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J Am Soc Nephrol DOI:10.1681/ASN.2009111132

Metabolite profiling identifies markers of uremia.

Publication TypeJournal Article
Year of Publication2010
AuthorsRhee, EP, Souza, A, Farrell, L, Pollak, MR, Lewis, GD, Steele, DJR, Thadhani, R, Clish, CB, Greka, A, Gerszten, RE
JournalJ Am Soc Nephrol
Date Published2010 Jun
KeywordsAged, Biogenic Amines, Biomarkers, Case-Control Studies, Dicarboxylic Acids, Female, Humans, Kidney Failure, Chronic, Male, Middle Aged, Nucleotides, Phenols, Renal Dialysis, Sphingomyelins, Triglycerides, Uremia

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.


Alternate JournalJ. Am. Soc. Nephrol.
PubMed ID20378825
PubMed Central IDPMC2900954
Grant ListK23 HL091106 / HL / NHLBI NIH HHS / United States
UL1 RR025758 / RR / NCRR NIH HHS / United States
T32 DK00754023 / DK / NIDDK NIH HHS / United States
UL1 RR025758-01 / RR / NCRR NIH HHS / United States