What is the pathophysiology of nephrogenic systemic fibrosis (NSF)?

Updated: Sep 18, 2020
  • Author: Shawn Cowper, MD; Chief Editor: Dirk M Elston, MD  more...
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The pathophysiology of nephrogenic systemic fibrosis is related to the exposure of patients with renal insufficiency to gadolinium in association with imaging studies. The chelated forms of the less stable gadolinium chelates might have a significant role, but it appears that dissociated gadolinium's gradual release is pivotal in the development of nephrogenic systemic fibrosis and its sometimes delayed onset. [9]

Evidence for a link between nephrogenic systemic fibrosis and gadolinium was first described in a case series of 13 patients, all of whom developed nephrogenic systemic fibrosis after being exposed to gadolinium. [4] The mechanism by which this occurs in not known, but it seems to involve a cell termed a circulating fibrocyte that is stimulated by gadolinium. [10] Endothelin-1/endothelin receptor signaling plays a role in the calcification and fibrosis of nephrogenic systemic fibrosis. [11]

Toll-like receptors (TLR), in particular TLR4 and TLR7, play a role in the development of nephrogenic systemic fibrosis. [12]

Thomsen et al [13] noted that more than 90% of proven nephrogenic systemic fibrosis cases are related to gadodiamide (Omniscan) and some to gadopentetate (Magnevist). [14] As such, gadoversetamide (OptiMARK) and gadopentetate dimeglumine (Magnevist) should not be used for imaging in patients with renal impairment. MultiHance and ProHance, similar brands, should also likely not be used.

The safety of gadopentetate linear product might be no different from macrocyclic preparations such as gadodiamide (Omniscan), but guidelines should be followed in all gadolinium products. [15]

The macrocyclic contrast agents gadobutrol (Gadovist/Gadavist) and gadobenate dimeglumine (MultiHance) should be used only following guidelines. It is possible that Gadovist, Dotarem, and Prohance are safer, but this does not justify changing guidelines. [16]

While evidence data showing a benefit for prompt hemodialysis after gadolinium imaging are lacking, this is a justified precaution. Similar guidelines from the FDA and the American College of Radiology (ACR) state that gadolinium use with an approximate glomerular filtration rate of 30-44 mL/min per 1.73 m2 should be used with extreme caution.

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