Fumarase activity: an in vivo and in vitro biomarker for acute kidney injury: an in vivo and in vitro biomarker for acute kidney injury

Per Mose Nielsen, Abubakr Eldirdiri, Lotte Bonde Bertelsen, Hans Stodkilde Jorgensen, Jan Henrik Ardenkjær-Larsen, Christoffer Laustsen

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    Abstract

    Renal ischemia/reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI), and at present, there is a lack of reliable biomarkers that can diagnose AKI and measure early progression because the commonly used methods cannot evaluate single-kidney IRI. Hyperpolarized [1,4-C-13(2)] fumarate conversion to [1,4-C-13(2)] malate by fumarase has been proposed as a measure of necrosis in rat tumor models and in chemically induced AKI rats. Here we show that the degradation of cell membranes in connection with necrosis leads to elevated fumarase activity in plasma and urine and secondly that hyperpolarized [1,4-C-13(2)] malate production 24 h after reperfusion correlates with renal necrosis in a 40-min unilateral ischemic rat model. Fumarase activity screening on bio-fluids can detect injury severity, in bilateral as well as unilateral AKI models, differentiating moderate and severe AKI as well as short-and long-term AKI. Furthermore after verification of renal injury by bio-fluid analysis the precise injury location can be monitored by in vivo measurements of the fumarase activity non-invasively by hyperpolarized [1,4-C-13] fumarate MR imaging. The combined in vitro and in vivo biomarker of AKI responds to the essential requirements for a new reliable biomarker of AKI.
    Original languageEnglish
    Article number40812
    JournalScientific Reports
    Volume7
    Number of pages10
    ISSN2045-2322
    DOIs
    Publication statusPublished - 2017

    Keywords

    • Multidisciplinary
    • Reperfusion Injury
    • Genetics - Animal
    • Biochemistry studies - Nucleic acids, purines and pyrimidines
    • Enzymes - General and comparative studies: coenzymes
    • Cardiovascular system - Blood vessel pathology
    • Blood - Blood and lymph studies
    • Blood - Blood cell studies
    • Urinary system - Physiology and biochemistry
    • Urinary system - Pathology
    • Animals, Chordates, Mammals, Nonhuman Vertebrates, Nonhuman Mammals, Rodents, Vertebrates
    • enzyme activity
    • necrosis
    • MRI

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