Effect of Different Classes of Gadolinium-based Contrast Agents on Control and Nephrogenic Systemic Fibrosis–derived Fibroblast Proliferation

Semelka

American Journal of Neuroradiology

et al. 2015

373

244

SUMMARY:In current practice, gadolinium-based contrast agents have been considered safe when used at clinically recommended doses in patients without severe renal insufficiency. The causal relationship between gadolinium-based contrast agents and nephrogenic systemic fibrosis in patients with renal insufficiency resulted in new policies regarding the administration of these agents. After an effective screening of patients with renal disease by performing either unenhanced or reduced-dose-enhanced studies in these patients and by using the most stable contrast agents, nephrogenic systemic fibrosis has been largely eliminated since 2009. Evidence of in vivo gadolinium deposition in bone tissue in patients with normal renal function is well-established, but recent literature showing that gadolinium might also deposit in the brain in patients with intact blood-brain barriers caught many individuals in the imaging community by surprise. The purpose of this review was to summarize the literature on gadolinium-based contrast agents, tying together information on agent stability and animal and human studies, and to emphasize that low-stability agents are the ones most often associated with brain deposition.ABBREVIATIONS: DN ϭ dentate nuclei; GBCA ϭ gadolinium-based contrast agent; NSFϭ nephrogenic systemic fibrosis

Section: 45mentioning

confidence: 99%

Gadolinium-Based Contrast Agent Accumulation and Toxicity: An Update

Semelka

American Journal of Neuroradiology

et al. 2015

373

244

Clinical and Experimental Immunology

“…Recently, it has been reported that Omniscan stimulation of production of proinflammatory/profibrotic cytokines, chemokines and growth factors is mediated by Toll-like receptor (TLR)-4 and TLR-7 in normal differentiated human macrophages [19]. Numerous other studies have demonstrated that GdBCA can induce profibrotic responses in normal and NSF fibroblasts as well as in skin organ cultures [20][21][22][23]. However, the induction of a type I interferon (IFN) signature and a detailed comparison of proinflammatory and profibrotic effects of various linear and macrocyclic GdBCA have not been performed.…”

Section: Introductionmentioning

confidence: 99%

Induction of a type I interferon signature in normal human monocytes by gadolinium-based contrast agents: comparison of linear and macrocyclic agents

Wermuth

Jimenez

2013

SummaryThe gadolinium-based contrast agent (GdBCA) Omniscan activates human macrophages through Toll-like receptor (TLR)-4 and TLR-7 signalling. To explore the mechanisms responsible we compared the ability of linear and macrocyclic GdBCA to induce a type I interferon signature and a proinflammatory/profibrotic phenotype in normal human monocytes in vitro. Expression of genes associated with type I interferon signalling and inflammation and production of their corresponding proteins were determined. Both linear and macrocyclic GdBCA stimulated expression of multiple type I interferon-regulated genes and the expression of numerous chemokines, cytokines and growth factors in normal human peripheral blood monocytes. There was no correlation between the magnitude of the measured response and the Gd chelate used. To explore the mechanisms responsible for GdBCA induction of fibrosis in nephrogenic systemic fibrosis (NSF) in vitro, normal human dermal fibroblasts were incubated with GdBCA-treated monocyte culture supernatants and the effects on profibrotic gene expression were examined. Supernatants from monocytes exposed to all GdBCA stimulated types I and III collagen, fibronectin and α-smooth muscle actin (α-SMA) expression in normal dermal fibroblasts. The results indicate that the monocyte activation induced by GdBCA may be the initial step in the development of GdBCA associated fibrosis in NSF.

“…The prevalence of NSF after exposure to gadodiamide hydrate is up to 7% in patients who have reduced renal function [7]; however, NSF occurs infrequently because of recognition among radiologists and other experts of the association between GBCA administration and NSF [8]. All GBCAs carry a risk when used in high doses [9]. In accordance with the Joint Committee's guidelines [2], we use \0.1 mmol/kg of gadoteridol or \0.1 mmol/kg of meglumine gadoterate in patients in whom we have not evaluated eGFR.…”

Section: Discussionmentioning

confidence: 99%

Distribution of estimated glomerular filtration rate (eGFR) values in patients receiving contrast-enhanced magnetic resonance imaging

et al. 2011