title: Evaluation of intrarenal oxygenation in iodinated contrast-induced acute kidney injury-susceptible rats by blood oxygen level-dependent magnetic resonance imaging.
abstract: OBJECTIVE
  The objectives of this study were to evaluate differences in intrarenal oxygenation as assessed by blood oxygen level-dependent (BOLD) magnetic resonance imaging in contrast-induced acute kidney injury (CIAKI)-susceptible rats when using 4 contrast media with different physicochemical properties and to demonstrate the feasibility of acquiring urinary neutrophil gelatinase-associated lipocalin (NGAL) levels as a marker of CIAKI in this model.
  
  
  METHODS
  Our institutional animal care and use committee approved the study. Sixty-six Sprague-Dawley rats were divided into CIAKI-susceptible groups (received nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester [10 mg/kg] and cycloxygenase inhibitor indomethacin [10mg/kg]) and control groups (received saline instead). One of the 4 iodinated contrast agents (iothalamate, iohexol, ioxaglate, or iodixanol) was then administered (1600-mg organic iodine per kilogram of body weight). Multiple blood oxygen level-dependent magnetic resonance images were acquired on a Siemens 3.0-T scanner using a multiple gradient recalled echo sequence at baseline, after N-nitro-L-arginine methyl ester (or saline), indomethacin (or saline), and iodinated contrast agent (or placebo). R2* (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 kidney injury (unlike serum creatinine), was measured 4 hours after contrast injection in the 2 subgroups.
  
  
  RESULTS
  Differences in blood oxygen level-dependent magnetic resonance imaging results between the contrast media were observed in all 4 renal regions. However, the inner stripe of the outer medulla (ISOM) showed the most pronounced changes in the CIAKI-susceptible group and R2* increased significantly (P<0.01) over time with all 4 contrast media. In the control groups, only iodixanol showed an increase in R2* (P<0.05) over time. There was an agreement between increases in NGAL and R2* values in ISOM.
  
  
  CONCLUSIONS
  In rats susceptible to CIAKI, those receiving contrast media had significant increases in R2* in renal ISOM compared with those receiving placebo. The agreement between NGAL and R2* values in the ISOM suggests that the observed immediate increase in R2* after contrast injection may be the earliest biomarker of renal injury. Further studies are necessary to establish threshold values of R2* associated with acute kidney injury and address the specificity of R2* to renal oxygenation status.
authors.affiliation: From the *Department of Radiology/Center for Advanced Imaging, †University of Chicago Pritzker School of Medicine, Chicago; ‡Department of Obstetrics and Gynaecology, §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: Jing
authors.initials: J
authors.lastname: Lu
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.forename: Maria V
authors.initials: MV
authors.lastname: Papadopoulou
authors.forename: Tammy
authors.initials: T
authors.lastname: Franklin
authors.forename: Ujala
authors.initials: U
authors.lastname: Bokhary
authors.forename: Richard
authors.initials: R
authors.lastname: Solomon
authors.forename: Anindya
authors.initials: A
authors.lastname: Sen
authors.forename: Pottumarthi V
authors.initials: PV
authors.lastname: Prasad
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood* / Q000139:chemically induced* / Q000175:diagnosis; D000209:Acute-Phase Proteins / Q000652:urine; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D003287:Contrast Media / Q000009:adverse effects*; D005240:Feasibility Studies; D007472:Iohexol / Q000009:adverse effects; D007483:Iothalamic Acid / Q000009:adverse effects; D007485:Ioxaglic Acid / Q000009:adverse effects; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood / Q000652:urine; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D010100:Oxygen / Q000097:blood*; D011518:Proto-Oncogene Proteins / Q000097:blood / Q000652:urine; D017207:Rats, Sprague-Dawley; D014283:Triiodobenzoic Acids / Q000009:adverse effects
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D003287:Contrast Media; C097278:Lcn2 protein, rat; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D014283:Triiodobenzoic Acids; D007483:Iothalamic Acid; D007472:Iohexol; C044834:iodixanol; D010100:Oxygen; D007485:Ioxaglic Acid