New cases of nephrogenic systemic fibrosis drop

June 10, 2008

A status report on nephrogenic systemic fibrosis suggests that new cases of the rare but devastating skin disease associated with exposure to gadolinium-based MRI contrast media have slowed to a trickle since the introduction of regulatory restrictions in the U.S. and Europe in 2007.

A status report on nephrogenic systemic fibrosis suggests that new cases of the rare but devastating skin disease associated with exposure to gadolinium-based MRI contrast media have slowed to a trickle since the introduction of regulatory restrictions in the U.S. and Europe in 2007.

Speaking at an NSF update at the 2008 International Society for Magnetic Resonance in Medicine meeting, Dr. Tim Leiner, chair of the ISMRM working group on NSF, described data from GE Healthcare that suggest that the number of new cases associated with Omniscan (gadodiamide) dropped from a peak of 58 cases in 2006 to 19 cases in 2007.

No confirmed cases of NSF were reported between August 2007 and Leiner's presentation in early May. The final nine suspected cases in 2007 were first reported by law firms, rather than medical institutions or physicians, he said.

The FDA has required manufacturers of the five gadolinium-based MR agents in the U.S. to carry a black box warning describing the risk of NSF since May 23, 2007. The warnings apply to Bayer Schering Pharma (Magnevist), Bracco (MultiHance and ProHance), GE (Omniscan), and Mallinckrodt (OptiMark).

The warnings inform users that patients with severe kidney insufficiency who received gadolinium-based agents are at risk for developing NSF. The warning also applies to patients awaiting liver transplantation or living with chronic liver disease. The European Union introduced a strict contraindication for the use of Omniscan in patients with severe renal failure and an advisory for all gadolinium products in 2007.

Leiner, a radiologist with the cardiovascular research institute at Maastricht University Hospital in the Netherlands, noted that 532 confirmed and suspected cases had been reported as of May 2008.

Nonionic linear chelates such an Omniscan and Magnevist are the least chemically stable of the commercially available products, and they are associated with most cases of NSF. Best-selling Magnevist has been linked with 23% of the cases. The second-best seller, Omniscan, has been associated with 69% of the cases. Only two cases appear to have been associated with Vasovist, Gadovist, or Primovist, three ionic macrocyclic agents that are not approved for marketing in the U.S.

Physician concern about the disease should not lead to the denial of justified MRI examinations, Leiner said.

At least 90% of the cases have involved patients with stage 4 or 5 chronic renal disease. Most NSF patients are on dialysis. Several cases were reported involving patients in acute renal failure at the time gadolinium contrast was injected.

Liver transplantation may be an independent risk factor, though results from a literature review presented by Dr. Sameer M. Mazhar of the University of California, San Diego at the ISMRM meeting indicated that concern about a link with liver disease stemmed from the experience of a single patient.

Leiner noted that immature renal function has examined as a possible risk factor, but no known cases of NSF have been identified among patients younger than age eight.

Some ancedotal reports involve patients who were not exposed to gadolinium before developing the disease, but none of the biopsies taken from these patients were analyzed for gadolinium content. The veracity of these reports is still open to question, he said.

The risk for developing NSF is still not well defined because the reported number of cases may over- or underestimate true prevalence. Accurate estimates of risk are lacking because of uncertainties about the number of patients at risk who were dosed. Still, the apparent risk for developing NSF appears to fall between one in every 100,000 to one in one million patients in an unselected population, according to Leiner. Experts suspect that overall incidence has been underreported.

The benefit of dialysis for prevention of NSF among at-risk patients who received a gadolinium-based contrast agent has not been established, Leiner said. He made note, however, of the European Society of Urogenital Radiology's recommendations for such patients.

For at-risk patients who have not undergone hemodialysis, the ESUR recommends macrocyclic gadolinium-based contrast injected in the lowest possible doses if no other alternative imaging modality is deemed satisfactory. Hemodialysis should not be initiated for the sole purpose of eliminating gadolinium-based contrast medium because of the high morbidity associated with hemodialysis alone.

For patients already on hemodialysis, the ESUR recommends hemodialysis within three hours after gadolinium-based contrast injection, with at least nine hours of hemodialysis to remove gadolinium in circulation.

Leiner criticized American College of Radiology guidelines asking physicians to consider dialysis for patients with an estimated glomerular filtration rate of less than 60.

"That guideline in my opinion is not supported by the number of cases we saw in that category," he said.

Contrast-enhanced CT could introduce more risks than it eliminates, especially if the physician has access to a macrocyclic MRI agent or one of the linearly stable agents assocaited with low rates of adverse events, Leiner said.

"Simple measures such as using macrocyclic agent can help you prevent NSF in patients with severe renal dysfunction," Leiner said.

For more information from the Diagnostic Imaging archives:
NSF discovery process may expose lax record-keepingKaiser study of 3.3 million members finds single case of NSFNSF's underlying cause remain hard to graspNew recommendations target NSF risk