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.

Atherosclerotic renal artery stenosis is associated with elevated cell cycle arrest markers related to reduced renal blood flow and postcontrast hypoxia

“…Our results using BOLD MRI suggest that residual accumulation of deoxyhemoglobin after contrast imaging can persist for at least 24-27 h and extend results observed in experimental rat models that demonstrate renal hypoxia measured by BOLD MRI after injection of iodinated contrast [37]. Studies in the rat suggest that these changes were associated with AKI as measured by NGAL levels [38]. However, another study from the same authors reported that AKI after renal hypoxia in rats after contrast injection did not occur when the rats were pretreated with furosemide [39].…”

Perioperative Acute Kidney Injury

“…It has also been used to study changes in renal blood flow associated with CKD and hypertension 106–108 . Despite the utility of BOLD MRI in studying renal oxygenation and function in animal models of AKI 109,110 , one recent study evaluating BOLD MRI in the evaluation of AKI in humans found no correlation between MRI findings and GFR 111 . Another recently developed MRI technique known as diffusion-weighted imaging (DWI) detects the motion of water molecules within tissue, and has been used to assess renal fibrosis in both AKI and CKD 81 .…”

The History of MR Imaging as Seen through the Pages ofRadiology

“…risk of acute renal injury after stresses such as the intravenous administration of an iodinated contrast agent (120)(121)(122).…”