Gadolinium and nephrogenic fibrosing dermopathy in pediatric patients

Dharnidharka, Vikas R.; Wesson, Stanton K.; Fennell, Robert S.

doi:10.1007/s00467-006-0384-z

Cited by 38 publications

(11 citation statements)

References 3 publications

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“…• Metabolic acidosis as a cofactor (Dharnidharka et al 2006). Due to their relatively rapid dechelation or transmetallation kinetics, it has been argued that linear open-chain gadolinium chelates could reach a thermodynamic equilibrium (in contrast with macrocyclic chelates characterized by high kinetic stability) and in that case conditional stability and selectivity could be important physicochemical criteria to predict the amount of gadolinium released (as shown by the plateau in Fig.…”

Section: Resultsmentioning

confidence: 98%

Efficiency, thermodynamic and kinetic stability of marketed gadolinium chelates and their possible clinical consequences: a critical review

et al. 2008

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Gadolinium-based contrast agents are widely used to enhance image contrast in magnetic resonance imaging (MRI) procedures. Over recent years, there has been a renewed interest in the physicochemical properties of gadolinium chelates used as contrast agents for MRI procedures, as it has been suggested that dechelation of these molecules could be involved in the mechanism of a recently described disease, namely nephrogenic systemic fibrosis (NSF). The aim of this paper is to discuss the structure-physicochemical properties relationships of marketed gadolinium chelates in regards to their biological consequences. Marketed gadolinium chelates can be classified according to key molecular design parameters: (a) nature of the chelating moiety: macrocyclic molecules in which Gd3+ is caged in the pre-organized cavity of the ligand, or linear open-chain molecules, (b) ionicity: the ionicity of the complex varies from neutral to tri-anionic agents, and (c) the presence or absence of an aromatic lipophilic residue responsible for protein binding. All these molecular characteristics have a profound impact on the physicochemical characteristics of the pharmaceutical solution such as osmolality, viscosity but also on their efficiency in relaxing water protons (relaxivity) and their biodistribution. These key molecular parameters can also explain why gadolinium chelates differ in terms of their thermodynamic stability constants and kinetic stability, as demonstrated by numerous in vitro and in vivo studies, resulting in various formulations of pharmaceutical solutions of marketed contrast agents. The concept of kinetic and thermodynamic stability is critically discussed as it remains a somewhat controversial topic, especially in predicting the amount of free gadolinium which may result from dechelation of chelates in physiological or pathological situations. A high kinetic stability provided by the macrocyclic structure combined with a high thermodynamic stability (reinforced by ionicity for macrocyclic chelates) will minimize the amount of free gadolinium released in tissue parenchymas.

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Section: Resultsmentioning

confidence: 98%

Efficiency, thermodynamic and kinetic stability of marketed gadolinium chelates and their possible clinical consequences: a critical review

et al. 2008

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“…Patients with hepatorenal syndrome and those undergoing liver transplantation seem to be at particular risk for developing GASF [ 13 , 17 , 18 ]. It has also been hypothesized that GASF may result from highdose erythropoietin [ 19 , 20 ] or sevelamer therapy [ 21 ], lack of treatment with angiotensin-converting enzyme inhibitors [ 22 ], or increased iron mobilization [ 23 ]. However, these theories have not been well substantiated and do not adequately account for the recent emergence of GASF as a distinct clinical entity.…”

Section: Clinical Presentationmentioning

confidence: 97%

Nephrogenic systemic fibrosis: An epidemic of gadolinium toxicity

Todd

Kay

2008

Curr Rheumatol Rep

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Nephrogenic systemic fibrosis is a devastating systemic fibrosing disorder that afflicts patients with renal dysfunction. Growing evidence supports the hypothesis that gadolinium-containing contrast agents (GCCAs) trigger the development of nephrogenic systemic fibrosis. Hence, this condition is most appropriately called gadolinium---associated systemic fibrosis (GASF). In this report, we review the history of GASF, its association with prior GCCA exposure, its clinicopathologic features, the relevant pharmacology of GCCAs, the likely role of GCCAs in its pathogenesis, and potential treatments.

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“…NSF has been reported in one 6-year-old patient and in older children after administration of the least stable linear agents to children with renal impairment (Dharnidharka et al 2007;Foss et al 2009;Jain et al 2004). Recent research on the prevalence of NSF in children identified 20 pediatric cases, 12 of which had documented gadolinium exposure (K. Darge, Personal communication).…”

Section: Gadolinium-based Contrast Mediamentioning

confidence: 95%

Contrast Media Use in Pediatrics: Safety Issues

Riccabona

2014

Medical Radiology

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Gadolinium and nephrogenic fibrosing dermopathy in pediatric patients

Cited by 38 publications

References 3 publications

Efficiency, thermodynamic and kinetic stability of marketed gadolinium chelates and their possible clinical consequences: a critical review

Efficiency, thermodynamic and kinetic stability of marketed gadolinium chelates and their possible clinical consequences: a critical review

Nephrogenic systemic fibrosis: An epidemic of gadolinium toxicity

Contrast Media Use in Pediatrics: Safety Issues

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