How Gadolinium-Based Contrast Agents Cause NSF

It is beyond dispute that gadolinium-based contrast agents cause nephrogenic systemic fibrosis (NSF).  The consensus in the medical and scientific community on how NSF is caused has been referred to as the "free gadolinium" theory.

The "Free Gadolinium" Theory on How Gadolinium-Based Contrast Agents Cause NSF

What has become known as the "free gadolinium" theory is that "dechelated" gadolinium  --  gadolinium that has become separated from the other chemical compounds that compose the gadolinium-based contrast agent  --  causes NSF.  Dialysis patients are most at risk of developing NSF because they are unable to excrete gadolinium-based contrast agents (GBCAs) from their bodies before they begin breaking down.

It has long been known that gadolinium in its pure, free state is highly toxic to human tissue.  In its free state, gadolinium reacts with human tissue, causing great harm.  The design of gadolinium-based contrast agents (GBCAs) is an effort to avoid this danger and make injection of gadolinium into the human body safe.  GBCA manufacturers attempted to alleviate the danger by "chelating" the gadolinium, meaning binding the gadolinium to an organic compound called a ligand.  The hope was that this chelation process would render the gadolinium inert (not harmful to human tissue) until it was eliminated from the human body through urination.

Unstable Gadolinium Contrast Agents Break Down Quicker, Causing NSF

However, most GBCAs are not stable, so sooner or later, the gadolinium becomes "dechelated" or "dissociated" from the ligand to which it was bound, and the toxic free gadolinium begins circulating throughout the human body.  Human tissues are exposed to the toxic gadolinium, and the gadolinium bonds to other compounds in the human body, beginning the fibrotic process that leads to NSF.  Because dialysis patients and other renally impaired persons are unable to remove gadolinium-based contrast agents from their bodies before dechelation begins, they are most at risk of developing NSF.  In turn, the three least stable gadolinium-based contrast agents  --  omniscan, magnevist and optimark  --  are most likely to cause NSF in people with kidney problems because dechelation begins much quicker than it does in other brands of GBCAs.