Type of MRI contrast, tissue gadolinium, and fibrosis

Am J Physiol Renal Physiol. 2014 Oct 1;307(7):F844-55. doi: 10.1152/ajprenal.00379.2014. Epub 2014 Aug 6.


It has been presupposed that the thermodynamic stability constant (K(therm)) of gadolinium-based MRI chelates relate to the risk of precipitating nephrogenic systemic fibrosis. The present study compared low-K(therm) gadodiamide with high-K(therm) gadoteridol in cultured fibroblasts and rats with uninephrectomies. Gadolinium content was assessed using scanning electron microscopy equipped with energy-dispersive X-ray spectroscopy in paraffin-embedded tissues. In vitro, fibroblasts demonstrated dose-dependent fibronectin generation, transforming growth factor-β production, and expression of activated myofibroblast stress fiber protein α-smooth muscle actin. There were negligible differences with respect to toxicity or proliferation between the two contrast agents. In the rodent model, gadodiamide treatment led to greater skin fibrosis and dermal cellularity than gadoteridol. In the kidney, both contrast agents led to proximal tubule vacuolization and increased fibronectin accumulation. Despite large detectable gadolinium signals in the spleen, skin, muscle, and liver from the gadodiamide-treated group, contrast-induced fibrosis appeared to be limited to the skin and kidney. These findings support the hypothesis that low-K(therm) chelates have a greater propensity to elicit nephrogenic systemic fibrosis and demonstrate that certain tissues are resistant to these effects.

Keywords: animals; fibrosis; gadolinium/adverse effects; magnetic resonance imaging/adverse effects; nephrogenic fibrosing dermopathy; skin diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Contrast Media / adverse effects*
  • Contrast Media / chemistry
  • Female
  • Fibroblasts / metabolism
  • Fibronectins / metabolism
  • Gadolinium / adverse effects
  • Gadolinium / chemistry
  • Gadolinium DTPA / adverse effects*
  • Gadolinium DTPA / chemistry
  • Heterocyclic Compounds / adverse effects*
  • Heterocyclic Compounds / chemistry
  • Humans
  • Magnetic Resonance Imaging
  • Nephrogenic Fibrosing Dermopathy / chemically induced*
  • Nephrogenic Fibrosing Dermopathy / metabolism
  • Organometallic Compounds / adverse effects*
  • Organometallic Compounds / chemistry
  • Rats, Inbred F344
  • Renal Insufficiency / complications
  • Thermodynamics


  • Contrast Media
  • Fibronectins
  • Heterocyclic Compounds
  • Organometallic Compounds
  • gadoteridol
  • gadodiamide
  • Gadolinium
  • Gadolinium DTPA