NSF avoidance triggers debate

March 10, 2008

The controversial topic of nephrogenic systemic fibrosis drew a large crowd to a special focus session at the ECR. Delegates queued to quiz speakers about their recommendations for avoidance of the condition, ensuring a lively panel discussion.

The controversial topic of nephrogenic systemic fibrosis drew a large crowd to a special focus session at the ECR. Delegates queued to quiz speakers about their recommendations for avoidance of the condition, ensuring a lively panel discussion.

NSF has taken the medical community somewhat by surprise. The systemic disorder, which results in sclerodema-like skin discoloration and hardening, was first observed in patients in 1997. All cases reported to date have involved patients with advanced renal disease.

Radiologists' avid interest in NSF is due to its apparent link with gadolinium-containing contrast media. Most patients developing NSF had previously undergone imaging with a gadolinium-based agent.

The causal link between gadolinium-based agents and NSF is far from straightforward, however. Two cases have occurred in patients who have never received a gadolinium-containing contrast agent.

"It seems that gadolinium is a very powerful trigger, but NSF can also occur without the MRI agents," said Prof. Pontus Persson from the Institute of Physiology, Charité Medical University of Berlin.

Radiologists want to know how to prevent NSF. The first crucial step is to identify those patients who are at highest risk, that is, those with impaired renal function, said Prof. Sameh Morcos, a professor of radiology at the University of Sheffield in the U.K.

Regulatory bodies, including the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) and the FDA, recommend that doctors obtain an oral history and/or perform laboratory tests prior to gadolinium-enhanced MRI studies to identify any patients with renal dysfunction. Patients categorized as high risk are those with a glomerular filtration rate (GFR) lower than 30 mL/min. This all-important level can be derived from serum creatine measurements.

"As point-of-service techniques for measuring creatine become more widely available, then it will become increasingly harder to justify not doing a fingerstick test," said Dr. Shawn Cowper, an associate professor in the department of dermatology and pathology at Yale University and a renowned authority on NSF.

For patients with a low GFR, radiologists must decide if gadolinium-enhanced MRI is necessary. Studies that are clinically justified should be performed with a contrast agent that has a macrocyclical chemical structure and is less likely to release free gadolinium into the body, Morcos said. Most NSF cases have been associated with nonionic linear chelates such as gadodiamide, which are less stable. Just one case of NSF has been linked to a macrocyclic agent.

"Molecules with macrocyclic structure are like a birdcage. Once the gadolinium is inside the case, it is very difficult for it to come out," he said.

This strategy has already proved worthwhile at University Hospital Herlev in Denmark. Radiologists previously used gadodiamide when performing contrast-enhanced MRI on renal patients, said Prof. Henrik Thomsen, a professor of radiology at the Copenhagen-based hospital. A total of 28 NSF cases were recorded after 370 contrast injections. The team then switched to a macrocyclic agent with this patient group. More than 150 injections later, no cases of NSF have been observed.

"The same observation is now being reported by departments all over the world," he said.

Delegates were instructed not to use prophylactic hemodialysis as an NSF-prevention strategy. For patients already scheduled for hemodialysis, it may be prudent to carry that out shortly after the MRI examination. Patients on peritoneal dialysis are considered to be at greater risk of NSF, and they should be asked to do several rapid exchanges after MRI.

It may be reasonable to avoid injecting gadolinium in patients experiencing inflammatory events, owing to a possible link with the pathophysiological processes causing NSF, according to Morcos. This issue remains contentious.

Panelists rejected the suggestion that renal patients be injected with a chelate immediately after contrast-enhanced MRI to "mop up" any free gadolinium. This strategy has not been confirmed in animal trials and may cause more harm than good. The ligand may deplete the patient's natural reserves of copper or zinc and cause other unwanted side effects.

"Once the gadolinium is in there, there is not a lot you can do about it," Morcos said.