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Effect of increasing dietary fiber on plasma levels of colon-derived solutes in hemodialysis patients.

ABSTRACT: Numerous uremic solutes are derived from the action of colon microbes. Two such solutes, indoxyl sulfate and p-cresol sulfate, have been associated with adverse outcomes in renal failure. This study tested whether increasing dietary fiber in the form of resistant starch would lower the plasma levels of these solutes in patients on hemodialysis.Fifty-six patients on maintenance hemodialysis were randomly assigned to receive supplements containing resistant starch (n=28) or control starch (n=28) daily for 6 weeks in a study conducted between October 2010 and May 2013. Of these, 40 patients (20 in each group) completed the study and were included in the final analysis. Plasma indoxyl sulfate and p-cresol sulfate levels were measured at baseline and week 6.Increasing dietary fiber for 6 weeks significantly reduced the unbound, free plasma level of indoxyl sulfate (median -29% [25th percentile, 75th percentile, -56, -12] for fiber versus -0.4% [-20, 34] for control, P=0.02). The reduction in free plasma levels of indoxyl sulfate was accompanied by a reduction in free plasma levels of p-cresol sulfate (r=0.81, P<0.001). However, the reduction of p-cresol sulfate levels was of lesser magnitude and did not achieve significance (median -28% [-46, 5] for fiber versus 4% [-28, 36] for control, P=0.05).Increasing dietary fiber in hemodialysis patients may reduce the plasma levels of the colon-derived solutes indoxyl sulfate and possibly p-cresol sulfate without the need to intensify dialysis treatments. Further studies are required to determine whether such reduction provides clinical benefits.

SUBMITTER: Sirich TL

PROVIDER: S-EPMC4152802 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Effect of increasing dietary fiber on plasma levels of colon-derived solutes in hemodialysis patients.

Sirich Tammy L TL Plummer Natalie S NS Gardner Christopher D CD Hostetter Thomas H TH Meyer Timothy W TW

Clinical journal of the American Society of Nephrology : CJASN 20140821 9

<h4>Background and objectives</h4>Numerous uremic solutes are derived from the action of colon microbes. Two such solutes, indoxyl sulfate and p-cresol sulfate, have been associated with adverse outcomes in renal failure. This study tested whether increasing dietary fiber in the form of resistant starch would lower the plasma levels of these solutes in patients on hemodialysis.<h4>Design, setting, participants, & measurements</h4>Fifty-six patients on maintenance hemodialysis were randomly assig ...[more]

PMID: 25147155

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Project description:BACKGROUND:There is growing evidence that the accumulation of protein- bound uremic retention solutes, such as indoxyl sulfate, p-cresyl sulfate and kynurenic acid, play a role in the accelerated cardiovascular disease seen in patients undergoing chronic hemodialysis. Protein-binding, presumably to albumin, renders these solutes poor-dialyzable. We previously observed that the free fraction of indoxyl sulfate was markedly reduced at the end of hemodialysis. We hypothesized that solute binding might be pH-dependent and attributed the changes in free solute concentration to the higher serum pH observed at the end of standard hemodialysis with dialysis buffer bicarbonate concentration greater than 35 mmol/L. We observed that acidification of uremic plasma to pH 6 in vitro greatly increased the proportion of freeIS. METHODS:We tested our hypothesis by reducing the dialysate bicarbonate buffer concentration to 25 mmol/L for the initial half of the hemodialysis treatment ("isohydric dialysis"). Eight stable hemodialysis patients underwent "isohydric dialysis" for 90 minutes and then were switched to standard buffer (bicarbonate = 37mmol/L). A second dialysis, 2 days later, employed standard buffer throughout. RESULTS:We found a clearcut separation of blood pH and bicarbonate concentrations after 90 minutes of "isohydric dialysis" (pH = 7.37, bicarbonate = 22.4 mmol/L) and standard dialysis (pH = 7.49, bicarbonate = 29.0 mmol/L). Binding affinity varied widely among the 10 uremic retention solutes analyzed. Kynurenic acid (0.05 free), p-cresyl sulfate (0.12 free) and indoxyl sulfate (0.13 free) demonstrated the greatest degree of binding. Three solutes (indoxyl glucuronide, p-cresyl glucuronide, and phenyl glucuronide) were virtually unbound. Analysis of free and bound concentrations of uremic retention solutes confirmed our prediction that binding of solute is affected by pH. However, in a mixed models analysis, we found that the reduction in total uremic solute concentration during dialysis accounted for a greater proportion of the variation in free concentration, presumably an effect of saturation binding to albumin, than did the relatively small change in pH produced by isohydric dialysis. The effect of pH on binding appeared to be restricted to those solutes most highly protein-bound. The solutes most tightly bound exhibited the lowest dialyzer clearances. An increase in dialyzer clearance during isohydric and standard dialyses was statistically significant only for kynurenic acid. CONCLUSION:These findings provide evidence that the binding of uremic retention solutes is influenced by pH. The effect of reducing buffer bicarbonate concentration ("isohydric dialysis:"), though significant, was small but may be taken to suggest that further modification of dialysis technique that would expose blood to a greater decrease in pH would lead to a greater increase the free fraction of solute and enhance the efficacy of hemodialysis in the removal of highly protein-bound uremic retention solutes.

Project description:This study investigated the influence of dietary fiber levels on the growth performance, digestion, metabolism, and cecal microbial community of rabbits with different diets at different age. The different levels of dietary natural detergent fiber (NDF) were formulated accordingly: 400(A), 350(B), 300(C), 250(D) g/kg original matter basis, respectively; the different ages were 52, 62, and 72 days. With NDF increasing, the average daily feed intake (ADFI) and feed conversion rate (FCR) were increased, whereas average daily gain (ADG) and mortality were decreased (p < 0.05). The stomach relative weight, stomach content relative weight, cecal relative weight, and cecal content weight increased with increasing NDF (p < 0.05). The NH3 -N concentration of cecum dropped when the dietary NDF increased (p < 0.05). The diversity of the total microbiota increased significantly in Diets B, C (p = 0.011), and reached the lowest in 52 days for all diet groups. The richness index was decreased significantly in Diet A, D (p < 0.05) and in 62 days (p < 0.001), respectively. The phylum Firmicutes was higher (p < 0.01) in rabbits fed Diets B, C than Diets A, D and Bacteroidetes was highest in Diets C, D, and Proteobacteria was the highest in Diet A (p < 0.001). Among the classified genera, there were 14 that had levels of abundance of more than 1% and were commonly shared by all samples. Ruminococcus spp. that produced volatile fatty acid (VFA) abundance was highest from Diets B, C at 52 and 62 days. It is interesting to note that Bifidobacterium from Diet C was the most abundant genus during the entire experimental period (p < 0.01). The data from Venn diagrams, principal component analysis (PCA), and heat map plots of the bacterial communities showed that there were more groups of shared microbiota with aging. The above results indicate the cecal microbiota controlled by the 350 g/kg NDF diet can prevent gastrointestinal distress and exhibit good production performance.

Dataset Information

Effect of increasing dietary fiber on plasma levels of colon-derived solutes in hemodialysis patients.

Publications

Effect of increasing dietary fiber on plasma levels of colon-derived solutes in hemodialysis patients.

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