Effects of iodinated contrast agents on renal oxygenation level determined by blood oxygenation level dependent magnetic resonance imaging in rabbit models of type 1 and type 2 diabetic nephropathy

Abstract

Background: To evaluate the effects of contrast agents containing increasing concentrations of iodine on the renal oxygenation level determined by blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) in a rabbit model of diabetic nephropathy.

Methods: BOLD-MRI was performed using saline or iodinated (I) contrast agents (200, 240, 300, 350 and 400 mg I/mL) at 1, 24, 48, and 72 h after experimentally inducing type 2 diabetic nephropathy in rabbits. Differences in renal oxygenation levels between type 1 and type 2 diabetic nephropathy were also assessed by BOLD-MRI after injecting 400 mg I/mL of contrast agent.

Results: Contrast agents increased the R2* values of the renal cortex, outer medulla, and inner medulla to the maximum levels at 24 h. The R2* values then decreased to their lowest levels at 72 h. The R2* was highest following injection of 400 mg I/mL, especially in the outer medulla. The R2* values were not significantly different between types 1 and 2 diabetic nephropathy.

Conclusions: Iodinated contrast agents had the greatest influence on renal outer medulla oxygenation level at 24 h in type 2 diabetic nephropathy, with the greatest effects observed at the 400 mg I/mL dose level. There were no differences in BOLD-MRI values between type 1 and type 2 diabetic nephropathy after administering the contrast agent at 400 mg I/mL.

Figure 1

R2* values of the renal cortex (A), outer medulla (B), and inner medulla (C). Compared with the control group injected with physiological saline, the R2* values increased at 1 h and reached their peaks at 24 h and then decreased to the lowest values at 72 h in the five groups injected with iodinated contrast agents. The greatest changes occurred in the 400 mg I/mL group.

Figure 2

BOLD images obtained using 400 mg I/mL of contrast agent. (A) Control group. (B) Type 2 diabetic nephropathy group injected with saline. (C–F) Type 2 diabetic nephropathy group injected with 400 mg I/mL of contrast agent (C, 1 h; D, 24 h; E, 48 h; F, 72 h). Higher intensities on the R2* map indicate lower oxygenation of the underlying tissue. The intensity of the outer medulla of the diabetic kidney was greater than that in the cortex and inner medulla, which implies lower oxygenation of the outer medulla than the other regions.

Figure 3

Representative pathologic images. (A) Control group. (B) Type 2 diabetic nephropathy group injected with saline. (C–F) Type 2 diabetic nephropathy group injected with 400 mg I/mL of contrast agent (C, 1 h; D, 24 h; E, 48 h; F, 72 h). Changes in the glomerulus, renal tubules, and interstitium can be easily seen at each time point in the type 2 diabetic nephropathy group following injection of the contrast agent .

Figure 4

Representative immunohistochemistry images with pimonidazole staining. (A) Control group. (B) Type 2 diabetic nephropathy group injected with saline. (C–F) Type 2 diabetic nephropathy group injected with 400 mg I/mL of contrast agent (C, 1 h; D, 24 h; E, 48 h; F, 72 h). Pimonidazole staining was mainly localized in the renal outer medulla, especially at 24 h, while the renal cortex was lightly stained following injection of 400 mg I/mL of contrast agent.