title: In situ lactate dehydrogenase activity: a novel renal cortical imaging biomarker of tubular injury?
abstract: Renal ischemia-reperfusion injury is the state of which a tissue experiences injury after a phase of restrictive blood supply and recirculation. Ischemia-reperfusion injury (I/R-I) is a leading cause of acute kidney injury (AKI) in several disease states, including kidney transplantation, sepsis, and hypovolemic shock. The most common methods to evaluate AKI are creatinine clearance, plasma creatinine, blood urea nitrogen, or renal histology. However, currently, there are no precise methods to directly assess renal injury state noninvasively. Hyperpolarized13C-pyruvate MRI enables noninvasive accurate quantification of the in vivo conversion of pyruvate to lactate, alanine, and bicarbonate. In the present study, we investigated the in situ alterations of metabolic conversion of pyruvate to lactate, alanine, and bicarbonate in a unilateral I/R-I rat model with 30 min and 60 min of ischemia followed by 24 h of reperfusion. The pyruvate conversion was unaltered compared with sham in the 30 min I/R-I group, while a significant reduced metabolic conversion was found in the postischemic kidney after 60 min of ischemia. This indicates that after 30 min of ischemia, the kidney maintains normal metabolic function in spite of decreased kidney function, whereas the postischemic kidney after 60 min of ischemia show a generally reduced metabolic enzyme activity concomitant with a reduced kidney function. We have confidence that these findings can have a high prognostic value in prediction of kidney injury and the outcome of renal injury.
authors.affiliation: MRI Research Centre, Aarhus University Hospital, Aarhus N, Denmark; and.
authors.forename: Per Mose
authors.identifier: 0000-0001-9767-1852
authors.initials: PM
authors.lastname: Nielsen
authors.affiliation: MRI Research Centre, Aarhus University Hospital, Aarhus N, Denmark; and.
authors.forename: Christoffer
authors.initials: C
authors.lastname: Laustsen
authors.affiliation: MRI Research Centre, Aarhus University Hospital, Aarhus N, Denmark; and.
authors.forename: Lotte Bonde
authors.initials: LB
authors.lastname: Bertelsen
authors.affiliation: MRI Research Centre, Aarhus University Hospital, Aarhus N, Denmark; and.
authors.forename: Haiyun
authors.initials: H
authors.lastname: Qi
authors.affiliation: MRI Research Centre, Aarhus University Hospital, Aarhus N, Denmark; and.
authors.forename: Emmeli
authors.initials: E
authors.lastname: Mikkelsen
authors.affiliation: Department of Clinical Medicine, Aarhus University Hospital, Aarhus N, Denmark.
authors.forename: Marie Louise Vindvad
authors.initials: ML
authors.lastname: Kristensen
authors.affiliation: Department of Clinical Medicine, Aarhus University Hospital, Aarhus N, Denmark.
authors.forename: Rikke
authors.initials: R
authors.lastname: Nørregaard
authors.affiliation: MRI Research Centre, Aarhus University Hospital, Aarhus N, Denmark; and hsj@clin.au.dk.
authors.forename: Hans
authors.initials: H
authors.lastname: Stødkilde-Jørgensen
mesh_terms: D058186:Acute Kidney Injury / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D000409:Alanine / Q000378:metabolism; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002247:Carbon Isotopes; D004195:Disease Models, Animal; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism / Q000652:urine; D007684:Kidney Tubules / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D007770:L-Lactate Dehydrogenase / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D000080864:Lactate Dehydrogenase 5; D019344:Lactic Acid / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D011237:Predictive Value of Tests; D011379:Prognosis; D019289:Pyruvic Acid / Q000378:metabolism; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
chemical_list: D001639:Bicarbonates; D015415:Biomarkers; D002247:Carbon Isotopes; D007527:Isoenzymes; D019344:Lactic Acid; D019289:Pyruvic Acid; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; D000409:Alanine
keywords: MRI; hyperpolarization; ischemia-reperfusion injury; kidney; renal metabolism