title: Fumarase activity: an in vivo and in vitro biomarker for acute kidney injury.
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 [1,4-13C2]fumarate conversion to [1,4-13C2]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 [1,4-13C2]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 [1,4-13C]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.
authors.affiliation: MR Research Centre, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: Per Mose
authors.initials: PM
authors.lastname: Nielsen
authors.affiliation: Department of Electrical Engineering, Technical University of Denmark, Kgs Lyngby, Denmark.
authors.forename: Abubakr
authors.initials: A
authors.lastname: Eldirdiri
authors.affiliation: MR Research Centre, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: Lotte Bonde
authors.initials: LB
authors.lastname: Bertelsen
authors.affiliation: MR Research Centre, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: Hans Stødkilde
authors.initials: HS
authors.lastname: Jørgensen
authors.affiliation: Department of Electrical Engineering, Technical University of Denmark, Kgs Lyngby, Denmark.|GE Healthcare, Broendby, Denmark.
authors.forename: Jan Henrik
authors.initials: JH
authors.lastname: Ardenkjaer-Larsen
authors.affiliation: MR Research Centre, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: Christoffer
authors.initials: C
authors.lastname: Laustsen
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood* / Q000473:pathology / Q000652:urine; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D005649:Fumarate Hydratase / Q000097:blood* / Q000378:metabolism / Q000652:urine; D008293:Malates / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015415:Biomarkers; D008293:Malates; C030298:malic acid; D005649:Fumarate Hydratase