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BMC Nephrol DOI:10.1186/s12882-015-0100-y

Cross-sectional examination of metabolites and metabolic phenotypes in uremia.

Publication TypeJournal Article
Year of Publication2015
AuthorsKalim, S, Clish, CB, Deferio, JJ, Ortiz, G, Moffet, AS, Gerszten, RE, Thadhani, R, Rhee, EP
JournalBMC Nephrol
Date Published2015 Jul 07
KeywordsAged, Aged, 80 and over, Blood Pressure, Body Mass Index, Cholesterol, Cohort Studies, Cross-Sectional Studies, Diabetes Mellitus, Female, Humans, Kidney Failure, Chronic, Male, Metabolome, Middle Aged, Obesity, Prospective Studies, Renal Dialysis, Serum Albumin, Uremia

BACKGROUND: Although metabolomic approaches have begun to document numerous changes that arise in end stage renal disease (ESRD), how these alterations relate to established metabolic phenotypes in uremia is unknown.

METHODS: In 200 incident hemodialysis patients we used partial least squares discriminant analysis to identify which among 166 metabolites could best discriminate individuals with or without diabetes, and across tertiles of body mass index, serum albumin, total cholesterol, and systolic blood pressure.

RESULTS: Our data do not recapitulate metabolomic signatures of diabetes and obesity identified among individuals with normal renal function (e.g. elevations in branched chain and aromatic amino acids) and highlight several potential markers of diabetes status specific to ESRD, including xanthosine-5-phosphate and vanillylmandelic acid. Further, our data identify significant associations between elevated tryptophan and long-chain acylcarnitine levels and both decreased total cholesterol and systolic blood pressure in ESRD. Higher tryptophan levels were also associated with higher serum albumin levels, but this may reflect tryptophan's significant albumin binding. Finally, an examination of the uremic retention solutes captured by our platform in relation to 24 clinical phenotypes provides a framework for investigating mechanisms of uremic toxicity.

CONCLUSIONS: In sum, these studies leveraging metabolomic and metabolic phenotype data acquired in a well-characterized ESRD cohort demonstrate striking differences from metabolomics studies in the general population, and may provide clues to novel functional pathways in the ESRD population.


Alternate JournalBMC Nephrol
PubMed ID26149577
PubMed Central IDPMC4491861
Grant ListKL2 TR001100 / TR / NCATS NIH HHS / United States
R01 DK081572 / DK / NIDDK NIH HHS / United States
R01 HL098280 / HL / NHLBI NIH HHS / United States
KL2TR001100 / TR / NCATS NIH HHS / United States
K08-DK-090142 / DK / NIDDK NIH HHS / United States
K24 DK094872 / DK / NIDDK NIH HHS / United States
1R01 HL098280 / HL / NHLBI NIH HHS / United States
K08 DK090142 / DK / NIDDK NIH HHS / United States
2R01DK081572 / DK / NIDDK NIH HHS / United States