Document Detail


Colonic contribution to uremic solutes.
MedLine Citation:
PMID:  21784895     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Pavel A Aronov; Frank J-G Luo; Natalie S Plummer; Zhe Quan; Susan Holmes; Thomas H Hostetter; Timothy W Meyer
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-07-22
Journal Detail:
Title:  Journal of the American Society of Nephrology : JASN     Volume:  22     ISSN:  1533-3450     ISO Abbreviation:  J. Am. Soc. Nephrol.     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-09-01     Completed Date:  2011-10-31     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  9013836     Medline TA:  J Am Soc Nephrol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1769-76     Citation Subset:  IM    
Affiliation:
Vincent Coates Foundation Mass Spectrometry Laboratory, Stanford University, Stanford, California, USA.
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MeSH Terms
Descriptor/Qualifier:
Aged
Aged, 80 and over
Colon / chemistry*,  microbiology
Female
Humans
Kidney Failure, Chronic / blood*,  therapy
Male
Mass Spectrometry
Middle Aged
Renal Dialysis
Uremia / blood*
Grant Support
ID/Acronym/Agency:
DK7357/DK/NIDDK NIH HHS; R01 GM086884/GM/NIGMS NIH HHS; R01 GM086884/GM/NIGMS NIH HHS; R21 DK077326/DK/NIDDK NIH HHS; R21 DK084439/DK/NIDDK NIH HHS
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