Involvement of Gadolinium Chelates in the Mechanism of Nephrogenic Systemic Fibrosis: An Update

Nephrogenic systemic fibrosis (NSF) is a highly debilitating scleroderma-like disease occurring exclusively in patients with severe or end-stage renal failure. Since the recognition of a link between gadolinium chelates (GCs) used as contrast agents for MR imaging and NSF by two independent European teams in 2006, numerous studies have described the clinical issues and investigated the mechanism of this disease. So far the most commonly reported hypothesis is based on the in vivo dechelation of GCs. The physicochemical properties of GCs, especially their thermodynamic and kinetic stabilities, are described in the present article. High kinetic stability provided by the macrocyclic structure, combined with high thermodynamic stability, minimizes the amount of free gadolinium released in the body. The current hypotheses regarding the pathophysiologic mechanism are critically discussed.