Risk Factors for Developing Gadolinium-Induced Nephrogenic Systemic Fibrosis

Abstract

Objective: To identify medications and other potential risk factors, in addition to renal dysfunction, for developing gadolinium-induced nephrogenic systemic fibrosis (NSF). Data Sources: Information was obtained from PubMed, International Pharmaceutical Abstracts, Iowa Drug Information Service, and Google Scholar, using the unlimited search terms nephrogenic systemic fibrosis, NSF, nephrogenic fibrosing dermopathy, NFD, gadolinium, gadodiamide, gadoversetamide, gadopentetate, gadobenate, and gadoteridol. Information was also obtained from the Food and Drug Administration, as well as the manufacturers of the above-mentioned products. Data were collected during April and May 2007. Study Selection and Data Extraction: All identified articles and information were evaluated. Articles and other information that included data regarding concurrent medications, disease states, and other risk factors for developing gadolinium-induced NSF were included in this review, as were clinical practice guidelines. Data Synthesis: NSF is a mysterious and severe disorder that occurs in individuals with severe renal impairment. Virtually all cases of NSF have been associated with the administration of gadolinium-containing contrast media. However, not all renally impaired patients who receive gadolinium develop NSF. Thus, additional risk factors for the development of NSF have been suggested. These risk factors include medications that could cause transmetallation of gadolinium, medications that could cause acidosis, and high doses of erythropoietin. Concomitant medical conditions, including hyperphosphatemia, acidosis, recent surgery, hepatic disease, hypercoagulability, and proinflammatory processes may also predispose patients to NSF. Conclusions: Gadolinium-based contrast agents should be avoided in patients with significant renal impairment unless the benefits clearly outweigh the risks. If gadolinium is required, nonionic linear chelates (eg, gadodiamide, gadoversetamide) should not be used. Renally impaired individuals who require gadolinium should be screened proactively for underlying disease states and concomitant drugs that may increase their risk of developing NSF; therapy should be adjusted accordingly.