What causes nephrogenic systemic fibrosis (NSF)?

Updated: May 22, 2018
  • Author: Noah S Scheinfeld, JD, MD, FAAD; Chief Editor: Dirk M Elston, MD  more...
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The cause of nephrogenic systemic fibrosis is the connexation of renal insufficiency and gadolinium exposure from imaging studies. The exact degree of renal insufficiency that sets up the development of nephrogenic systemic fibrosis is not known. Risk factors include advanced chronic kidney disease (stages 4 and 5) and acute or chronic inflammatory insults. The US Food and Drug Administration (FDA) has updated its public health advisory to include patients with moderate renal insufficiency (chronic kidney disease stage 3). [30] Metformin use might influence nephrogenic systemic fibrosis, but this is not proven. [23]

Gadolinium-based contrast agents (Ablavar, Eovist, Magnevist, MultiHance, Omniscan, OptiMARK, ProHance) have recently been linked to the development of nephrogenic systemic fibrosis. The disease has occurred in patients with moderate- to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or magnetic resonance angiography. As of late December 2006, the FDA had received reports of 90 such cases. Worldwide, the FDA has reported more than 200 cases.

On September 9, 2010, the FDA announced it is requiring that gadolinium-based contrast agents (GBCAs) carry new warnings on their labels about the risk for nephrogenic systemic fibrosis and its association when administered to certain patients with kidney disease. The FDA's review of the safety of the most widely used GBCAs determined that Magnevist, Omniscan, and Optimark are associated with a greater risk for nephrogenic systemic fibrosis than other GBCAs. These 3 agents will be contraindicated for use in certain patients with kidney disease, while other gadolinium contrast agents will carry a warning. Data suggest that nephrogenic systemic fibrosis may follow the administration of any GBCA, and the FDA continues to assess the safety of each GBCA to better estimate its nephrogenic systemic fibrosis risks. [31]

Nephrogenic systemic fibrosis is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness.

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