title: Efficacy of preventive interventions for iodinated contrast-induced acute kidney injury evaluated by intrarenal oxygenation as an early marker.
abstract: OBJECTIVE
  The objective of this study was to evaluate the effects of potential renoprotective interventions such as the administration of N-acetylcysteine (NAC; antioxidant) and furosemide (diuretic) on intrarenal oxygenation as evaluated by blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) in combination with urinary neutrophil gelatinase-associated lipocalin (NGAL) measurements.
  
  
  METHODS
  Rats received nitric oxide synthase inhibitor L-NAME (10 mg/kg) and cyclooxygenase inhibitor indomethacin (10 mg/kg) to induce the risk for developing iodinated contrast-induced acute kidney injury before receiving one of the interventions: NAC, furosemide, or placebo. One of the 3 iodinated contrast agents (iohexol, ioxaglate, or iodixanol) was then administered (1600-mg organic iodine per kilogram body weight). Fifty-four Sprague-Dawley rats were allocated in a random order into 9 groups on the basis of the intervention and the contrast agent received.Blood-oxygen-level-dependent MRI-weighted images were acquired on a Siemens 3.0-T scanner using a multiple gradient recalled echo sequence at baseline, after L-NAME, indomethacin, interventions or placebo, and iodinated contrast agents. Data acquisition and analysis were performed in a blind fashion. R2* (=1/T2*) maps were generated inline on the scanner. A mixed-effects growth curve model with first-order autoregressive variance-covariance was used to analyze the temporal data. Urinary NGAL, a marker of acute kidney injury, was measured at baseline, 2 and 4 hours after the contrast injection.
  
  
  RESULTS
  Compared with the placebo-treated rats, those treated with furosemide showed a significantly lower rate of increase in R2* (P < 0.05) in the renal inner stripe of the outer medulla. The rats treated with NAC showed a lower rate of increase in R2* compared with the controls, but the difference did not reach statistical significance. Urinary NGAL showed little to no increase in R2* after administration of iodixanol in the rats pretreated with furosemide but demonstrated significant increase in the rats pretreated with NAC or placebo (P < 0.05).
  
  
  CONCLUSIONS
  This is the first study to evaluate the effects of interventions to mitigate the deleterious effects of contrast media using BOLD MRI. The rate of increase in R2* after administration of iodinated contrast is associated with acute renal injury as evaluated by NGAL. Further studies are warranted to determine the optimum dose of furosemide and NAC for mitigating the ill effects of contrast media. Because NGAL has been shown to be useful in humans to document iodinated contrast-induced acute kidney injury, the method presented in this study using BOLD MRI and NGAL measurements can be translated to humans.
authors.affiliation: From the *Pritzker School of Medicine, University of Chicago; †Department of Radiology/Center for Advanced Imaging; ‡Department of Biomedical Engineering, Northwestern University; §Department of Obstetrics and Gynecology, ∥Center for Biomedical & Research Informatics, ¶Department of Radiation Medicine, NorthShore University HealthSystem, Evanston, IL; and #Department of Nephrology, University of Vermont, Burlington, VT.
authors.forename: Lu-Ping
authors.initials: LP
authors.lastname: Li
authors.forename: Jon
authors.initials: J
authors.lastname: Thacker
authors.forename: Jing
authors.initials: J
authors.lastname: Lu
authors.forename: Tammy
authors.initials: T
authors.lastname: Franklin
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.forename: Maria V
authors.initials: MV
authors.lastname: Papadopoulou
authors.forename: Richard
authors.initials: R
authors.lastname: Solomon
authors.forename: Pottumarthi V
authors.initials: PV
authors.lastname: Prasad
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D058186:Acute Kidney Injury / Q000097:blood / Q000175:diagnosis* / Q000209:etiology / Q000517:prevention & control*; D000209:Acute-Phase Proteins / Q000652:urine; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D003287:Contrast Media / Q000008:administration & dosage / Q000009:adverse effects*; D004195:Disease Models, Animal; D004232:Diuretics / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005665:Furosemide / Q000494:pharmacology*; D007472:Iohexol / Q000008:administration & dosage; D007485:Ioxaglic Acid / Q000008:administration & dosage; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D010100:Oxygen / Q000097:blood*; D011518:Proto-Oncogene Proteins / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D014283:Triiodobenzoic Acids / Q000008:administration & dosage
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D003287:Contrast Media; D004232:Diuretics; D016166:Free Radical Scavengers; C097278:Lcn2 protein, rat; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D014283:Triiodobenzoic Acids; D007472:Iohexol; D005665:Furosemide; C044834:iodixanol; D010100:Oxygen; D000111:Acetylcysteine; D007485:Ioxaglic Acid