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.
BACKGROUND:Acute kidney injury (AKI) affects 45% of critically illpatients, 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 illpatients 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 illpatients with AKI. MIOX preceded the increases in creatinine concentration by approximately 2 days in humanpatients. Large-scale studies are warranted to further investigate MIOX as an AKI biomarker.
Authors: R Hirschberg; J Kopple; P Lipsett; E Benjamin; J Minei; T Albertson; M Munger; M Metzler; G Zaloga; M Murray; S Lowry; J Conger; W McKeown; M O'shea; R Baughman; K Wood; M Haupt; R Kaiser; H Simms; D Warnock; W Summer; R Hintz; B Myers; K Haenftling; W Capra Journal: Kidney Int Date: 1999-06 Impact factor: 10.612
Authors: R L Allgren; T C Marbury; S N Rahman; L S Weisberg; A Z Fenves; R A Lafayette; R M Sweet; F C Genter; B R Kurnik; J D Conger; M H Sayegh Journal: N Engl J Med Date: 1997-03-20 Impact factor: 91.245
Authors: Justin Westhuyzen; Zoltan H Endre; Graham Reece; David M Reith; David Saltissi; Thomas J Morgan Journal: Nephrol Dial Transplant Date: 2003-03 Impact factor: 5.992
Authors: E Hu; Z Chen; T Fredrickson; M Gellai; M Jugus; L Contino; N Spurr; M Sims; W Halsey; S Van Horn; J Mao; G Sathe; D Brooks Journal: Am J Physiol Renal Physiol Date: 2000-09
Authors: James A Tumlin; Kevin W Finkel; Patrick T Murray; Joshua Samuels; George Cotsonis; Andrew D Shaw Journal: Am J Kidney Dis Date: 2005-07 Impact factor: 8.860
Authors: Eva C Schulte; Elisabeth Altmaier; Hannah S Berger; Kieu Trinh Do; Gabi Kastenmüller; Simone Wahl; Jerzy Adamski; Annette Peters; Jan Krumsiek; Karsten Suhre; Bernhard Haslinger; Andres Ceballos-Baumann; Christian Gieger; Juliane Winkelmann Journal: PLoS One Date: 2016-01-25 Impact factor: 3.240