| Metabolite profiling identifies markers of uremia. | |
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MedLine Citation:
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PMID: 20378825 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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ESRD is a state of small-molecule disarray. We applied liquid chromatography/tandem mass spectrometry-based metabolite profiling to survey>350 small molecules in 44 fasting subjects with ESRD, before and after hemodialysis, and in 10 age-matched, at-risk fasting control subjects. At baseline, increased levels of polar analytes and decreased levels of lipid analytes characterized uremic plasma. In addition to confirming the elevation of numerous previously identified uremic toxins, we identified several additional markers of ESRD, including dicarboxylic acids (adipate, malonate, methylmalonate, and maleate), biogenic amines, nucleotide derivatives, phenols, and sphingomyelins. The pattern of lipids was notable for a universal decrease in lower-molecular-weight triacylglycerols, and an increase in several intermediate-molecular-weight triacylglycerols in ESRD compared with controls; standard measurement of total triglycerides obscured this heterogeneity. These observations suggest disturbed triglyceride catabolism and/or beta-oxidation in ESRD. As expected, the hemodialysis procedure was associated with significant decreases in most polar analytes. Unexpected increases in several metabolites, however, indicated activation of a broad catabolic program, including glycolysis, lipolysis, ketosis, and nucleotide breakdown. In summary, this study demonstrates the application of metabolite profiling to identify markers of ESRD, provide perspective on uremic dyslipidemia, and broaden our understanding of the biochemical effects of hemodialysis. |
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Authors:
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Eugene P Rhee; Amanda Souza; Laurie Farrell; Martin R Pollak; Gregory D Lewis; David J R Steele; Ravi Thadhani; Clary B Clish; Anna Greka; Robert E Gerszten |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-04-08 |
Journal Detail:
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Title: Journal of the American Society of Nephrology : JASN Volume: 21 ISSN: 1533-3450 ISO Abbreviation: J. Am. Soc. Nephrol. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-31 Completed Date: 2010-06-21 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 9013836 Medline TA: J Am Soc Nephrol Country: United States |
Other Details:
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Languages: eng Pagination: 1041-1051 Citation Subset: IM |
Affiliation:
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Massachusetts General Hospital, 149 13th Street, 8th Floor, Boston, MA, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aged Biogenic Amines / blood Biological Markers / blood Case-Control Studies Dicarboxylic Acids / blood Female Humans Kidney Failure, Chronic / blood*, complications*, therapy Male Middle Aged Nucleotides / blood Phenols / blood Renal Dialysis Sphingomyelins / blood Triglycerides / blood Uremia / blood*, etiology* |
| Grant Support | |
ID/Acronym/Agency:
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K23 HL091106-04/HL/NHLBI NIH HHS; T32 DK00754023/DK/NIDDK NIH HHS; UL1 RR025758-01/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Biogenic Amines; 0/Biological Markers; 0/Dicarboxylic Acids; 0/Nucleotides; 0/Phenols; 0/Sphingomyelins; 0/Triglycerides |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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