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AbstractPurpose: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.Methods: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.Results: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.Conclusion: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 .

Oxidative stress and inflammation are common findings in chronic kidney disease (CKD) patients, and they are directly linked to clinical outcomes such as protein energy wasting and cardiovascular disease. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is the master regulator of antioxidant genes, regulating the expression of detoxifying enzymes of phase II and antioxidant responses. Furthermore, Nrf2 can also regulate anti-inflammatory cellular responses, by inhibiting nuclear factor kappa B activity (transcription factor that promotes inflammation). Therefore, modulating Nrf2 can be a new therapeutic approach to reduce inflammation and oxidative stress in CKD. Low-protein diet (LPD) prescribed for nondialysis CKD patients presents numerous benefits already well established, including reduction of inflammation and oxidative stress. However, there is no available data regarding the relationship between LPD and Nrf2 modulation in these patients. This review aims to discuss the impact, if any, of LPD on Nrf2 expression, in nondialysis CKD patients.

Under physiologic conditions, the human gut microbiota performs several activities essential to the body health. In contrast, their imbalances exacerbate some actions which can promote a cascade of metabolic abnormalities, and vice versa. Numerous diseases, including chronic kidney disease, are associated with gut microbiota imbalance, and among several strategies to re-establish gut symbiosis, prebiotics seem to represent an effective nonpharmacological approach. Prebiotics fermentation by gut microbiota produce short-chain fatty acids, which improve the gut barrier integrity and function, and modulate the glucose and lipid metabolism as well as the inflammatory response and immune system. Therefore, this literature review intends to discuss the beneficial effects of prebiotics in human health through short-chain fatty acids production, with a particular interest on chronic kidney disease.

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.

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