Meta-analysis reveals a strong association between contrast agents and nephrogenic systemic fibrosis.

Evidence suggests a potentially causal link between gadolinium-based contrast agents (GBCAs) and nephrogenic systemic fibrosis (NSF) in patients with advanced kidney disease, according to researchers.

Rajender Agarwal, MD, and colleagues at the University of Pennsylvania in Philadelphia performed a systemic review and meta-analysis of controlled studies that have examined the association between GBCAs and NSF. The researchers extracted and analyzed data from seven studies.

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In four of these, gadodiamide was the sole or predominant GBCA; one study focused only on gadopentetate; and the other studies did not specify the agents that were administered.

Among patients with advanced kidney disease, NSF was 27 times more likely to develop in patients exposed to gadolinium than in those not exposed these agents, researchers reported in Nephrology Dialysis Transplantation (2009;24:856-863).

According to the researchers, evidence supporting a causal relationship includes the following: a significant association demonstrated in six of the seven studies; consistently similar results and large magnitude of effect shown in all studies; a clear temporal relationship found in all but one study; and a dose-response relationship shown in three studies.

Two studies did not find this relationship and the other studies did not examine the relationship. In addition, gadodiamide is excreted renally, so it is biologically plausible for it to cause NSF, the investigators observed.

Furthermore, gadodiamide is both detectable and quantifiable in the tissues of patients with NSF. Dr. Agarwal’s group also cited a case in which a patient who had clinical resolution of NSF experienced NSF again when re-exposed to gadodiamide.

“Our analyses suggest a potent and significant association between GBCAs and NSF among patients with advanced CKD,” the authors concluded.