Modern Gadolinium Contrast Agents Pose Minimal NSF Risk, Large Study Suggests

Gadolinium-based contrast agents (GBCAs) have long been linked to a rare but serious condition known as nephrogenic systemic fibrosis (NSF), especially in patients with advanced kidney disease. But new research suggests the risk of developing NSF from modern GBCAs is now “exceedingly low,” even among the most vulnerable patients.

NSF, first recognized in the early 2000s, is a potentially life-threatening disorder that causes skin thickening, joint contractures and internal organ fibrosis. The condition was strongly associated with GBCA use in patients with severe renal impairment, prompting the U.S. Food and Drug Administration to issue safety warnings and driving the development of newer, safer contrast agents.

Today’s GBCAs include Group 2 agents such as gadobenate (MultiHance), gadobutrol (Gadavist) and gadoterate (Dotarem), which are considered to have a much lower risk profile than older linear agents. Regulatory oversight and improved clinical screening have also contributed to a dramatic decline in NSF cases. Still, researchers have remained cautious, questioning whether some cases go unreported or are misdiagnosed.

To better understand the lingering risk, researchers from Virginia Commonwealth University, led by Cory Trankle, MD, conducted a large-scale analysis using real-world clinical data. They reviewed records from the TriNetX U.S. Network, focusing on adults with stage 4 or 5 chronic kidney disease (CKD) or end-stage renal disease (ESRD) who underwent MRI scans with gadolinium contrast between 2010 and 2025. Their goal was to determine whether any patients were diagnosed with NSF within one year of contrast administration and to assess whether any patient factors might explain such a diagnosis.

The results were reassuring. Out of more than 73,000 patients with advanced renal dysfunction, only 36 (0.05%) were diagnosed with possible NSF. Among patients with ESRD, the number was slightly higher—542 patients (0.74%)—but nearly identical to the rate observed in a control group of individuals without kidney disease, where 518 (0.71%) were diagnosed with a similar condition. These figures were consistent across all modern contrast agents.

Importantly, the researchers emphasized that this was a “worst-case scenario” analysis, accounting for any potential underreporting or misclassification. They believe their findings support the safety of Group 2 GBCAs in patients with renal impairment and may also point to a need for improved diagnostic accuracy around NSF.

“Although there has been a dramatic reduction in suspected NSF cases, it is possible that cases have been diagnosed but not reported or NSF has been misdiagnosed as another condition,” the authors noted. “The aim of this study was to examine whether there might still be—and if so, the magnitude of—residual risk of NSF with contemporary GBCAs in patients with advanced renal dysfunction.”

Ultimately, the findings bolster confidence in the safety profile of today’s GBCAs and may help reduce hesitation around using contrast-enhanced imaging in patients with kidney disease. While continued vigilance is necessary, the data underscore just how far the field has come in mitigating one of its most serious risks.