Microbes in the colon produce compounds, normally excreted by the kidneys, which are potential uremic toxins. Although p-cresol sulfate and indoxyl sulfate are well studied examples, few other compounds are known. Here, we compared plasma from hemodialysis patients with and without colons to identify and further characterize colon-derived uremic solutes. HPLC confirmed the colonic origin of p-cresol sulfate and indoxyl sulfate, but levels of hippurate, methylamine, and dimethylamine were not significantly lower in patients without colons. High-resolution mass spectrometry detected more than 1000 features in predialysis plasma samples. Hierarchical clustering based on these features clearly separated dialysis patients with and without colons. Compared with patients with colons, we identified more than 30 individual features in patients without colons that were either absent or present in lower concentration. Almost all of these features were more prominent in plasma from dialysis patients than normal subjects, suggesting that they represented uremic solutes. We used a panel of indole and phenyl standards to identify five colon-derived uremic solutes: α-phenylacetyl-l-glutamine, 5-hydroxyindole, indoxyl glucuronide, p-cresol sulfate, and indoxyl sulfate. However, compounds with accurate mass values matching most of the colon-derived solutes could not be found in standard metabolomic databases. These results suggest that colonic microbes may produce an important portion of uremic solutes, most of which remain unidentified.
SummaryBackground and objectives The uremic solutes p-cresol sulfate (PCS) and indoxyl sulfate (IS) are generated by colon bacteria acting on food components that escape absorption in the small bowel. The production of these potentially toxic compounds may thus be influenced by diet. This study examined whether production of PCS and IS is different in vegetarians and omnivores.Design, setting, participants, & measurements The production of PCS and IS was assessed by measuring their urinary excretion rates in participants with normal kidney function. Studies were carried out in 15 vegetarians and 11 individuals consuming an unrestricted diet. Participants recorded food intake over 4 days and collected urine over the final 2 days of each of two study periods, which were 1 month apart.Results Average PCS excretion was 62% lower (95% confidence interval [95% CI], 15-83) and average IS excretion was 58% lower (95% CI, 39-71) in vegetarians than in participants consuming an unrestricted diet. Food records revealed that lower excretion of PCS and IS in vegetarians was associated with a 69% higher (95% CI, 20-139) fiber intake and a 25% lower (95% CI, 3-42) protein intake. PCS and IS excretion rates varied widely among individual participants and were not closely correlated with each other but tended to remain stable in individual participants over 1 month.Conclusions PCS and IS production rates are markedly lower in vegetarians than in individuals consuming an unrestricted diet.
The removal of bound solutes can thus be increased by raising the dialyzate flow and dialyzer size above the low levels sufficient to achieve target Kt/V(urea) during extended treatment. Selectively increasing the clearance of bound solutes provides a potential means to test their toxicity.
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