Scottish researchers probe link between gadolinium and nephrogenic systemic fibrosis

A new six-year retrospective study has charted incidence of a rare and debilitating skin condition after gadolinium-enhanced MR in patients on kidney dialysis. Researchers found that nephrogenic systemic fibrosis may not surface for a very long time after gadolinium exposure and other unknown factors may play a role in disease development.

"It is difficult to say that there is a direct and sole role for gadolinium MR enhancement and NSF development," said Dr. Giles Roditi, a consultant radiologist at the Glasgow Royal Infirmary, who presented results at the ECR.

The FDA MedWatch program reported 112 cases of NSF, most of which were related to the gadolinium contrast agent Omniscan. Other sources have indicated that 200 to 400 cases have occurred worldwide.

The lack of a control patient population to allow comparisons has made data about incidence difficult to come by, Roditi said.

Using electronic medical records for virtually the whole population in West Scotland, the researchers performed a retrospective review of dialysis patients. They also interviewed dermatologists and radiologists involved in the cases.

Of 1826 patients on dialysis, 425 underwent gadolinium-enhanced MRI during the six-year study period. Since some patients underwent multiple studies, a total of 577 enhanced MR studies were performed, using Omniscan in most cases.

Thirteen dialysis patients who underwent gadolinium-enhanced MRI later developed NSF. Most cases were biopsy-proven. Non-NSF patients received a median dose of 30 mL, compared with 40 mL for NSF patients.

"We found a significant association with gadolinium-enhanced MRI exposure and NSF, as well as a significant association between dose of gadolinium and NSF. Multiple doses were given more often to the NSF group than to the non-NSF group," Roditi said.

Echoing advice of European authorities, the Scottish researchers advise cautious use of gadolinium contrast in patients with end-stage renal disease.

Aside from the 13 patients known to have been exposed to gadolinium, an additional patient developed NSF absent a gadolinium-enhanced study, suggesting that other factors aside from gadolinium contrast may play a role in triggering the disease.

Thirteen of the patients who developed NSF had received the Omniscan agent. Researchers calculated that NSF occurred in 0.77% of the total population of dialysis patients and 3.1% of dialysis patients who received an enhanced scan. Six of the 14 NSF patients died.

On average, it took 76 days for NSF to develop and be diagnosed, but the time period varied dramatically, with the longest time to diagnosis at almost 2400 days.

Tthe one case of a patient who developed NSF with no exposure and the long delay raise questions about whether other factors might have been involved in causing the skin condition, Roditi said.