The role of gadolinium chelates in the mechanism of nephrogenic systemic fibrosis: A critical update

Crit Rev Toxicol. 2014 Nov;44(10):895-913. doi: 10.3109/10408444.2014.955568. Epub 2014 Sep 26.


Nephrogenic systemic fibrosis (NSF) is an iatrogenic scleroderma-like fibrosing systemic disorder occurring in patients with severe or end-stage renal disease. It was established as a new clinical entity in the year 2000. A causal role for gadolinium chelates (GC), widely used as contrast agents for magnetic resonance imaging, was suggested six years later. It rapidly appeared that the occurrence of NSF was associated with prior administration of GCs with lower thermodynamic stability, leading to warnings being published by health authorities and learned societies worldwide. Although a role for the chelated form of the less stable GCs has been proposed, the most commonly accepted hypothesis involves the gradual release of dissociated gadolinium in the body, leading to systemic fibrosis. However, the entire chain of events is still not fully understood in a causal way and many uncertainties remain.

Keywords: circulating fibrocytes; contrast agents; fibroblasts; gadolinium; gadolinium chelates; kidney diseases; magnetic resonance imaging; nephrogenic systemic fibrosis; transmetallation.

Publication types

  • Review

MeSH terms

  • Animals
  • Chelating Agents / chemistry
  • Contrast Media / chemistry
  • Disease Models, Animal
  • Fibrosis
  • Gadolinium / chemistry
  • Gadolinium / toxicity*
  • Humans
  • Magnetic Resonance Imaging
  • Nephrogenic Fibrosing Dermopathy / chemically induced
  • Nephrogenic Fibrosing Dermopathy / pathology*
  • Risk Factors


  • Chelating Agents
  • Contrast Media
  • Gadolinium