Transmetallation and gadolinium: do low iron stores prevent the development of nephrogenic systemic fibrosis in high-risk end-stage renal disease patients?

Nephrogenic systemic fibrosis (NSF) is a systemic disorder that occurs in patients with renal failure and manifests as a thickening of the skin and flexion contractures of the joints. The etiology may involve an exposure to a gadolinium (Gd)-based magnetic resonance contrast agent. It has been proposed that in hemodialysis (HD) patients, iron mobilization (decreased total iron-binding capacity, increased iron level, and transferrin oversaturation) causes a transmetallation reaction and the release of free Gd from its chelator with the deposition of both Gd and iron in the affected tissues leading to fibrosis. The objective of this study was to investigate whether the use of gadopentetate dimeglumine leads to iron mobilization and to the development of NSF in HD patients. A retrospective chart analysis of 236 HD patients was performed and patients who had received a Gd-containing contrast agent were selected for analysis of their iron studies before and after the Gd exposure. A total of 25 patients were identified as having had a magnetic resonance imaging study and all were administered gadopentetate dimeglumine and no patients had any signs or symptoms suggestive of NSF. Six patients had the appropriate iron studies, which showed no statistically significant difference in the serum iron, total iron-binding capacity, ferritin, or transferrin saturation before and after exposure to gadopentetate dimeglumine. Our data suggest that the use of gadopentetate dimeglumine in HD patients did not cause iron mobilization and transmetallation therefore may partially explain the lack of development of NSF seen in our patient population.