150 µmol of SFN for 2 months had no antioxidant and anti-inflammatory effect in patients with CKD undergoing HD.

Blueberry, cranberry, raspberry, and strawberry as modulators of the gut microbiota: target for treatment of gut dysbiosis in chronic kidney disease? From current evidence to future possibilities.

Gut dysbiosis is common in patients with chronic kidney disease (CKD) and is associated with uremic toxin production, inflammation, oxidative stress, and cardiovascular disease development. Therefore, healthy dietary patterns are essential modulators of gut microbiota. In this context, studies suggest that consuming berry fruits, rich in polyphenols and nutrients, may positively affect the gut microbiota, promoting the selective growth of beneficial bacteria and improving clinical status. However, studies on the effects of berry fruits on gut microbiota in CKD are scarce, and a better understanding of the possible mechanisms of action of berry fruits on gut microbiota is needed to guide future clinical studies and clinical practice in CKD. The objective was to discuss how berry fruits (blueberry, cranberry, raspberry, and strawberry) could be a therapeutic strategy to modulate the gut microbiota and possibly reverse the dysbiosis in CKD. Overall, available evidence shows that berry fruits can promote an increase in diversity by affecting the abundance of mucus-producing bacteria and short-chain fatty acids. Moreover, these fruits can increase the expression of mRNA involved in tight junctions in the gut such as occludin, tight junction protein 1 (TJP1), and mucin. Studies on the exact amount of berries leading to these effects show heterogeneous findings. However, it is known that, with 5 mg/day, it is already possible to observe some effects in animal models. Wild berries could possibly improve the uremic condition by reducing the levels of uremic toxins via modulation of the gut microbiota. In the long term, this could be an excellent strategy for patients with CKD. Therefore, clinical studies are encouraged to evaluate better these effects on CKD as well as the safe amount of these fruits in order to promote a better quality of life or even the survival of these patients.

Is Trimethylamine N-oxide (TMAO) Associated with NF-κB mRNA Expression in Patients with Coronary Artery Disease?

Abstract Background: Trimethylamine N-oxide (TMAO), a gut microbiota metabolite, is associated with cardiovascular disease (CVD) development. TMAO can trigger an inflammatory response by inducing the nuclear factor-kappa B (NF-κB) signaling cascade and increasing the expression of pro-inflammatory cytokines, contributing to the worsening of CVD. This study aimed to evaluate the association between TMAO plasma levels and inflammation in patients with coronary artery disease (CAD). Methods: A cross-sectional study was carried out including 29 patients with CAD. Peripheral blood mononuclear cells (PBMC) were isolated from fasting blood samples, and NF-κB and vascular cell adhesion protein 1 (VCAM1) mRNA expression were estimated using real-time quantitative PCR. We determined TMAO plasma levels by LC-MS/MS and TNF-α by ELISA. Routine biochemical parameters were evaluated using an automatic biochemical analyzer. Correlations were estimated by Spearman or Pearson test. Statistical significance was set at the level of p < 0.05. Results: All patients presented TMAO levels within the normal range according to EUTox (normal range: 2.83 ± 1.53 mg/L; CAD patients: 0.2 [0.1 to 0.2] ng/μL). TMAO plasma levels were positively correlated with NF-κB mRNA expression (0.555; p = 0.002). Conclusion: TMAO plasma levels may be associated with NF-κB mRNA expression in patients with CAD and may contribute to the pathogenesis of this disease.

Protect the Kidneys and Save the Heart Using the Concept of Food as Medicine.

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.

Effects of Polydextrose Supplementation on Intestinal Function in Hemodialysis Patients: A Double-Blind, Randomized, Placebo-Controlled Trial.

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.

Effects of resveratrol on inflammation and oxidative stress induced by the uremic toxin indoxyl sulfate in Murine macrophage-like RAW 264.7.

Indoxyl sulfate (IS) is a uremic toxin produced by the gut microbiota that commonly accumulates in patients with chronic kidney disease (CKD) and can be harmful. Resveratrol is a polyphenol with properties that attenuate oxidative stress and inflammation. This study aims to evaluate the effect of resveratrol against the damage caused by IS in RAW 264.7 murine macrophages. Cells were treated with 0, 250, 500 and 1000 µmol/L of IS, in the presence of 50 µmol/L of resveratrol. The mRNA and protein expressions of erythroid-related nuclear factor 2 (Nrf2) and nuclear factor kappa-B (NF-κB) were measured using rt-PCR and Western blot analysis, respectively. Malondialdehyde (MDA) and reactive oxygen species (ROS) levels were also analyzed. As a result, it was demonstrated that resveratrol induces the activation of the Nrf2 pathway that enhances cytoprotective response. IS upregulated the NF-κB expression and downregulated the Nrf2 expression. In contrast, resveratrol treatment significantly reduced the MDA and ROS production and inhibited the IS-induced expression of NF-κB in macrophage-like RAW 264.7. In conclusion, resveratrol can mitigate inflammation and oxidative stress caused by uremic toxins produced by the gut microbiota, such as IS.

The effect of Brazilian Green Propolis extract on inflammation in patients with chronic kidney disease on peritoneal dialysis: A randomised double-blind controlled clinical trial.

BACKGROUND: Chronic kidney disease (CKD) patients on dialysis display a low-grade systemic inflammatory burden. Nutritional interventions designed to activate the cytoprotective nuclear factor erythroid-2-related factor 2 (Nrf2) and inhibit nuclear factor-kB (NF-κB) have been proposed to mitigate this burden. Several bioactive compounds have been investigated to achieve this, including propolis, a resin produced by Apis mellifera bees. Considering the safety and efficacy of propolis, it could be a strategy to benefit these patients. Still, there are no studies using propolis in patients with CKD on peritoneal dialysis (DP), and clinical studies to support this application are lacking. HYPOTHESIS/PURPOSE: The objective and novelty of the present study are to evaluate the effects of propolis supplementation on inflammatory markers in patients with CKD on PD. STUDY DESIGN: A longitudinal, double-blind, placebo-controlled trial with CKD patients on PD. METHODS: The patients were randomised into two groups: propolis that received four capsules of 100 mg (400 mg/day), containing concentrated and standardised dry EPP-AF® Brazilian green propolis extract) or placebo, four capsules of 100 mg (400 mg/day), of magnesium stearate, silicon dioxide, and microcrystalline cellulose, for two months. Plasma levels of inflammatory cytokines, including tumour necrosis factor (TNF-α) and interleukin-6 (IL-6), were evaluated by ELISA. Quantitative real-time PCR analyses were performed to evaluate the transcriptional expression levels of Nrf2 and NF-κB in peripheral blood mononuclear cells (PBMCs). Plasma malondialdehyde (MDA) levels, a lipid peroxidation marker, was measured as thiobarbituric acid reactive substances (TBARS). Routine biochemical markers, including C-reactive protein (CRP), were analysed using commercial kits. Carotid Intima-Media Thickness (CIMT) was measured with a doppler ultrasonography device. The study was registered on ClinicalTrials.gov under the number NCT04411758. RESULTS: A total of 19 patients completed the study, ten patients in the propolis group (54 ± 1.0 years, five men, 7.2  (5.1) months on PD) and 9 in the placebo group (47.5 ± 15.2 years, three men, 10.8  (24.3) months on PD). The plasma levels of TNF-α reduced significantly (p = 0.02), and expression of Nrf2 showed a trend to increase (p = 0.07) after propolis supplementation. CONCLUSION: EPP-AF® Green Propolis extract (400 mg/day) supplementation for two months appears as a potential strategy to mitigate inflammation, reducing TNF-α plasma levels in CKD patients on PD.

Effects of propolis on inflammation markers in patients undergoing hemodialysis: A randomized, double-blind controlled clinical trial.

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/m2) and 20 in the placebo group (45.5 ± 14 years, 13 women, BMI, 24.8 ± 6.8 kg/m2). 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-1ß (MIP-1ß) (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-1ß in patients with CKD on HD. This study was registered at clinicaltrials.gov (NCT04411758).

Dark chocolate (70% cocoa) attenuates the inflammatory marker TNF-α in patients on hemodialysis.

BACKGROUND: Inflammation and oxidative stress lead to a high risk of cardiovascular disease in patients with chronic kidney disease (CKD). Food rich in polyphenols such as dark chocolate may be an effective strategy to mitigate inflammation and delay CKD complications, outwith sensorial pleasure promotion. The aim of this study was to evaluate the effects of dark chocolate on inflammation and oxidative stress markers in patients with CKD on hemodialysis (HD). METHODS: A clinical trial was carried out with 59 patients who were allocated into the chocolate group [40g of dark chocolate (70% cocoa) offered during HD sessions, 3×/week] or the control group with any intervention for two months. Plasma levels of the inflammatory cytokines TNF-α and IL-6 were evaluated by the ELISA method. Thiobarbituric acid reactive substances such as malondialdehyde (MDA) and LDLox levels were evaluated as lipid peroxidation markers. Routine biochemical parameters were analysed using commercial BioClin® kits. RESULTS: Thirty-five patients completed the chocolate group (18 men, 53.0 (16) years and 31.0 (39) months on HD) and 11 in the control group (7 men, 48.0 (17.5) years and 44.0 (56.5) months on HD). Regarding the differences between the groups, the patients who received dark chocolate had reduced plasma levels of TNF-α compared to the control (p = 0.008). No significant changes were observed in the oxidative stress parameters evaluated in both groups. Routine biochemical (including phosphorus and potassium levels) and anthropometric parameters and food intake were not changed after the study period. CONCLUSION: The intervention with dark chocolate (70% cocoa) for two months reduced the plasma levels of TNF-α in patients with CKD on HD. In addition, it is essential to emphasise that chocolate intake did not increase the plasma levels of phosphorus and potassium in these patients. This study was registered at clinicaltrials.gov as NCT04600258.

Consumo de Castanha-do-Brasil reduz o N-óxido de trimetilamina (TMAO) e a inflamação em um paciente com síndrome cardiorrenal: uma comunicação breve / Brazil nut consumption reduces trimethylamine-n-oxide (TMAO) and inflammation in a patient with cardiorenal syndrome: a brief communication

Introdução: A disbiose intestinal é uma característica comum na síndrome cardiorrenal e está associada ao aumento de toxinas urêmicas, como o N-óxido de trimetilamina (TMAO), que estão envolvidas com a inflamação e mortalidade cardiovascular. A castanha-do-Brasil (semente típica brasileira) possui propriedades anti-inflamatórias e antioxidantes, mas não há evidências dos seus efeitos na modulação da microbiota intestinal e redução de toxinas urêmicas. Objetivo: Avaliar o impacto do consumo de castanha-do-Brasil nos níveis de TMAO e marcadores de inflamação em um paciente com síndrome cardiorrenal. Métodos: Um paciente com doença arterial coronariana (66 anos e IMC, 26 kg/m2), estágio 3 da DRC (TFGe 36 mL/min), recebeu uma castanha-do-Brasil por dia durante três meses. Resultados: Os níveis plasmáticos de TMAO e a expressão de mRNA de NF-κB foram reduzidos e a atividade da glutationa peroxidase (GPx) aumentou após esta intervenção. Conclusão: A prescrição de castanha-do-Brasil pode ser uma estratégia promissora para mitigar as complicações relacionadas à síndrome cardiorrenal. Este caso apoia o conceito de "alimento como remédio" visando o fenótipo urêmico na síndrome cardiorrenal.

Introduction: Gut dysbiosis is a common feature in cardiorenal syndrome, and it is linked to increased uremic toxins, like trimethylamine-n-oxide (TMAO), which are involved with inflammation and cardiovascular mortality. Brazil nut (typical Brazilian seed) has anti-inflammatory and antioxidant properties, but there is no evidence of the effects of gut microbiota modulation and reduction of uremic toxins. Objective: To assess the impact of Brazil nut consumption on TMAO levels and inflammation markers in a patient with cardiorenal syndrome. Methods: Acoronary artery disease patient(66 years and BMI, 26 kg/m2),stage-3 of CKD (eGFR 36 mL/min), receivedone Brazil nut per day for three months. Results: TMAO plasma levels and NF-κB mRNA expression were reduced, and glutathione peroxidase (GPx) activity increased after this intervention. Conclusion: Brazil nut prescription may be a promising strategy to mitigate complications related tothe cardiorenal syndrome. This case supports the concept of "Food as medicine" targeting the uremic phenotype in cardiorenal syndrome.

Bioactive compounds modulating Toll-like 4 receptor (TLR4)-mediated inflammation: pathways involved and future perspectives.

Chronic inflammation is associated with the development and progression of several noncommunicable diseases, such as diabetes, cardiovascular disease, chronic kidney disease, cancer, and nonalcoholic fatty liver disease. Evidence suggests that pattern recognition receptors that identify pathogen-associated molecular patterns and danger-associated molecular patterns are crucial in chronic inflammation. Among the pattern recognition receptors, Toll-like receptor 4 (TLR4) stimulates several inflammatory pathway agonists, such as nuclear factor-κB, interferon regulator factor 3, and nod-like receptor pyrin domain containing 3 pathways, which consequently trigger the expression of pro-inflammatory biomarkers, increasing the risk of noncommunicable disease development and progression. Studies have focused on the antagonistic potential of bioactive compounds, following the concept of food as a medicine, in which nutritional strategies may mitigate inflammation via TLR4 modulation. Thus, this review discusses preclinical evidence concerning bioactive compounds from fruit, vegetable, spice, and herb extracts (curcumin, resveratrol, catechin, cinnamaldehyde, emodin, ginsenosides, quercetin, allicin, and caffeine) that may regulate the TLR4 pathway and reduce the inflammatory response. Bioactive compounds can inhibit TLR4-mediated inflammation through gut microbiota modulation, improvement of intestinal permeability, inhibition of lipopolysaccharide-TLR4 binding, and decreasing TLR4 expression by modulation of microRNAs and antioxidant pathways. The responses directly mitigated inflammation, especially nuclear factor-κB activation and inflammatory cytokines release. These findings should be considered for further clinical studies on inflammation-mediated diseases.

The Role of Betaine in Patients With Chronic Kidney Disease: a Narrative Review.

PURPOSE OF REVIEW: This narrative review aimed to explore the functions of betaine and discuss its role in patients with chronic kidney disease (CKD). RECENT FINDINGS: 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.

Consumption of oils and anthocyanins may positively modulate PPAR-γ expression in chronic noncommunicable diseases: A systematic review.

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.

Resistant Starch Type-2 Supplementation Does Not Decrease Trimethylamine N-Oxide (TMAO) Plasma Level in Hemodialysis Patients.

Dysbiosis is recognized as a new cardiovascular disease (CVD) risk factor in hemodialysis (HD) patients because it is linked to increased generation in the gut of uremic toxins such as trimethylamine N-Oxide (TMAO) from dietary precursors (choline, betaine, or L-carnitine). Nutritional strategies have been proposed to modulate the gut microbiota and reduce the production of these toxins. This study aimed to evaluate the effect of amylose-resistant starch (RS) supplementation on TMAO plasma levels in HD patients.We conducted a randomized, double-blind, placebo-controlled trial (NCT02706808) with patients undergoing HD enrolled in a previous pilot study. The participants were allocated to RS or placebo groups to receive 16 g/d of RS or placebo for 4 weeks. Plasma TMAO, choline, and betaine levels were measured with LC-MS/MS. Fecal microbiome composition was evaluated by 16S ribosomal RNA sequencing, followed by a search for TMA-associated taxa. Anthropometric, routine biochemical parameters, and food intake were evaluated.Twenty-five participants finished the study, 13 in the RS group, and 12 in the placebo group. RS supplementation did not reduce TMAO plasma levels. Moreover, no significant alterations were observed in choline, betaine, anthropometric, biochemical parameters, or food intake in both groups. Likewise, RS was not found to exert any influence on the proportion of potential TMA-producing bacterial taxa in fecal matter.RS supplementation did not influence plasma TMAO, choline, betaine, or fecal taxa potentially linked to TMAO. Thus, RS does not seem to modify the TMA-associated bacterial taxa, precursors of TMAO.Supplemental data for this article is available online at https://doi.org/10.1080/07315724.2021.1967814 .

Curcumin supplementation improves oxidative stress and inflammation biomarkers in patients undergoing hemodialysis: a secondary analysis of a randomized controlled trial.

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.

Inhibiting BTB domain and CNC homolog 1 (Bach1) as an alternative to increase Nrf2 activation in chronic diseases.

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.

Can Resveratrol Supplementation Reduce Uremic Toxin Plasma Levels From the Gut Microbiota in Nondialyzed Patients With Chronic Kidney Disease?

OBJECTIVES: 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. METHODS: 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/m2) or a placebo containing 500 mg wheat flour (62 ± 8.4 years, GFR: 34 ± 13 mL/min, body mass index: 28.6 ± 4.4 kg/m2) during 4 weeks. After 8 weeks of washout (no supplementation), another 4 weeks of supplementation with crossover was initiated. IS, IAA, and pCS plasma levels were quantified by the reverse phase high-efficiency liquid chromatography method with fluorescent detection. The mRNA expression of nuclear factor erythroid 2-related factor 2 and nuclear factor kappa B in peripheral blood mononuclear cells was evaluated by polymerase chain reaction. C-reactive protein plasma levels were also evaluated. RESULTS: As 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). CONCLUSION: 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.

Effect of cranberry supplementation on toxins produced by the gut microbiota in chronic kidney disease patients: A pilot randomized placebo-controlled trial.

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.

Oral iron supplementation in patients with chronic kidney disease: Can it be harmful to the gut microbiota?

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.

From the distinctive smell to therapeutic effects: Garlic for cardiovascular, hepatic, gut, diabetes and chronic kidney disease.

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.