Effect of Iodinated Contrast Medium in Diabetic Rat Kidneys as Evaluated by Blood-Oxygenation-Level–Dependent Magnetic Resonance Imaging and Urinary Neutrophil Gelatinase-Associated Lipocalin

Abstract

Objectives To assess if streptozotocin (STZ) induced diabetic rats develop iodinated contrast induced acute kidney injury (CIAKI). The intra-renal R2* (= 1/ T2*) was evaluated continuously before-during-after contrast administration. Renal injury was confirmed by urinary neutrophil gelatinase-associated lipocalin (uNGAL) measurements. Materials and Methods Six Sprague-Dawley rats were administered STZ to induce diabetes (Group 1). R2* was measured before, during, and after administration of iodixanol. R2* readings were sampled from four renal regions: inner medulla, inner stripe of outer medulla (ISOM), outer stripe of outer medulla, and cortex. Peak R2* and initial up-slope of R2* increase following iodinated contrast were calculated. Data from 12 non-diabetic rats pre-treated with nitric oxide synthase and prostaglandin inhibitors to induce susceptibility to CIAKI (pre-treatment model) from a previous study were re-analyzed for peak R2* and initial up-slope of R2* increase following contrast. Six of these animals received saline (Group 2) and the other six received furosemide (Group 3) prior to idoxianol. Results Peak R2* and initial up-slope of R2* increase were used as BOLD response parameters. R2* in ISOM were comparable in all three groups prior to administration of furosemide. Except for the furosemide group, ISOM showed a rapid increase in R2* immediately following contrast administration. Unlike the L-NAME & indomethacin treated groups, the diabetic group showed a quick reversal of R2* towards baseline measurements after contrast administration. Urinary NGAL indicated significant increase in diabetic rats 4 hours following contrast administration. The observed trends with peak R2* and initial up-slope of R2* increase in renal ISOM were in agreement with those of uNGAL. Conclusion The STZ induced diabetic rat may be suitable for studying the effects of iodinated contrast on renal oxygenation status and may mimic human condition closer than the pre-treatment model described before. The peak R2* value and initial up-slope of R2* in ISOM appear to be effective MRI markers to predict renal injury following administration of an iodinated contrast agent.

Resveratrol Protects Against Post-Contrast Acute Kidney Injury in Rabbits With Diabetic Nephropathy

“…Meanwhile, we hypothesized that an increase in blood flow was responsible for increased D * and f values observed in the kidneys of resveratrol-treated rabbits; resveratrol, as an activator of SIRT1, may significantly decrease renal vascular dysfunction. Moreover, the application of iohexol led to a prolonged increase of R2 * values and HIF-1α expression, which suggested that hypoxia may be a major factor associated with the early development of PC–AKI and was consistent with other studies (Li et al, 2015). The decrease in R2 * values may be attributed to the inhibition of hypoxia production induced by resveratrol during the diabetes stage, and the amplification of secondary hypoxia signaling after iohexol injection.…”

Evaluation of Renal Pathophysiological Processes Induced by an Iodinated Contrast Agent in a Diabetic Rabbit Model Using Intravoxel Incoherent Motion and Blood Oxygenation Level-Dependent Magnetic Resonance Imaging

“…With respect to contrast-induced kidney damage, we found that the R2 * was significantly higher in the diabetic rabbits compared to in the healthy rabbits, and these observations were correlated with HIF-1α levels. The CA administration aggravated physiological medullary hypoxia in an acute-on-diabetes renal failure compared to an acute-on-healthy renal failure (8). Chronic renal disease is a significant risk factor for acute renal dysfunction following renal hypoxia and toxicity (40).…”

“…Due to the rapid development of the functional magnetic resonance imaging (fMRI) methodology, it may be possible to acquire valuable information on the pathophysiology of CI-AKI when it follows the onset of diabetes in a patient (8). Preclinical studies have demonstrated that blood oxygenation level-dependent (BOLD) imaging could serve as a reliable noninvasive method to measure the renal oxygen content in both humans and animals (91011).…”

Effect of Repeated Injection of Iodixanol on Renal Function in Healthy Wistar Rats Using Functional MRI

“…Parametric images of R2 ∗ and ADC were analyzed on ADVANCE 4.6 Workstation software (General Electric Medical Systems). According to the study of Li et al [ 8 , 24 ], all layers of renal tissues and the corresponding R2 ∗ -weighted image were segmented into four regions, including cortex (CO), outer stripe of the outer medulla (OSOM), inner stripe of the outer medulla (ISOM), and inner medulla (IM) (Figures 2(a) and 2(b) ). In each kidney, a single region of interest (ROI) corresponding to the histological sections was placed by a manual segmentation of the coronal BOLD images and DWI images.…”