Metabolon, Inc., the leader in metabolomics, biomarker discovery and analysis, announces the publication of "Metabolomics Analysis Reveals Elevation of 3-Indoxyl Sulfate in Plasma and Brain during Chemically-induced Acute Kidney Injury in Mice: Investigation of Nicotinic Acid Receptor Agonists", in Toxicology and Applied Pharmacology (doi: 10.1016/j.taap.2011.05.015). The study was authored by Dr. Joanna R. Zgoda-Pols and colleagues at Merck Research Laboratories in New Jersey and scientists at Metabolon.
Early predictive biomarkers of acute kidney injury (AKI) are essential to identify nephrotoxicity in preclinical model species and, particularly, in human patients. To identify AKI biomarkers that could recognize AKI early as well as aid in a better mechanistic understanding of SCH 900424-induced AKI in mice, Metabolon and Merck toxicologists performed a global metabolomics study on mouse blood plasma and urine. The metabolomics study revealed that 3-indoxyl sulfate (3IS), a renal toxin that accumulates in blood of uremic patients or animals, is a more sensitive marker of SCH900424-induced renal toxicity than the traditional kidney toxicity biomarkers, creatinine or urea. Furthermore, accumulation of 3IS in blood or tissues was not observed when the animals were treated with a closely related structural analog of SCH900424 that does not induce AKI (negative control). Development of a 3IS-specific quantitative LC-MS assay to analyze biofluids and tissues allowed for measuring accumulation of 3IS in SCH900424-treated mice, validating the metabolomics results. In summary, this paper demonstrates the ability to use global metabolomics to discover a mechanistically linked early biomarker of AKI that was further validated in an independent specific assay using a negative control test article.