Experimental studies investigating the pathophysiology of nephrogenic systemic fibrosis; what did we learn so far?

Excerpt

The association between nephrogenic systemic fibrosis (NSF) and gadolinium based contrast agents (Gd-CAs) was first suggested in 2006 [1, 2]. This was followed by several reports confirming this association with the vast majority of published cases were associated with the non-ionic linear agent gadodiamide “Gd-DTPA-BMA” (Omniscan, GE Healthcare, USA) [3]. Smaller percentages of cases have been directly linked to the ionic linear chelate gadopentate dimeglumine “Gd-DTPA” (Magnevist, Bayer-Schering, Germany), and the non-ionic linear chelate gadoversetamide “Gd-DTPA-BMEA” (OptiMARK, Covidien, USA) [3]. The high temporal association with the administration of Omniscan which has low kinetic and thermodynamic stability raised the possibility that NSF is caused by the release of toxic Gd ions from unstable Gd-CA molecules [4]. This probable explanation promoted extensive investigation of the importance of stability of Gd-CAs in the pathogenesis of NSF with several experimental studies had been published in the literature over the last few years. The extent to which these studies increased the understanding of the pathophysiology of NSF is the main focus of this editorial. Concise summary of key studies in this field will be presented including those evaluating the stability of Gd-CAs and their biological effects, in vivo and in vitro. …