Development of an immunoassay for the kidney-specific protein myo-inositol oxygenase, a potential biomarker of acute kidney injury.
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.
Department of Pathology and Immunology, Division of Anatomic and Molecular Pathology.
Joseph P
JP
Gaut
Dan L
DL
Crimmins
Matt F
MF
Ohlendorf
Christina M
CM
Lockwood
Terry A
TA
Griest
Nancy A
NA
Brada
Masato
M
Hoshi
Bryan
B
Sato
Richard S
RS
Hotchkiss
Sanjay
S
Jain
Jack H
JH
Ladenson
D058186:Acute Kidney Injury / Q000097:blood* / Q000201:enzymology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western; D016638:Critical Illness; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D007150:Immunohistochemistry; D050562:Inositol Oxygenase; D008297:Male; D051379:Mice; D010105:Oxygenases / Q000097:blood* / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D012333:RNA, Messenger; D010105:Oxygenases; D050562:Inositol Oxygenase; C485890:MIOX protein, human