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J Neuroimaging. 2016 Sep;26(5):511-8. doi: 10.1111/jon.12356. Epub 2016 May 12.

Preclinical Studies of a Kidney Safe Iodinated Contrast Agent.

Author information

1
Verrow Pharmaceuticals, Inc, Lenexa, KS.
2
Rowe Neurology Institute, Lenexa, KS.
3
CorDynamics, Inc, Chicago, IL.

Abstract

BACKGROUND AND PURPOSE:

Contrast-induced acute kidney injury (CI-AKI) is a serious complication of the use of iodinated contrast agents. This problem is particularly acute in interventional neurology and interventional cardiology, probably due to the intra-arterial route of injection, high contrast volumes, and preexisting risk factors of these patients. In an attempt to develop a contrast agent that is less damaging to the kidneys, we have studied the effects of adding a small amount of the substituted cyclodextrin, sulfobutyl-ether-β-cyclodextrin (SBECD), to iohexol in rodent models of renal toxicity.

METHODS:

Renally compromised mice and rats were injected with iohexol and iohexol-SBECD via the tail vein. The renal pathology, creatinine clearance, and survival benefits of iohexol-SBECD were studied. The safety of direct intra-arterial injection of the iohexol-SBECD formulation was studied in a dog heart model system. Mechanism of action studies in cell culture model using a human kidney cell line was performed using flow cytometry.

RESULTS:

Nephrotoxicity was significantly reduced using iohexol-SBECD compared to iohexol alone, at mole ratios of iohexol:SBECD of 1:0.025. SBECD increased survival from 50% to 88% in a rat survival study. In the dog heart model, iohexol-SBECD was safe. Cell culture studies suggest that SBECD interferes with the early stages of contrast-induced apoptosis in a human renal cell line.

CONCLUSION:

We have shown that the addition of a small amount of SBECD (one molecule of SBECD per 40 iohexol molecules) significantly protects rodent kidneys from CI-AKI. Further development of this new formulation of iodinated contrast is warranted.

KEYWORDS:

Contrast renal toxicity; acute kidney injury; iodinated contrast safety; kidney protection from contrast; safe contrast for interventional procedures

PMID:
27171830
PMCID:
PMC5084786
DOI:
10.1111/jon.12356
[Indexed for MEDLINE]
Free PMC Article

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