Colonic Contribution to Uremic Solutes : Journal of the American Society of Nephrology (original) (raw)

Clinical Research

Aronov, Pavel A.*; Luo, Frank J.-G.†; Plummer, Natalie S.†; Quan, Zhe‡; Holmes, Susan§; Hostetter, Thomas H.‡; Meyer, Timothy W.†

*Vincent Coates Foundation Mass Spectrometry Laboratory, and

§Department of Statistics, Stanford University, Stanford, California;

†Departments of Medicine, Veterans Administration Palo Alto Health Sciences Center and Stanford University, Palo Alto, California; and

‡Albert Einstein College of Medicine, New York, New York

Correspondence: Timothy W. Meyer, Nephrology 111R, Palo Alto Veterans Administration Health Sciences Center, 3801 Miranda Avenue, Palo Alto, CA 94303. Phone: 650-852-3314; Fax: 650-852-3411; E-mail: [email protected]

Received December 1, 2010

Accepted April 10, 2011

Abstract

Microbes in the colon produce compounds, normally excreted by the kidneys, which are potential uremic toxins. Although _p_-cresol sulfate and indoxyl sulfate are well studied examples, few other compounds are known. Here, we compared plasma from hemodialysis patients with and without colons to identify and further characterize colon-derived uremic solutes. HPLC confirmed the colonic origin of _p_-cresol sulfate and indoxyl sulfate, but levels of hippurate, methylamine, and dimethylamine were not significantly lower in patients without colons. High-resolution mass spectrometry detected more than 1000 features in predialysis plasma samples. Hierarchical clustering based on these features clearly separated dialysis patients with and without colons. Compared with patients with colons, we identified more than 30 individual features in patients without colons that were either absent or present in lower concentration. Almost all of these features were more prominent in plasma from dialysis patients than normal subjects, suggesting that they represented uremic solutes. We used a panel of indole and phenyl standards to identify five colon-derived uremic solutes: α-phenylacetyl-l-glutamine, 5-hydroxyindole, indoxyl glucuronide, _p_-cresol sulfate, and indoxyl sulfate. However, compounds with accurate mass values matching most of the colon-derived solutes could not be found in standard metabolomic databases. These results suggest that colonic microbes may produce an important portion of uremic solutes, most of which remain unidentified.