Document Detail


Metabolite profiling identifies markers of uremia.
MedLine Citation:
PMID:  20378825     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-04-08
Journal Detail:
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:
Created Date:  2010-05-31     Completed Date:  2010-06-21     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  9013836     Medline TA:  J Am Soc Nephrol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1041-1051     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
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:
K23 HL091106/HL/NHLBI NIH HHS; T32 DK00754023/DK/NIDDK NIH HHS; UL1 RR025758-01/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
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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