title: Preclinical Studies of a Kidney Safe Iodinated Contrast Agent.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Verrow Pharmaceuticals, Inc, Lenexa, KS.
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Rowe
authors.affiliation: Rowe Neurology Institute, Lenexa, KS.
authors.forename: Vernon D
authors.initials: VD
authors.lastname: Rowe
authors.affiliation: Rowe Neurology Institute, Lenexa, KS.
authors.forename: Sangita
authors.initials: S
authors.lastname: Biswas
authors.affiliation: Verrow Pharmaceuticals, Inc, Lenexa, KS.
authors.forename: Gerold
authors.initials: G
authors.lastname: Mosher
authors.affiliation: Rowe Neurology Institute, Lenexa, KS.
authors.forename: Lovella
authors.initials: L
authors.lastname: Insisienmay
authors.affiliation: Rowe Neurology Institute, Lenexa, KS.
authors.forename: Marlies K
authors.initials: MK
authors.lastname: Ozias
authors.affiliation: CorDynamics, Inc, Chicago, IL.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Gralinski
authors.affiliation: Rowe Neurology Institute, Lenexa, KS.
authors.forename: John
authors.initials: J
authors.lastname: Hunter
authors.affiliation: Rowe Neurology Institute, Lenexa, KS.
authors.forename: James S
authors.initials: JS
authors.lastname: Barnett
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000517:prevention & control*; D000818:Animals; D017209:Apoptosis; D002460:Cell Line / Q000187:drug effects; D003287:Contrast Media / Q000009:adverse effects* / Q000737:chemistry / Q000494:pharmacology; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D007472:Iohexol / Q000009:adverse effects* / Q000737:chemistry / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D017207:Rats, Sprague-Dawley; D047392:beta-Cyclodextrins / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D003287:Contrast Media; D047392:beta-Cyclodextrins; C093196:SBE4-beta-cyclodextrin; D007472:Iohexol
keywords: Contrast renal toxicity; acute kidney injury; iodinated contrast safety; kidney protection from contrast; safe contrast for interventional procedures