Effect of Unripe Banana Flour on Gut-Derived Uremic Toxins in Individuals Undergoing Peritoneal Dialysis: A Randomized, Double-Blind, Placebo-Controlled, Crossover Trial.

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.

Influence of bowel habits on gut-derived toxins in peritoneal dialysis patients.

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.