In Renal Disease Patients, Think Twice Before MRI : Nephrogenic systemic fibrosis appears to increase with use of contrast agents, especially Omniscan.

Patients with stage III kidney disease or worse should not routinely be administered standard doses of gadolinium-based MR contrast agents, he recommended. This can have serious implications for the 35 million U.S. adults over age 65 years who have stage III or IV renal disease, many of whom require access to diagnostic MR services, Dr. Kanal said.

Exacerbating the problem is poor patient awareness of renal disease. According to Dr. Kanal, 97% of women and 82% of men with stage III chronic kidney disease are unaware that they have it. Thus asking patients whether they have renal disease may no longer be a sufficient screening method.

It is anticipated that a subset of patients at risk for renal disease (over age 60 years, history of hypertension, diabetes, renal disease or severe hepatic disease) will be required to have their glomerular filtration rates assessed before receiving gadolinium-based MR contrast agents. Since the risk of NSF may increase with cumulative dosing, neurologists should carefully consider the potential risk of serial contrast-enhanced scans when following patients.

While the FDA has applied black box warnings to all five MR contrast agents available in the United States, "the available data 'screams' that [the risk of NSF] is not equal for all the five FDA-approved MR contrast agents, and appears to be higher or far higher for Omniscan," he said, estimating that roughly 3%-7% of patients with end-stage renal disease receiving high-dose Omniscan will develop NSF.

"In my opinion, the present data are sufficiently compelling to avoid Omniscan administration in patients with any significant level of renal disease," he added.

For gadolinium to be tolerated by humans, it must be chelated to a ligand molecule, he said. The likelihood of the ligand dissociating from the gadolinium ion (leaving the toxic free Gd+3) is far from equal among these five agents, being far greater in Omniscan and Optimark than in Magnevist, Multihance, or Prohance, judging from findings from in vitro and some in vivo studies. Because nonionic Omniscan and Optimark have a far lower conditional stability constant than do Magnevist, Multihance, and Prohance at normal body pH, it is possible that this may be related to the perceived greater incidence of NSF in patients who received Omniscan, Dr. Kanal said.

Elevated levels of calcium, phosphate, copper, iron, and zinc, which can compete with the gadolinium ion for coupling with the ligand molecule, may also exacerbate the risk of toxicity.

"You need a radiologist who knows what she or he is doing in this area to help design the study in a manner that will decrease dosing yet still be as diagnostic as possible. Trust your radiologist and then follow his feedback and guidance," he commented.

If a dialysis patient must have a contrast MRI, the American College of Radiology guidelines recommend that the patient be taken to hemodialysis immediately following the completion of the MR examination in which the gadolinium-based MR contrast agent had been administered. Radiologists should compile a database of all patients with stage III or more severe kidney disease who have had contrast-enhanced MRIs and follow them to ensure that they do not develop NSF, Dr. Kanal recommended.

"It used to be that patients with renal failure would specifically be sent to MR because the contrast agents were not directly nephrotoxic at the doses used, whereas giving iodine to patients with renal disease could cause iodine-induced nephropathy. Now we have something else to worry about for patients with renal disease: NSF," Dr. Kanal said.

Patients with stage IIIkidney disease or worse shouldn't be routinely given standard doses of gadolinium-based agents. DR. KANAL

The skin on the arm of a patient with contrast agent-induced nephrogenic systemic fibrosis shows scleroderma-like changes, including scarring (which is usually painful), tightening, thickening, and discoloration. Nephrogenic systemic fibrosis is fulminant in about 5% of cases and can prove to be fatal within weeks. Courtesy Dr. Shawn Cowper