Preclinical Studies of a Kidney Safe Iodinated Contrast Agent

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.