Possible involvement of gadolinium chelates in the pathophysiology of nephrogenic systemic fibrosis: A critical review

Idée, Jean‐Marc; Port, Marc; Medina, Christelle; Lancelot, Eric; Fayoux, Emmanuelle; Ballet, Sébastien; Corot, Claire

doi:10.1016/j.tox.2008.03.012

Cited by 140 publications

(82 citation statements)

References 104 publications

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“…A strong association has been demonstrated between exposure to each of several GBCAs and the onset of NSF (7,11,(15)(16)(17)(18)(19). At our institution, all patients who have developed NSF have had renal impairment and previous exposure to GBCAs.…”

Section: Discussionmentioning

confidence: 72%

Retrospective assessment of prevalence of nephrogenic systemic fibrosis (NSF) after implementation of a new guideline for the use of gadobenate dimeglumine as a sole contrast agent for magnetic resonance examination in renally impaired patients

Abujudeh

Rolls

Kaewlai

et al. 2009

Magnetic Resonance Imaging

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Stage 3-5 chronic kidney disease (CKD) undergoing gadobenate dimeglumine (GBD)-enhanced magnetic resonance (MR) examinations were included in the retrospective investigation. The electronic medical records were reviewed to assess the prevalence of nephrogenic systemic fibrosis (NSF) in renally impaired patients underwent GBDenhanced MR examinations. In all, 250 patients (98 men, mean age 72.6 years) were included: 97% of the patients had Stage 3 CKD (estimated GFR 30-59 mL/min/ 1.73 m 2 ); 37% had been exclusively exposed to GBD. The remaining were exposed to GBD and other gadoliniumbased contrast agents (GBCAs). The mean dose of GBD was 22 mL (standard deviation [SD], 11.2). Including exposure to other GBCAs, the mean cumulative dose of gadolinium was 61 mL (SD, 62.3). A total of 206 patients (82%) had skin examinations following the last GBD administration (mean duration, 108 days). No evidence of suspected or diagnosed NSF was found. In conclusion, on the basis of a retrospective chart review there was no skin evidence of NSF in predominantly Stage 3 CKD patients who were exposed to GBD at an average followup of 108 days, either solely or in combination with other GBCAs.

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Section: Discussionmentioning

confidence: 72%

Retrospective assessment of prevalence of nephrogenic systemic fibrosis (NSF) after implementation of a new guideline for the use of gadobenate dimeglumine as a sole contrast agent for magnetic resonance examination in renally impaired patients

Abujudeh

Rolls

Kaewlai

et al. 2009

Magnetic Resonance Imaging

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“…Both the high number of unpaired electrons of Gd 3þ (seven) in its 4f orbitals and very slow electronic relaxation rate explain its considerable paramagnetic behavior. However, because of its intrinsic (both acute and subacute) toxicity (11), gadolinium needs to be tightly chelated by an appropriate molecular ''scaffold-like structure'' (ie, the ligand) in order to be injected. It is commonly acknowledged that both the unchelated metal and free ligands are generally more toxic than the chelate itself (3).…”

Section: Chemistry and Pharmacology Of Gadolinium Chelatesmentioning

confidence: 99%

“…The technique used in these studies cannot formally discriminate between chelated and free gadolinium. However, it is very unlikely that a water soluble GC would persist in tissues for such a long time after administration, and especially after processing of the samples in aggressive organic solvents (11,45). In one study, all gadolinium deposits contained phosphorus, calcium, and sodium (45).…”

Section: Chemical Structure-thermodynamic Stability Relationshipmentioning

confidence: 99%

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Role of thermodynamic and kinetic parameters in gadolinium chelate stability

Idée

Port

Robic

et al. 2009

Magnetic Resonance Imaging

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162

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In recent years there has been a renewed interest in the physicochemical properties of gadolinium chelates (GC). The aim of this review is to discuss the physicochemical properties of marketed GC with regard to possible biological consequences. GC can be classified according to three key molecular features: 1) the nature of the chelating moiety: either macrocyclic molecules in which Gd 3þ is caged in the preorganized cavity of the ligand, or linear, openchain molecules; 2) ionicity: the ionicity of the molecule varies from neutral to tri-anionic agents; and 3) the presence or absence of an aromatic lipophilic moiety, which has a profound impact on the biodistribution of the GC. These parameters can also explain why GC differ considerably with regard to their thermodynamic stability constants and kinetic stability, as demonstrated by numerous studies. The concept of thermodynamic and kinetic stability is critically discussed, as it remains somewhat controversial, especially in predicting the amount of free gadolinium that may result from decomplexation of chelates in physiologic or pathologic situations. This review examines the possibility that the high kinetic stability provided by the macrocyclic structure combined with a high thermodynamic stability (reinforced by ionicity for macrocyclic chelates) can minimize the amount of free Gd 3þ released in the body.

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“…The Gd 3+ ions can be re leased through dechelation of less sta ble Gd che lates. This may bring about nephrogenic sys temic fi brosis in pa tients with kid ney fail ure or in suf fi ciency (Idée et al, 2008) and dis tur bance of cal cium ho meo sta sis in the or gan ism (Ku laksÏz and Bau, 2011).…”

Section: Introductionmentioning

confidence: 99%

The use of gadolinium and europium concentrations as contaminant tracers in the Nida River watershed in south-central Poland

Migaszewski

Gałuszka

2015

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1 Jan Kochanowski Uni ver sity, Fac ulty of Math e mat ics and Nat u ral Sci ences, OEwiêtokrzyska 15G, 25-406 Kielce, Po land Migaszewski, Z.M., Ga³uszka, A., 2016. The use of gad o lin ium and eu ro pium con cen tra tions as con tam i nant trac ers in the Nida River wa ter shed in south-cen tral Po land. Geo log i cal Quar terly, 60 (1): 67-76, doi: 10.7306/gq.1241 This pa per pres ents the re sults of rare earth el e ment (REE) de ter mi na tions in the Nowiny wastewater treat ment plant (NWWTP) effluents and Nida River sys tem wa ters of the south east ern Kielce Re gion (south-cen tral Po land). Of the REE exam ined, gad o lin ium and eu ro pium turned out to be very use ful for pin point ing anthropogenic and geogenic sources. Anthropogenic gad o lin ium (Gd anth ), used as a con trast ing agent in mag netic res o nance im ag ing (MRI), is re leased from the NWWTP into the river drain age sys tem. This micropollutant is traced down stream over the dis tance of about 15 km. This river stretch is char ac ter ized by a strong pos i tive NASC-nor mal ized Gd anth anom aly with the Gd NASC /Gd NASC * ra tio above 1.1 (1.80-15.57) and the Gd anth in put vary ing from 44 to 94%. Two ad di tional pos i tive Gd anth anom a lies re corded in the rivers Bobrza and Nida point out to mix ing of effluents de rived from the NWWTP and other lo cal wastewater treat ment plants. In con trast, the Gd anth -un con tam i nated wa ters up stream, or down stream far away from the NWWTP dis play a dis tinct pos i tive NASC-nor mal ized Eu anom aly high lighted by a high Eu/Eu* ra tio in the range of 2.87 to 29.70. The lack of Gd anth anom aly upstream from the NWWTP also in di cates that there is no leak age of mu nic i pal sew age from the san i tary col lec tor sewer into the Silnica River. Thus Gd as a con tam i nant may be ef fec tively used as a tracer in sim i lar pol lu tion stud ies be cause it is rel atively sim ple and cost-ef fec tive to dis crim i nate be tween con tam i nant con cen tra tions and nor mal back ground con cen tra tions. Key words: rare earth el e ments, wastewater ef flu ent, Nida River drain age sys tem, anthropogenic gad o lin ium, geogenic euro pium.

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Possible involvement of gadolinium chelates in the pathophysiology of nephrogenic systemic fibrosis: A critical review

Cited by 140 publications

References 104 publications

Retrospective assessment of prevalence of nephrogenic systemic fibrosis (NSF) after implementation of a new guideline for the use of gadobenate dimeglumine as a sole contrast agent for magnetic resonance examination in renally impaired patients

Retrospective assessment of prevalence of nephrogenic systemic fibrosis (NSF) after implementation of a new guideline for the use of gadobenate dimeglumine as a sole contrast agent for magnetic resonance examination in renally impaired patients

Role of thermodynamic and kinetic parameters in gadolinium chelate stability

The use of gadolinium and europium concentrations as contaminant tracers in the Nida River watershed in south-central Poland

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