In chronic kidney disease (CKD), the accumulation of gut-derived metabolites, such as indoxyl sulfate (IS), p-cresyl sulfate (pCS), and indole 3-acetic acid (IAA), has been associated with the burden of the disease. In this context, prebiotics emerge as a strategy to mitigate the accumulation of such compounds, by modulating the gut microbiota and production of their metabolites. The aim of this study was to evaluate the effect of unripe banana flour (UBF—48% resistant starch, a prebiotic) on serum concentrations of IS, pCS, and IAA in individuals undergoing peritoneal dialysis (PD). A randomized, double-blind, placebo-controlled, crossover trial was conducted. Forty-three individuals on PD were randomized to sequential treatment with UBF (21 g/day) and placebo (waxy corn starch—12 g/day) for 4 weeks, or vice versa (4-week washout). The primary outcomes were total and free serum levels of IS, pCS, and IAA. Secondary outcomes were 24 h urine excretion and dialysis removal of IS, pCS, and IAA, serum inflammatory markers [high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α)], serum lipopolysaccharide LPS, and dietary intake. Of the 43 individuals randomized, 26 completed the follow-up (age = 55 ± 12 years; 53.8% men). UBF did not promote changes in serum levels of IS (p = 0.70), pCS (p = 0.70), and IAA (p = 0.74). Total serum IS reduction was observed in a subgroup of participants (n = 11; placebo: median 79.5 μmol/L (31–142) versus UBF: 62.5 μmol/L (31–133), p = 0.009) who had a daily UBF intake closer to that proposed in the study. No changes were observed in other secondary outcomes. UBF did not promote changes in serum levels of IS or pCS and IAA; a decrease in IS was only found in the subgroup of participants who were able to take 21g/day of the UBF.

Endothelial microparticles (EMPs) are vesicles derived from cell membranes, which contain outsourced phosphatidylserine and express adhesion molecules, such as cadherin, intercellular cell adhesion molecule-1 (ICAM-1), E-selectin, and integrins. EMPs are expressed under physiological conditions and continue circulating in the plasma. However, in pathologic conditions their levels increase, and they assume a pro-inflammatory and pro-coagulant role via interactions with monocytes; these effects are related to the development of atherosclerosis. Chronic kidney dysfunction (CKD) characterizes this dysfunctional scenario through the accumulation of uremic solutes in the circulating plasma, whose toxicity is related to the development of cardiovascular diseases. Therefore, this review aims to discuss the formation of EMPs and their biological effects in the uremic environment. Data from previous research demonstrate that uremic toxins are closely associated with the activation of inflammatory biomarkers, cardiovascular dysfunction processes, and the release of EMPs. The impact of a decrease in circulating EMPs in clinical studies has not yet been evaluated. Thus, whether MPs are biochemical markers and/or therapeutic targets has yet to be established.

Chronic kidney disease (CKD) is characterized by loss of renal function and a consequent increase of serum uremic toxins, which contribute to inflammation status. Deficiency of 25-vitamin D, often found in patients with CKD, has been included as an inflammatory factor since it might modulate the immune system. The aim of this study was to investigate the role of 25-vitamin D on inflammatory pathways in healthy and uremic environment. Toll-like receptor 4 (TLR4), oxidative stress (ROS), vitamin D receptor (VDR), 1-α hydroxylase (CYP27), 24 hydroxylase, cathelicidin, and MCP-1 were evaluated in monocytes exposed to a uremic serum pool compared with healthy pool. The human monocytes lineage (U937) was incubated with or without 25-vitamin D (50 ng/ml for 24 hours). TRL4, VDR, CYP27, CYP24, and ROS were evaluated by flow cytometry. We used ELISA to measure IL-6, TNF-α, IL-10, cathelicidin, and MCP-1 in the cell culture supernatant. We observed a higher expression of TRL-4, IL-6, TNF-α, IL-10, cathelicidin and MCP-1 in monocytes incubated with uremic serum when compared with serum from healthy individuals. Supplementation of 25-vitamin D was able to reduce the expression of TRL4, cathelicidin, and MCP-1 in the uremic environment. There was no difference in the expression of VDR, CYP27 and CYP24 intracellular enzymes. This in vitro study showed that the uremic pool activates inflammatory response in monocytes, which was reversed by 25-vitamin D supplementation; this finding suggests that 25-vitamin D has an anti-inflammatory role in the uremic environment.

Background Gut-derived uremic toxins have been associated with adverse outcomes in chronic kidney disease (CKD). Alterations in bowel habits, including constipation, seem to play an additional role in uremic toxicity. The aim of this study is to investigate the association of bowel habits with gut-derived uremic toxins and intestinal permeability in patients on automated peritoneal dialysis (APD). Methods This cross-sectional study enrolled 58 APD patients (age 52.5 ± 15.1 years; dialysis vintage 14.1 (6.0–36.5) months). Constipation was defined according to the Rome IV criteria. Bowel habits were assessed by the Bristol Stool Scale (BSS < 3 characterized by hard consistency of stools and/or low frequency of evacuation, a surrogate of slow intestinal transit time, and BSS ≥ 3, defining regular bowel habit). The total and free serum concentration of p-cresyl sulfate (PCS), indoxyl sulfate (IS) and indole-3-acetic acid (IAA) were dosed by high-performance liquid chromatography. Lipopolysaccharide (LPS) and zonulin were assessed by ELISA and d(–)-lactate by colorimetric method. Dietary intake was assessed by the 3-day food records. Results No differences were observed in clinical, demographic, and dietary characteristics between constipated (n = 30) and non-constipated (n = 28) groups. A trend for higher total PCS (p = 0.07) and free PCS (p = 0.06) was found in constipated patients. Patients with BSS < 3 (n = 11) exhibited significantly higher levels of total and free PCS (p < 0.01) and total IAA (p = 0.04). Conversely, No difference was found in IS levels. Except for a lower serum level of d(–)-lactate in patients with BSS < 3 (p = 0.01), zonulin and LPS levels were not different. Conclusions Disturbed bowel habits, mainly characterized by slow transit time, may play a role in the accumulation of uremic toxins, particularly PCS, in patients on automatized peritoneal dialysis.