Wednesday, April 17, 2019

Topic Discussion: Newer Gadolinium agents and risk of NSF? is it extinct?

Gadolinium is known to have an association with Nephrogenic Systemic Fibrosis(NSF). The first case of this was described in Yale and published in Lancet. A potential link between NSF and the application of gadolinium-based contrast agents (GBCAs) was first described by Grobner et al in 2006. The risk of gadolinium based contrast agents to trigger NSF seems to be related to the stability of the agent. Thus, nonionic linear gadolinium based contrast agents are more likely to trigger NSF than ionic linear agents both of which are distinctly more likely to trigger the disease than the macrocyclic agents in patients with reduced renal function. Gadobutrol (Gadovist, Gadavist) is a second-generation nonionic, multipurpose, extracellular, macrocyclic gadolinium based contrast agent provided in a 1 molar concentration. As a macrocyclic contrast agent, gadobutrol provides high chelate stability with substantially less—if any—in vivo release of Gd ions as opposed to linear gadolinium (old school agents). The release of gadolinium ions has been linked to an increased risk of NSF in patients with impaired renal function. The highest prevalence of NSF was associated with Omniscan, Optimark as most of these have a weak binding of gadolinium to the chelate. 

Image result for new gadolinium agents and NSF

So are these safer? A large study published in 2017 was a prospective, international, multicenter, open-label study in 55 centers. Patients with moderate to severe renal impairment scheduled for any gadobutrol-enhanced MRI were included. All patients received a single intravenous bolus injection of gadobutrol at a dose of 0.1 mmol/kg body weight. The primary target variable was the number of patients who develop NSF within a 2-year follow-up period. A total of 908 patients were enrolled, including 586 with moderate and 284 with severe renal impairment who are at highest risk for developing NSF. Overall, 184 patients (20.3%) underwent further contrast-enhanced MRI with other gadolinium-based contrast agents within the 2-year follow-up. No patient developed symptoms conclusive of NSF.

Another study by Lauenstein et al, investigated gadoxetate disodium in 357 patients. No case of NSF was recorded. Another recent study by Amet et al investigated the risk of gadoteric acid in 255 patients on dialysis with no findings of NSF. In addition, Soulez et al reported 2 prospective 2-year studies in 534 patients with either stage 3 chronic kidney disease (CKD) or stage 4 to 5 CKD. No signs or symptoms of NSF were reported after administration of gadobenate dimeglumine or gadoteridol. Smorodinsky et al retrospectively evaluated 1167 patients with chronic liver disease where 72% also had some degree of renal insufficiency. They did not report any case of NSF.

A recent Canadian society published their analysis and concluded that “In patients with AKI and category G4 and G5 CKD (eGFR < 30 mL/min/1.73 m2) and in dialysis-dependent patients who require Gadolinium based contrast agentss-enhanced MRI, they can be administered with exceedingly low risk of causing NSF when using macrocyclic agents and newer linear agents at routine doses.”

Here are images online from medscape education that are very useful on this matter.

A lot of centers in the world are now carrying and using Gadovist and perhaps we won’t see any NSF? 

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