No new cases of nephrogenic systemic fibrosis occurred at two large tertiary care facilities after more restrictive policies on the use of gadolinium-based contrast agents were introduced.
Before the changes, the incidence of nephrogenic systemic fibrosis (NSF) was 1 in 33 in high-risk patients. In patients on dialysis, the incidence of NSF was 1 in 35, according Dr. Ersan Altun, a radiologist at the University of North Carolina in Chapel Hill, and his coauthors.
“The absence of NSF cases in the postadoption period may reflect the effect of the use of different GBCAs [gadolinium-based contrast agents] and the adoption of restrictive GBCA policies on the incidence of NSF,” they wrote (Radiology 2009;253:689–96).
In 2006, reports to the Food and Drug Administration suggested a strong association between NSF and gadolinium-based contrast agents used in MRI. The exact mechanism remains unknown; however, gadolinium contrast agents vary in their dissociation rates and dissociation of the gadolinium ion from the chelating ligand may be a risk factor, the researchers said.
Cases of NSF were documented at two tertiary care centers for three periods: before the adoption of restrictive GBCA policies and a change in agents, during the transition period, and after the adoption of these changes.
The new policies included careful screening of patients for risk factors for NSF such as renal disease, hypertension, dialysis, and diabetes before they underwent gadolinium-enhanced MRI. If GBCA-enhanced imaging was unavoidable in a patient deemed to be at high risk, a half dose of gadobenate dimeglumine was used. The policies also specified greater use of other types of imaging that do not require contrast agents. In addition, gadolinium-enhanced MRI was not performed in pregnant women unless maternal survival was at stake, was not performed in any patient twice within 48 hours unless absolutely necessary, and was not done twice within 48 hours in any patient deemed to be at high risk of NSF.
The researchers used patient records at center A and ICD-9 codes for acute renal failure and chronic kidney disease (stages 3–5) to identify patients who were at risk for NSF and underwent gadolinium-enhanced MRI. At center B, the researchers used ICD-9 codes and patient records to identify dialysis patients who underwent gadolinium-enhanced MRI.
Before adoption of the changes, both centers used gadodiamide (Omniscan, GE Healthcare Inc.). After the adoption of the revised policies, both centers used either gadobenate dimeglumine (Multihance, Bracco Diagnostics Inc.) or gadopentetate dimeglumine (Magnevist, Bayer Healthcare Pharmaceuticals Inc.) Gadobenate was used for all MRI studies of adults, patients younger than 1 year, and pediatric patients at risk for the development of NSF. Gadopentetate was used for pediatric patients 1 year and older who were not at risk for NSF. Both agents have lower dissociation rates than gadodiamide.
NSF was diagnosed by clinical findings and histopathologic evaluation of deep-skin biopsy. The temporal relationship/interval between the administration of gadolinium-based contrast and onset of NSF was determined for each patient.
At center A, 35 patients with NSF were identified in the preadoption period; of these, 28 underwent gadolinium-enhanced MR only at center A and received only gadodiamide. The benchmark incidence of NSF at center A was 1/1,750 and the NSF incidence in high-risk patients was 1/33.
At center B, 14 patients with NSF were identified in the preadoption period; of these, 9 underwent gadolinium-enhanced MR only at center B and received only gadodiamide. The benchmark incidence of NSF at center B was 1/1,803 and the NSF incidence in dialysis patients was 1/35.
There were no cases of NSF in the transitional and postadoption periods at either center.
One coauthor received funding from GE Healthcare, Bayer Healthcare Pharmaceuticals, and Bracco