[Nephrogenic systemic fibrosis]

Area of Science:

• Nephrology
• Radiology
• Toxicology

Context:

• Gadolinium-based contrast agents (GBCs) are widely used in magnetic resonance imaging (MRI).
• Nephrogenic systemic fibrosis (NSF) is a severe fibrotic disease linked to GBCs, primarily in patients with renal insufficiency (eGFR < 30ml/min/1.73 m2).
• The FDA approval of gadofosveset trisodium for MRA prompted a review of GBC-related adverse events.

Purpose:

• To review the rare, serious adverse reaction of NSF possibly related to gadolinium-based contrast agents.
• To discuss the proposed pathophysiologic mechanisms of NSF.
• To highlight the importance of risk assessment and dose reduction in patients with renal insufficiency.

Summary:

• NSF is characterized by skin thickening and hardening, potentially involving systemic organs, and is strongly associated with renal impairment.
• The exact mechanism involves the release of free gadolinium ions (Gd3+) from chelates, triggering fibrotic cascades involving macrophages and growth factors like TGF-beta.
• Linear, non-ionic GBCs like gadodiamide and gadopentetate dimeglumine have been most frequently implicated, while macrocyclic agents are rarely associated with NSF. Gadofosveset trisodium, despite its linear structure, has not been linked to NSF, possibly due to lower required doses.

Impact:

• Emphasizes the critical need to avoid GBCs in patients with renal insufficiency unless absolutely necessary.
• Underscores the importance of a thorough risk-benefit assessment and using the lowest effective dose when GBC administration is unavoidable.
• Highlights the ongoing need for research into GBC safety and NSF pathogenesis.