Nephrogenic Systemic Fibrosis: Is Gadolinium the Missing Piece to the Puzzle? (See Erratum 2008;82:158)
New medical disorders arise infrequently, but nephrogenic systemic fibrosis (NSF) is one such entity. It exclusively affects patients with renal failure, resulting in debilitating progressive fibrosis of the skin and systemic organs. Although much work has been done elucidating the histopathologic changes, a trigger has not been detected. Recently, case reports have implicated gadolinium (Gd) contrast agents as a potential etiology, prompting a health advisory from the US Food and Drug Administration (FDA) in June 2006. We discuss the literature regarding the effects of Gd on tissue and its potential relationship to the known histopathologic characteristics of NSF.
Although there appears to be a strong association between Gd exposure and NSF, potential triggers are still being evaluated. In the past decade, there has been a dramatic shift to the use of MRA with Gd contrast in patients with renal failure due to known contrast-induced nephropathy observed with iodinated contrast. Considering the number of patients with renal failure receiving Gd contrast, Gd exposure alone is unlikely to be the sole cause of NSF and is more likely a component in a multifactorial process; however, the other risk factors remain elusive. MRA technology has been lifesaving for many patients with renal failure and remains a medical necessity in many situations, but the possible link to NSF may result in a need to modify current medical practices. The FDA's public health advisory strongly recommends prompt initiation of dialysis in any patient with advanced kidney disease who undergoes MRA with Gd.16 With the potential association of the dissociation of Gd chelates in an acidic environment, it also may be prudent to consider normalizing the pH of patients with bicarbonate infusion prior to MRA. At this time, further studies evaluating the safety of Gd contrast, its possible link to NSF, and the possible role of macrophage inhibition in the pathophysiology of NSF are needed.
