Development of an immunoassay for the kidney-specific protein myo-inositol oxygenase, a potential biomarker of acute kidney injury

Joseph P. Gaut, Dan L. Crimmins, Matt F. Ohlendorf, Christina M. Lockwood, Terry A. Griest, Nancy A. Brada, Masato Hoshi, Bryan Sato, Richard S. Hotchkiss, Sanjay Jain, Jack H. Ladenson

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Background: Acute kidney injury (AKI) affects 45% of critically ill patients, resulting in increased morbidity and mortality. The diagnostic standard, plasma creatinine, is nonspecific and may not increase until days after injury. There is significant need for a renalspecific AKI biomarker detectable early enough that there would be a potential window for therapeutic intervention. In this study, we sought to identify a renalspecific biomarker of AKI. methods: We analyzed gene expression data from normal mouse tissues to identify kidney-specific genes, one of which was Miox. We generated monoclonal antibodies to recombinant myo-inositol oxygenase (MIOX) and developed an immunoassay to quantify MIOX in plasma. The immunoassay was tested in animals and retrospectively in patients with and without AKI. results: Kidney tissue specificity of MIOX was supported by Western blot. Immunohistochemistry localized MIOX to the proximal renal tubule. Serum MIOX, undetectable at baseline, increased 24 h following AKI in mice. Plasma MIOX was increased in critically ill patients with AKI [mean (SD) 12.4 (4.3) ng/mL, n = 42] compared with patients without AKI [0.5 (0.3) ng/mL, n = 17] and was highest in patients with oliguric AKI [20.2 (7.5) ng/mL, n = 23]. Plasma MIOX increased 54.3 (3.8) h before the increase in creatinine. conclusions: MIOX is a renal-specific, proximal tubule protein that is increased in serum of animals and plasma of critically ill patients with AKI. MIOX preceded the increases in creatinine concentration by approximately 2 days in human patients. Large-scale studies are warrantedtofurther investigate MIOXas an AKI biomarker.

Original languageEnglish
Pages (from-to)747-757
Number of pages11
JournalClinical chemistry
Volume60
Issue number5
DOIs
StatePublished - May 2014

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