Cytotoxicity of Iodinated and Gadolinium-based Contrast Agents in Renal Tubular Cells at Angiographic Concentrations: In Vitro Study

Heinrich, Marc; Kuhlmann, Martin K.; Kohlbacher, Sonja; Scheer, Mario; Grgic, Aleksandar; Heckmann, Martina; Uder, Michael

doi:10.1148/radiol.2422060245

Cited by 89 publications

(75 citation statements)

References 53 publications

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“…10,[26][27][28][29][30] The findings from the trypan blue exclusion assay indicate that cell death can in part be explained by the osmolality of the ICM, as this increases with increasing osmolality, supported by regression analysis which showed a reasonably good correlation between the two (r 2 = 0.76). However, the three non-ionic monomers differ in their potential to induce cell death.…”

Section: Discussionmentioning

confidence: 88%

The Effects of the Iodinated X-Ray Contrast Media Iodixanol, Iohexol, Iopromide, and Ioversol on the Rat Kidney Epithelial Cell Line NRK 52-E

et al. 2011

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Nephrotoxicity, associated with the administration of iodinated X-ray contrast media (ICM), continues to be a major side effect in a significant number of vulnerable patients undergoing diagnostic X-ray imaging procedures. The molecular mechanisms underlying these adverse effects on the kidneys are unclear despite several decades of investigation. Side effects are more common after exposure to high-osmolar compared with low-osmolar ICM, suggesting that osmolality may be an important physical-chemical property related to nephrotoxicity. This investigation in cultured NRK 52-E cells, a cell line of renal origin, compares the in vitro toxicity of the iso-osmolal ICM iodixanol with the lowosmolal ICM iohexol, iopromide, and ioversol. The cellular toxicity was evaluated with the trypan blue exclusion assay, the MTT assay, and incidences of cell death. A qualitative assessment of vacuolation of the cultured NRK 52-E cells was taken as a measure of intracellular uptake of ICM. A difference in cell death incidence was observed between the iso-osmolal iodixanol and the low-osmolal iohexol, iopromide, and ioversol contrast media, with the isoosmolal iodixanol having the least effect in each of the in vitro systems tested. The osmolality of the contrast media appeared to be the major cause for the observed in vitro toxicity.

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Section: Discussionmentioning

confidence: 88%

The Effects of the Iodinated X-Ray Contrast Media Iodixanol, Iohexol, Iopromide, and Ioversol on the Rat Kidney Epithelial Cell Line NRK 52-E

et al. 2011

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“…Rats were housed at [23][24][25] C in a 12-h light/dark cycle with free access to standard rat chow and tap water. All animal experiments were performed with the permission from the Medical Ethics Committee of Tianjin Medical University and followed the protocol outlined in the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication No.…”

Section: Animalsmentioning

confidence: 99%

Role of ERK1/2 and JNK phosphorylation in iodine contrast agent-induced apoptosis in diabetic rat kidneys

Jiao

Liu

et al. 2015

Renal Failure

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Background: The risk of contrast-induced acute kidney injury (CIAKI) is significantly increased in patients with diabetes mellitus. This study aimed to investigate molecular mechanisms of contrast media-induced apoptosis in diabetic rat kidneys, especially the involvement of ERK1/2 and JNK signal pathways. Methods: Diabetic Sprague-Dawley rats were induced by intraperitoneal injection of streptozotocin. Ten weeks later the normal and diabetic rats were administered high-osmolar contrast media (HOCM; meglumine diatrizoate) or normal saline (10 mL/kg) injection for 2 consecutive days. At 24 h after the operation, the rats were sacrificed, the blood samples were collected for examining serum creatinine and the kidneys were collected for determining the expression of caspase-3 by immunohistochemistry and the expression of Bcl-2, Bax, upstream signal molecule p-JNK, and p-ERK1/2 by western blotting. Results: The serum creatinine was significantly increased in diabetes + contrast media group (DC group) after operation compared with in the diabetic group (D group; 103.89 ± 9.01 mmol/L vs. 71.52 ± 7.03 mmol/L, p50.05). While creatinine clearance rate (Ccr) was significantly decreased in DC group after operation (1.49 ± 0.33 mL/min vs. 2.60 ± 0.54 mL/min, p50.05). Especially, in the diabetic kidney, the expression of caspase-3 was also significantly increased after intravenous injection of HOCM compared with normal saline. The expression level of upstream signal molecule p-JNK protein was apparently increased, but p-ERK1/2 protein was significantly decreased (both p50.05). Conclusions: The ionic HOCM-induced renal cells apoptosis in diabetic rats through activating the caspase-3 apoptotic pathway, which might be mediated by upstream MAPK (inhibiting p-ERK1/2 expression and promoting p-JNK expression) signal pathways.

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“…For example, when cultured renal tubular cells were incubated with Gd-CM and I-CM, the degree of cytotoxicity was similar. 17 Nyman et al 19 report a significantly more pronounced decrease in GFR in animals given Gd-CM than in those given I-CM.…”

Section: Discussionmentioning

confidence: 98%

“…15 In fact, histological data from a few animal studies suggest that Gd-CM induces acute tubular necrosis and cytoplasmic vacuolization in renal tubular cells in several hours. [16][17][18] For the above reasons, we further used a less stringent criterion (a decrease >10% in GFR) for AKI. This may explain why we found a higher incidence of AKI after administration of Gd-CM at the doses for MRI and MRA examinations.…”

Section: Discussionmentioning

confidence: 99%

Risk of Acute Kidney Injury after Exposure to Gadolinium-Based Contrast in Patients with Renal Impairment

Chien

Wang

et al. 2011

Renal Failure

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Objectives: Gadolinium-based contrast media (Gd-CM) are reported to induce acute kidney injury (AKI) in a high-risk population group at the usual dose for magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) examinations. We assessed gadolinium-induced nephropathy in patients with renal impairment who underwent MRI or MRA examinations, and evaluated the risk factors. Materials and methods: In this retrospective study, 238 patients with baseline renal impairment, who received MRI or MRA examinations with Gd-CM, were recruited. After all other AKI causes-liver decompensation, severe heart failure, all kinds of shock, and severe sepsis-and patients on dialysis were excluded, 158 patients were enrolled. AKI was defined as a decrease in glomerular filtration rate (GFR) >10% of baseline data within 3 days after administration of Gd-CM. Regression analysis was used to find independent risk factors for gadolinium-induced AKI (Gd-AKI). Results: Twenty-six of the 158 patients (16.5%) developed Gd-AKI. There were no significant differences in gender, age, or baseline GFR between those who did and who did not develop AKI. Comorbid coronary artery disease, liver cirrhosis, diabetes mellitus, and hypertension were not significantly associated with the development of Gd-AKI. However, sepsis was an independent risk factor for Gd-AKI after multivariate regression analysis (adjusted odds ratio: 4.417; 95% confidence interval: 1.671-11.676, p = 0.03). Conclusions: It is potential AKI after administration of Gd-CM under sepsis condition at the dose for MRI and MRA examinations in patients with renal impairment. It is important to identify high-risk patients and closely monitor renal function after administration of Gd-CM.

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Cytotoxicity of Iodinated and Gadolinium-based Contrast Agents in Renal Tubular Cells at Angiographic Concentrations: In Vitro Study

Abstract: At angiographic concentrations, gadolinium-based contrast agents do not induce fewer cytotoxic effects on cultured renal tubular cells than does iomeprol.

Cited by 89 publications

References 53 publications

The Effects of the Iodinated X-Ray Contrast Media Iodixanol, Iohexol, Iopromide, and Ioversol on the Rat Kidney Epithelial Cell Line NRK 52-E

The Effects of the Iodinated X-Ray Contrast Media Iodixanol, Iohexol, Iopromide, and Ioversol on the Rat Kidney Epithelial Cell Line NRK 52-E

Role of ERK1/2 and JNK phosphorylation in iodine contrast agent-induced apoptosis in diabetic rat kidneys

Risk of Acute Kidney Injury after Exposure to Gadolinium-Based Contrast in Patients with Renal Impairment

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