title: Assessment of early diabetic renal changes with hyperpolarized [1-(13) C]pyruvate.
abstract: BACKGROUND
  This experimental study explores a novel magnetic resonance imaging/spectroscopic (MRI/MRS) method that measures changes in renal metabolism in a diabetic rat model. This hyperpolarized metabolic MRI/MRS method allows monitoring of metabolic processes in seconds by >10 000-fold enhancement of the MR signal. The method has shown that the conversion of pyruvate to bicarbonate, i.e. pyruvate dehydrogenase (PDH) activity, is significantly altered in the myocardium already at the onset of diabetes, and the predominant Warburg effect is a valuable cancer maker via the lactate dehydrogenase (LDH) activity. We hypothesize that a similar change in PDH and LDH could be found in the early diabetic kidney.
  
  
  METHODS
  In a streptozotocin rat model of type 1 diabetes, hyperpolarized (13) C-MRI and blood oxygenation level-dependent (1) H-MRI was employed to investigate the changes in renal metabolism in the diabetic and the control kidneys in vivo.
  
  
  RESULTS
  The diabetic kidney showed a 149% increase in the lactate/pyruvate ratio compared with the control rat kidney, whereas the bicarbonate/pyruvate ratio was unchanged between the diabetic and the control rat kidneys, consistent with literature findings. These metabolic findings paralleled a reduced intrarenal oxygen availability as found by blood oxygenation level-dependent MRI.
  
  
  CONCLUSIONS
  Hyperpolarized (13) C-MRI shows promise in the diagnosis and monitoring of early renal changes associated with diabetes, with the pyruvate/lactate ratio as an imaging biomarker for regional renal changes.
authors.affiliation: MR Research Centre, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: Christoffer
authors.initials: C
authors.lastname: Laustsen
authors.forename: Jakob Appel
authors.initials: JA
authors.lastname: Østergaard
authors.forename: Mette Hauge
authors.initials: MH
authors.lastname: Lauritzen
authors.forename: Rikke
authors.initials: R
authors.lastname: Nørregaard
authors.forename: Sean
authors.initials: S
authors.lastname: Bowen
authors.forename: Lise Vejby
authors.initials: LV
authors.lastname: Søgaard
authors.forename: Allan
authors.initials: A
authors.lastname: Flyvbjerg
authors.forename: Michael
authors.initials: M
authors.lastname: Pedersen
authors.forename: Jan Henrik
authors.initials: JH
authors.lastname: Ardenkjaer-Larsen
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D002247:Carbon Isotopes; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000652:urine; D005260:Female; D007668:Kidney / Q000378:metabolism* / Q000503:physiopathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D011188:Potassium / Q000378:metabolism; D030481:Pyruvate Dehydrogenase (Lipoamide) / Q000378:metabolism; D019289:Pyruvic Acid / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism
chemical_list: D001639:Bicarbonates; D002247:Carbon Isotopes; D019344:Lactic Acid; D019289:Pyruvic Acid; D012964:Sodium; D007770:L-Lactate Dehydrogenase; D030481:Pyruvate Dehydrogenase (Lipoamide); D011188:Potassium