Cross-sectional examination of metabolites and metabolic phenotypes in uremia

BMC Nephrology

Eugene P. Rhee³  Ravi Thadhani¹  Robert E. Gerszten²  Alexander S. Moffet¹  Guillermo Ortiz¹  Joseph J. Deferio¹  Clary B. Clish³  Sahir Kalim¹ 

[1] Division of Nephrology, Massachusetts General Hospital (MGH), 165 Cambridge Street, Suite 302, Boston 02114, MA, USA;Cardiovascular Research Center, MGH, Boston, MA, USA;Broad Institute, Cambridge, MA, USA

关键词: Uremic toxins;    Metabolomics;    Metabolism;    Dialysis;   

Others  :  1220022
DOI  :  10.1186/s12882-015-0100-y

 received in 2015-03-25, accepted in 2015-06-28,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Kalim et al.

【 图 表 】

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