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PURPOSE OF REVIEW: This narrative review aimed to summarize the current evidence on the connection between dysbiosis and vitamin K deficiency in patients with chronic kidney disease (CKD). The presence of dysbiosis (perturbations in the composition of the microbiota) has been described in several non-communicable diseases, including chronic kidney disease, and it has been hypothesized that dysbiosis may cause vitamin K deficiency. Patients with CKD present both vitamin K deficiency and gut dysbiosis; however, the relationship between gut dysbiosis and vitamin K deficiency remains to be addressed. RECENT FINDINGS: Recently, few studies in animals have demonstrated that a dysbiotic environment is associated with low production of vitamin K by the gut microbiota. Vitamin K plays a vital role in blood coagulation as well as in the cardiovascular and bone systems. It serves as a cofactor for γ-glutamyl carboxylases and thus is essential for the post-translational modification and activation of vitamin K-dependent calcification regulators, such as osteocalcin, matrix Gla protein, Gla-rich protein, and proteins C and S. Additionally, vitamin K executes essential antioxidant and anti-inflammatory functions. Dietary intake is the main source of vitamin K; however, it also can be produced by gut microbiota. This review discusses the effects of uremia on the imbalance in gut microbiota, vitamin K-producing bacteria, and vitamin K deficiency in CKD patients, leading to a better understanding and raising hypothesis for future clinical studies.

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.

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.

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.