title: Mechanism of NSF: New evidence challenging the prevailing theory.
abstract: Nephrogenic systemic fibrosis (NSF) has been associated with the administration of gadolinium-based contrast agents in patients with severely impaired renal function (SIRF), endstage renal disease (ESRD), or acute renal failure (ARF). Since the vast majority of these patients do not get NSF, it is highly likely that patient factors play a role in its development. Although "free" or dechelated gadolinium is thought by some to be the only trigger of NSF, recent evidence suggests that chelated gadolinium may be important. Chelated gadolinium such as Omniscan (gadodiamide) and Magnevist (gadopentetate) can directly stimulate macrophages and monocytes in vitro to release profibrotic cytokines and growth factors capable of initiating and supporting the tissue fibrosis that is characteristic of NSF. In addition, an effect of chelated gadolinium on fibroblasts has also been demonstrated. Chelated gadolinium in the form of Omniscan, Magnevist, MultiHance, and ProHance increased proliferation of human dermal fibroblasts. Indeed, increased numbers of macrophages, together with activated fibroblasts and fibrocytes, are essential cells in the fibrotic process and are present in NSF skin. Accordingly, it is important that chelated gadolinium, in combination with patient cofactors, is considered in the etiology of NSF associated with enhanced scans. J. Magn. Reson. Imaging 2009;30:1277-1283. (c) 2009 Wiley-Liss, Inc.
authors: GE Healthcare, Medical Diagnostics Discovery Research, Amersham, UK. ben.newton@ge.com
authors: Ben B
authors: BB
authors: Newton
authors: Sergio A
authors: SA
authors: Jimenez
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000009:adverse effects*; D005682:Gadolinium / Q000009:adverse effects*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000009:adverse effects*; D008954:Models, Biological; D054989:Nephrogenic Fibrosing Dermopathy / Q000139:chemically induced* / Q000503:physiopathology*
chemical_list: D003287:Contrast Media; D005682:Gadolinium