Evaluation of intrarenal oxygenation in iodinated contrast-induced acute kidney injury-susceptible rats by blood oxygen level-dependent magnetic resonance imaging.

Abstract

OBJECTIVES:

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.

MATERIALS AND 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: Lu-Ping Li, Jing Lu, Ying Zhou, Maria V Papadopoulou, Tammy Franklin, Ujala Bokhary, Richard Solomon, Anindya Sen, Pottumarthi V Prasad
• Journal: Investigative radiology (Invest Radiol) Vol. 49 Issue 6 Pg. 403-10 (Jun 2014) ISSN: 1536-0210 [Electronic] United States
• PMID: 24566288 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Acute-Phase Proteins
• Biomarkers
• Contrast Media
• Lcn2 protein, rat
• Lipocalin-2
• Lipocalins
• Proto-Oncogene Proteins
• Triiodobenzoic Acids
• Iothalamic Acid
• Iohexol
• iodixanol
• Oxygen
• Ioxaglic Acid

Topics

• Acute Kidney Injury (blood, chemically induced, diagnosis)
• Acute-Phase Proteins (urine)
• Animals
• Biomarkers (blood, urine)
• Contrast Media (adverse effects)
• Feasibility Studies
• Iohexol (adverse effects)
• Iothalamic Acid (adverse effects)
• Ioxaglic Acid (adverse effects)
• Lipocalin-2
• Lipocalins (blood, urine)
• Magnetic Resonance Imaging (methods)
• Male
• Oxygen (blood)
• Proto-Oncogene Proteins (blood, urine)
• Rats, Sprague-Dawley
• Triiodobenzoic Acids (adverse effects)