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

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 renal-specific AKI biomarker detectable early enough that there would be a potential window for therapeutic intervention. In this study, we sought to identify a renal-specific 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 warranted to further investigate MIOX as an AKI biomarker.

• Authors: 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
• Journal: Clinical chemistry (Clin Chem) Vol. 60 Issue 5 Pg. 747-57 (May 2014) ISSN: 1530-8561 [Electronic] England
• PMID: 24486646 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antibodies, Monoclonal
• Biomarkers
• RNA, Messenger
• Oxygenases
• Inositol Oxygenase
• MIOX protein, human

Topics

• Acute Kidney Injury (blood, enzymology)
• Animals
• Antibodies, Monoclonal (immunology)
• Biomarkers (blood)
• Blotting, Western
• Critical Illness
• Female
• Humans
• Immunoassay (methods)
• Immunohistochemistry
• Inositol Oxygenase
• Male
• Mice
• Oxygenases (blood, genetics, immunology)
• RNA, Messenger (genetics)