Dermal inorganic gadolinium concentrations: evidence for in vivo transmetallation and long-term persistence in nephrogenic systemic fibrosis

Abraham, Jerrold L.; Thakral, Charu; Skov, Lone; Rossen, Kristian; Marckmann, Peter

doi:10.1111/j.1365-2133.2007.08335.x

Cited by 190 publications

(136 citation statements)

References 31 publications

(60 reference statements)

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“…In 10 patients repeated skin biopsies were performed and showed an increase over time in Gd deposits in those patients who received the first biopsy within the first 2 years after disease onset. The authors hypothesized that Gd may be mobilized over time from bone stores, explaining the variably delayed onset of NSF and increasing skin concentration over time (16). This position was shared by Thakral et al (60), who found high concentrations of gadolinium in a patient in serial biopsies performed over a period of 3 years.…”

Section: Onset Of Diseasementioning

confidence: 96%

“…In a series of 13 cases the median time was 25 days (14). In another series of 20 patients the disease onset after Gd-CA exposure ranged from 16 days to 1991 days (16). In 10 patients repeated skin biopsies were performed and showed an increase over time in Gd deposits in those patients who received the first biopsy within the first 2 years after disease onset.…”

Section: Onset Of Diseasementioning

confidence: 98%

“…In the published literature the onset of NSF after Gd-CA varies between a few days to several months (13,14,16,50,58,59). However, the exact time between Gd-CA exposure and the first sign of symptoms is difficult to ascertain because it depends on the patients' awareness and reporting.…”

Section: Onset Of Diseasementioning

confidence: 99%

“…As of February 2008, 190 biopsy-proven cases were identified in the peer-reviewed literature that confirmed an association of disease onset with exposure to Gd-CAs (Table 2) (15). Meanwhile, there is an increasing body of clinical and experimental data that show a significant link between Gd-CA and NSF in renal patients (16)(17)(18)(19)(20)(21). To emphasize the central role of Gd-CA, there are authors who now propose to call the disorder ''gadolinium-associated systemic fibrosis'' (GASF) (22).…”

mentioning

confidence: 99%

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Nephrogenic systemic fibrosis: Clinical spectrum of disease

Mayr

Burkhalter

Bongartz

2009

Magnetic Resonance Imaging

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Nephrogenic systemic fibrosis (NSF) is a rare systemic fibrosing disorder that primarily affects the skin and the subcutaneous structures. Also, there are reports of involvement of deeper structures and organs in the human body, but the confirmation of systemic involvement is complicated by overlap of other disease processes that occur in patients with severe renal impairment. The disorder leads to significant disability and is an important contributing factor of death. Virtually all patients who developed NSF suffered from endstage renal disease (ESRD) or severe chronic kidney disease (CKD) or from an acute acquired kidney injury (AKI). There is an increase in evidence that a causal relation between gadolinium‐based contrast agents (Gd‐CA) and NSF is probable. Therefore, advanced kidney injury and the exposure to Gd‐CA are regarded as prerequisites to develop NSF. Overall, the prognosis is poor and there is no established therapy that shows a consistent benefit. The purpose of this review is to discuss the clinical spectrum of the disease. The clinical presentation, role of co‐morbidity in disease development and manifestation, time course, prognosis, outcome, and epidemiological aspects are especially reviewed. J. Magn. Reson. Imaging 2009;30:1289–1297. © 2009 Wiley‐Liss, Inc.

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Section: Onset Of Diseasementioning

confidence: 96%

Section: Onset Of Diseasementioning

confidence: 98%

Section: Onset Of Diseasementioning

confidence: 99%

mentioning

confidence: 99%

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Nephrogenic systemic fibrosis: Clinical spectrum of disease

Mayr

Burkhalter

Bongartz

2009

Magnetic Resonance Imaging

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“…Interestingly, several studies have shown the presence of gadolinium in skin biopsies from patients who experienced NSF following injection of a GC (44)(45)(46). The technique used in these studies cannot formally discriminate between chelated and free gadolinium.…”

Section: Chemical Structure-thermodynamic Stability Relationshipmentioning

confidence: 99%

Role of thermodynamic and kinetic parameters in gadolinium chelate stability

Idée

Port

Robic

et al. 2009

Magnetic Resonance Imaging

159

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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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Nephrogenic Systemic Fibrosis

Bangsgaard¹,

Marckmann²,

Rossen³

et al. 2009

Arch Dermatol

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Background: Nephrogenic systemic fibrosis (NSF) is a serious disease that occurs in patients with severe renal disease and is believed to be caused by gadoliniumcontaining contrast agents. A detailed description of the late skin manifestations of NSF is important to help dermatologists and nephrologists recognize the disease. Observations: We studied 17 patients with NSF late in the disease. All patients showed epidermal atrophy and hairlessness of the affected regions, primarily the lower legs. Affected areas were symmetrically distributed and hyperpigmented in most cases. Eleven patients showed confluent dermal plaques with thickening and hardening. In contrast, 3 patients presented with wrinkled, redundant skin as seen in cutis laxa. Patients with NSF had significantly poorer scores than control patients on the Daily Life Quality Index (mean [SD], 11. 4 [7.4] vs 1.5 [2. 3]; PϽ.001). Conclusions: This descriptive case series of patients with NSF gives a detailed clinical picture of the skin manifestations late in the disease. It demonstrates that the clinical picture in the late stage has a varied presentation and that NSF has a significant effect on the quality of life.

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Dermal inorganic gadolinium concentrations: evidence for in vivo transmetallation and long-term persistence in nephrogenic systemic fibrosis

Cited by 190 publications

References 31 publications

Nephrogenic systemic fibrosis: Clinical spectrum of disease

Nephrogenic systemic fibrosis: Clinical spectrum of disease

Role of thermodynamic and kinetic parameters in gadolinium chelate stability

Nephrogenic Systemic Fibrosis

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