Effect of increasing dietary fiber on plasma levels of colon-derived solutes in hemodialysis patients.
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ABSTRACT:
SUBMITTER: Sirich TL
PROVIDER: S-EPMC4152802 | biostudies-literature | 2014 Sep
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND AND OBJECTIVES:Colon microbial metabolism produces solutes that are normally excreted in the urine and accumulate in the plasma when the kidneys fail. This study sought to further identify and characterize human colon-derived uremic solutes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:Colon-derived solutes normally excreted in the urine were identified by comparing urine from controls (n=17) and patients with total colectomies (n=12), using an established metabolomic platform. Colon-derived solutes that accumulate in kidney failure were then identified by comparing the plasma of the control patients with that of patients on dialysis (n=14). RESULTS:Ninety-one urinary solutes were classified as colon-derived on the basis of the finding of a urine excretion rate at least four-fold higher in control patients than in patients with total colectomies. Forty-six were solutes with known chemical structure, 35 of which had not previously been identified as colon-derived. Sixty of the colon-derived solutes accumulated in the plasma of patients with ESKD to a degree greater than urea and were therefore classified as uremic. The estimated urinary clearance for 27 out of the 32 colon-derived solutes for which clearance could be calculated exceeded that of creatinine, consistent with tubular secretion. Sulfatase treatment revealed that 42 out of the 91 colon-derived solutes detected were likely conjugates. CONCLUSIONS:Metabolomic analysis identified numerous colon-derived solutes that are normally excreted in human urine. Clearance by tubular secretion limits plasma levels of many colon-derived solutes.
| S-EPMC6140561 | biostudies-other
Project description:IntroductionDeclining renal function results in the accumulation of solutes normally excreted by healthy kidneys. Data suggest that some of the protein-bound solutes mediate accelerated cardiovascular disease. Many of the poorly dialyzable protein-bound uremic retention solutes are products of gut bacterial metabolism.MethodsWe performed a blinded-randomized controlled trial comparing the changes in plasma concentrations of a panel of protein-bound solutes and microbiome structure in response to the once-weekly oral administration of 250 mg of vancomycin or placebo over a period of 12 weeks in a cohort of stable patients with end-stage kidney disease. We also examined the pattern of recovery of the solutes and gut microbiome over 12 weeks of placebo administration following vancomycin.ResultsWe enrolled 15 subjects. Ten subjects provided sufficient plasma and stool samples to permit us to examine the effect of vancomycin on plasma solute levels. We showed that a weekly dose of vancomycin resulted in a reduction in the plasma concentration of 7 colon-derived solutes. We described a significant effect of vancomycin on the microbiome structure with a decrease in alpha diversity and change in beta diversity. Multiple taxa decreased with vancomycin including genera Clostridium and Bacteroides. We demonstrated microbiome recovery after stopping vancomycin. However, recovery in the solutes was highly variable between subjects.ConclusionsWe demonstrated that microbiome suppression using vancomycin resulted in changes in multiple gut-derived uremic solutes. Future studies are needed to address whether reduction in those uremic solutes results in improvement of cardiovascular outcomes in ESKD patients.
| S-EPMC8343810 | biostudies-literature
Project description:Background Most patients on hemodialysis are treated thrice weekly even if they have residual kidney function, in part because uncertainty remains as to how residual function should be valued and incorporated into the dialysis prescription. Recent guidelines, however, have increased the weight assigned to residual function and thus reduced the treatment time required when it is present. Increasing the weight assigned to residual function may be justified by knowledge that the native kidney performs functions not replicated by dialysis, including solute removal by secretion. This study tested whether plasma concentrations of secreted solutes are as well controlled in patients with residual function on twice weekly hemodialysis as in anuric patients on thrice weekly hemodialysis.Methods We measured the plasma concentration and residual clearance, dialytic clearance, and removal rates for urea and the secreted solutes hippurate, phenylacetylglutamine, indoxyl sulfate, and p-cresol sulfate in nine patients on twice weekly hemodialysis and nine patients on thrice weekly hemodialysis.Results Compared with anuric patients on thrice weekly dialysis with the same standard Kt/Vurea, patients on twice weekly hemodialysis had lower hippurate and phenylacetylglutamine concentrations and similar indoxyl sulfate and p-cresol sulfate concentrations. Mathematical modeling revealed that residual secretory function accounted for the observed pattern of solute concentrations.Conclusions Plasma concentrations of secreted solutes can be well controlled by twice weekly hemodialysis in patients with residual kidney function. This result supports further study of residual kidney function value and the inclusion of this function in dialysis adequacy measures.
| S-EPMC6050930 | biostudies-literature
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.
| S-EPMC5823377 | biostudies-literature
Project description:Linoleic acid (LA, 18:2n-6) is the most abundant polyunsaturated fatty acid in the North American diet and is a precursor to circulating bioactive fatty acid metabolites implicated in brain disorders. This exploratory study tested the effects of increasing dietary LA on plasma and cerebral cortex metabolites derived from LA, its elongation-desaturation products dihomo-gamma linolenic (DGLA, 20:3n-6) acid and arachidonic acid (AA, 20:4n-6), as well as omega-3 alpha-linolenic (?-LNA, 18:3n-3), eicosapentaenoic (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3). Plasma and cortex were obtained from rats fed a 0.4%, 5.2% or 10.5% energy LA diet for 15 weeks and subjected to liquid chromatography tandem mass spectrometry analysis. Total oxylipin concentrations, representing the esterified and unesterified pool, and unesterified oxylipins derived from LA and AA were significantly increased and EPA metabolites decreased in plasma at 5.2% or 10.5% energy LA compared to 0.4% energy LA. Unesterified plasma DHA metabolites also decreased at 10.5% energy LA. In cortex, total and unesterified LA and AA metabolites increased and unesterified EPA metabolites decreased at 5.2% or 10.5% LA. DGLA and ?-LNA metabolites did not significantly change in plasma or cortex. Dietary LA lowering represents a feasible approach for targeting plasma and brain LA, AA, EPA or DHA-derived metabolite concentrations.
| S-EPMC5106341 | biostudies-literature
Project description:Background and objectivesNumerous substances accumulate in the body in uremia but those contributing to cardiovascular morbidity and mortality in dialysis patients are still undefined. We examined the association of baseline free levels of four organic solutes that are secreted in the native kidney - p-cresol sulfate, indoxyl sulfate, hippurate and phenylacetylglutamine - with outcomes in hemodialysis patients.Design, setting, participants and measurementsWe measured these solutes in stored specimens from 394 participants of a US national prospective cohort study of incident dialysis patients. We examined the relation of each solute and a combined solute index to cardiovascular mortality and morbidity (first cardiovascular event) using Cox proportional hazards regression adjusted for demographics, comorbidities, clinical factors and laboratory tests including Kt/VUREA.ResultsMean age of the patients was 57 years, 65% were white and 55% were male. In fully adjusted models, a higher p-cresol sulfate level was associated with a greater risk (HR per SD increase; 95% CI) of cardiovascular mortality (1.62; 1.17-2.25; p=0.004) and first cardiovascular event (1.60; 1.23-2.08; p<0.001). A higher phenylacetylglutamine level was associated with a greater risk of first cardiovascular event (1.37; 1.18-1.58; p<0.001). Patients in the highest quintile of the combined solute index had a 96% greater risk of cardiovascular mortality (1.96; 1.05-3.68; p=0.04) and 62% greater risk of first cardiovascular event (1.62; 1.12-2.35; p=0.01) compared with patients in the lowest quintile. Results were robust in sensitivity analyses.ConclusionsFree levels of uremic solutes that are secreted by the native kidney are associated with a higher risk of cardiovascular morbidity and mortality in incident hemodialysis patients.
| S-EPMC4418712 | biostudies-literature
Project description:Copeptin is increasingly used in epidemiological studies as a substitute for vasopressin. The effect of renal function per se on copeptin and vasopressin concentrations as well as their ratio have, however, not been well described.Copeptin and vasopressin levels were measured in 127 patients with various stages of chronic kidney disease, including 42 hemodialysis patients and 16 healthy participants in this observational study. Linear (segmental) regression analyses were performed to assess the association between renal function and copeptin, vasopressin and the C/V ratio. In addition, clearance of copeptin and vasopressin by hemodialysis was calculated.Both copeptin and vasopressin levels were higher when renal function was lower, and both showed associations with plasma osmolality. The C/V ratio was stable across renal function in subjects with an eGFR >28 ml/min per 1.73 m2. In contrast, the C/V ratio increased with worsening renal function in patients with eGFR ?28 ml/min per 1.73 m2. During hemodialysis, the initial decrease in vasopressin levels was greater compared with copeptin and, consequently, the C/V ratio increased. This was, at least in part, explained by a greater dialytic clearance of vasopressin compared with copeptin.Our data indicate that copeptin is a reliable substitute for vasopressin in subjects with an eGFR >28 ml/min per 1.73 m2, whereas at an eGFR ?28 ml/min per 1.73 m2, that is, CKD stages 4 and 5, a correction for renal function is required in epidemiological studies that use copeptin as a marker for vasopressin. Intradialytic copeptin levels do not adequately reflect vasopressin levels because vasopressin clearance by hemodialysis is higher than that of copeptin.
| S-EPMC5678637 | biostudies-other
Project description:IntroductionThere is increasing evidence that the microbiome contributes to esophageal disease. Diet, especially fiber and fat intake, is a known potent modifier of the colonic microbiome, but its impact on the esophageal microbiome is not well described. We hypothesized that dietary fiber and fat intake would be associated with a distinct esophageal microbiome.MethodsWe collected esophageal samples from 47 ambulatory patients scheduled to undergo endoscopy who completed a validated food frequency questionnaire quantifying dietary fiber and fat intake. Using 16S high-throughput sequencing, we determined composition of the esophageal microbiome and predicted functional capacity of microbiota based on fiber and fat intake.ResultsAmong all samples, the most abundant phyla were Firmicutes (54.0%), Proteobacteria (19.0%), Bacteroidetes (17.0%), Actinobacteria (5.2%), and Fusobacteria (4.3%). Increasing fiber intake was significantly associated with increasing relative abundance of Firmicutes (p = 0.04) and decreasing relative abundance of Gram-negative bacteria overall (p = 0.03). Low fiber intake was associated with increased relative abundance of several Gram-negative bacteria, including Prevotella, Neisseria, and Eikenella. Several predicted metabolic pathways differed between highest and lowest quartile of fiber intake. Fat intake was associated with altered relative abundance of few taxa, with no alterations at the phylum level and no changes in microbiome functional composition.ConclusionsDietary fiber, but not fat, intake was associated with a distinct esophageal microbiome. Diet should be considered an important modifier of the esophageal microbiome in future studies. Studies are also needed to elucidate how the effects of dietary fiber on the esophageal microbiome may contribute to esophageal disease.
| S-EPMC6200756 | biostudies-literature
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.
| S-EPMC6528572 | biostudies-literature
Project description:The semipermeable capillary walls not only enable the removal of excess body water and solutes during hemodialysis (HD) but also provide an essential mechanism for maintaining cardiovascular homeostasis. Here, we investigated transcapillary transport processes on the whole-body level using the three-pore model of the capillary endothelium with large, small and ultrasmall pores. The transcapillary transport and cardiovascular response to a 4-h hemodialysis (HD) with 2 L ultrafiltration were analyzed by simulations in a virtual patient using the three-pore model of the capillary wall integrated in the whole-body compartmental model of the cardiovascular system with baroreflex mechanisms. The three-pore model revealed substantial changes during HD in the magnitude and direction of transcapillary water flows through small and ultrasmall pores and associated changes in the transcapillary convective transport of proteins and small solutes. The fraction of total capillary hydraulic conductivity attributed to ultrasmall pores was found to play an important role in the transcapillary water transport during HD thus influencing the cardiovascular response to HD. The presented model provides a novel computational framework for a detailed analysis of microvascular exchange during HD and as such may contribute to a better understanding of dialysis-induced changes in blood volume and blood pressure.
| S-EPMC7603324 | biostudies-literature