The nephrological department of Copenhagen University Hospital Herlev experienced an epidemic accumulation of patients developing
nephrogenic systemic fibrosis in the period 2002-2006. Systematic studies of these patients revealed that they all had a
gadodiamide-enhanced magnetic resonance examination prior to their symptoms, and that they all had severe
renal insufficiency (chronic kidney disease stage 5) at the time of their exposure to
gadodiamide. Besides exposure to
gadodiamide, our analyses indicated that increasing cumulative
gadodiamide exposure (i.e. repeated exposures), and higher serum concentrations of ionized
calcium and
phosphate were cofactors that raised the risk of developing
nephrogenic systemic fibrosis. Higher cumulative
gadodiamide exposure, higher prescribed
erythropoietin dosage at exposure, and being
hemodialysis patient were three factors associated with
nephrogenic systemic fibrosis in its most severe form. Retrospective reviews of patients records and patient interviews revealed the large variability in symptoms and
clinical course of
nephrogenic systemic fibrosis, but also highlighted that the typical initial symptoms were symmetric swelling, discoloration and
pain of lower legs, whereas the typical late symptoms of severely affected patients were skin thickening, stiffness,
contractures, and debilitating disabilities. In conclusion,
nephrogenic systemic fibrosis is a serious
iatrogenic disease of patients with
renal insufficiency caused by some Gd-containing
contrast agents, in particular
gadodiamide. Unfortunately, there is no proven curative treatment. It is therefore essential that future cases of
nephrogenic systemic fibrosis are prevented.