Gadolinium is quantifiable within the tissue of patients with nephrogenic systemic fibrosis

High, Whitney A.; Ayers, Reed; Cowper, Shawn E.

doi:10.1016/j.jaad.2007.01.022

Cited by 144 publications

(104 citation statements)

References 7 publications

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“…A contamination of our samples by an iron-containing microtome blade could be excluded using a diamond knife and avoiding any contact of our samples with iron-containing surfaces. The quantitative data of other authors (18,(31)(32)(33)(34) revealed intralesional Gd amounts in the 5-to 106-ppm range. Actually, these deposits still persisted 3 yrs after the last Gd administration.…”

Section: Discussionmentioning

confidence: 80%

“…First reports of Gd deposits within skin specimens of patients with confirmed NSF were published in 2007 (18,(31)(32)(33)(34), supporting a causal relationship between Gd exposition and NSF; however, there may be triggers of the disorder other than Gd indicating that pathogenesis of NSF requires a pattern of premises that facilitate and promote fibrosis (53).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, the presence of Gd in cutaneous biopsies of patients with NSF was demonstrated by two groups that applied scanning electron microscopy/energy-dispersive x-ray (18,(31)(32)(33) and inductively coupled plasma mass spectroscopy (34). The element visualization in tissue paraffin sections was done by backscattered electrons.…”

mentioning

confidence: 99%

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Ultrastructural Evidence of Dermal Gadolinium Deposits in a Patient with Nephrogenic Systemic Fibrosis and End-Stage Renal Disease

Schroeder¹,

Weingart²,

Coras³

et al. 2008

Clinical Journal of the American Society of Nephrology

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Background and objectives: The pathogenesis of acquired nephrogenic systemic fibrosis recently described for patients with renal insufficiency and a history of exposition to gadolinium-based magnetic resonance contrast agents is not completely understood. A role for circulating fibroblasts in the fibrosing tissue is hypothetical, and the mechanism of the assumed trigger function of gadolinium remains elusive.Design, setting, participants, & measurements: A skin lesion on a 76-yr-old man with symptoms of nephrogenic systemic fibrosis lasting 5 mo was studied at the ultrastructural level. After confirmation of he diagnosis by histopathologic methods, the presence and distribution of gadolinium, iron, calcium, and magnesium by energy filtering transmission electron microscopy was also examined.Results: The performed electron spectroscopic imaging and electron energy loss spectroscopic analyses on deparaffinized samples revealed deposition of gadolinium in irregular small aggregates that adhered to cell profiles and collagen fibers of the connective tissue, forming a perivascular "gadolinium-deposit zone" in the skin. Traces of iron signal were demonstrated in singular gadolinium-positive deposits, and iron presence was found in adjacent connective tissue. The ultrastructural cell analysis of the lesion showed among numerous poorly differentiated fibrocytes also higher differentiated cells with myofibroblastic characteristics, including bundles of intermediate filaments and attachment plaques in the cell periphery, indicating an ability of lesional fibroblasts to differentiate into myofibroblastic cells.Conclusions: These findings support the pivotal role of gadolinium chelates in the development of nephrogenic systemic fibrosis.

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Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

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Ultrastructural Evidence of Dermal Gadolinium Deposits in a Patient with Nephrogenic Systemic Fibrosis and End-Stage Renal Disease

Schroeder¹,

Weingart²,

Coras³

et al. 2008

Clinical Journal of the American Society of Nephrology

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“…We have noted (15) [32][33][34]. Chemical analysis would suggest that, once deposited, gadolinium may collect and be retained indefinitely within the tissues, including skin and bone (35). This leads to the suggestion that risk may be altered by the selection of contrast agent and by controlling the cumulative dose exposure.…”

Section: Nephrogenic Systemic Fibrosis (Nsf)mentioning

confidence: 99%

“…Within the following months several other centers reported gadodiamide exposure in patients with NSF (14-19) and a single case after exposure to gadopentetate dimeglumine. In addition, High et al (20,21) detected free gadolinium in tissues affected by NSF. Patients who developed NSF after GBCA exposure have mostly been shown to have stage 5 chronic kidney disease (glomerular filtration rate less than 15 mL/min).…”

Section: Nephrogenic Systemic Fibrosis (Nsf)mentioning

confidence: 99%

Nephrogenic systemic fibrosis versus contrast‐induced nephropathy: Risks and benefits of contrast‐enhanced MR and CT in renally impaired patients

Martín

Semelka

Chapman

et al. 2009

Magnetic Resonance Imaging

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Magnetic resonance imaging (MRI) and computed tomography (CT) have become essential to diagnostic evaluation of many, or most, important medically and surgically treated diseases. It is important to consider comprehensively the implications in making decisions when choosing one or the other cross-sectional imaging modality. Factors to consider include the relative risks of the contrast agent. Other factors include the relative procedural risks, including radiation risks and the relative expected diagnostic yield of the examination technique (1,2). In this review we describe both nephrogenic systemic fibrosis and contrast-induced nephropathy to compare the implications with regard to relative risks and benefits of contrast-enhanced MRI or CT in patients with impaired renal function.

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Imatinib mesylate treatment of nephrogenic systemic fibrosis

Kay¹,

High²

2008

Arthritis & Rheumatism

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141

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Objective. To examine the effectiveness of imatinib mesylate in the treatment of nephrogenic systemic fibrosis (NSF).Methods. Two patients with stage 5 chronic kidney disease and NSF were treated with oral imatinib mesylate at a dosage of 400 mg/day. Skin thickening and tethering were assessed using the modified Rodnan skin thickness score (MRSS), and knee joint flexion contractures were measured with a goniometer.Results. Each patient displayed progressive reduction of skin thickening and tethering, with a steady decrease in the MRSS, following the initiation of imatinib mesylate treatment. The patient who had knee joint contractures achieved increased knee extension with passive range-of-motion exercises once his skin thickening and tethering had begun to decrease. Within weeks of stopping imatinib mesylate, the skin changes recurred in each patient. Recurrent skin thickening and tethering again improved in the patient who resumed taking imatinib mesylate for longer than 2 weeks. Skin biopsies performed both before and after initial dosing of that patient revealed less fibrosis and less staining for type I procollagen after imatinib mesylate treatment, but essentially unchanged tissue gadolinium content.Conclusion. Imatinib mesylate treatment decreases fibrosis and results in the relatively rapid and steady improvement of skin changes and knee joint contractures in patients with stage 5 chronic kidney disease and NSF, despite the persistence of gadolinium in the tissues. Because skin changes recurred after discontinuation of imatinib mesylate, the duration for which treatment may be required is undetermined.

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Gadolinium is quantifiable within the tissue of patients with nephrogenic systemic fibrosis

Cited by 144 publications

References 7 publications

Ultrastructural Evidence of Dermal Gadolinium Deposits in a Patient with Nephrogenic Systemic Fibrosis and End-Stage Renal Disease

Ultrastructural Evidence of Dermal Gadolinium Deposits in a Patient with Nephrogenic Systemic Fibrosis and End-Stage Renal Disease

Nephrogenic systemic fibrosis versus contrast‐induced nephropathy: Risks and benefits of contrast‐enhanced MR and CT in renally impaired patients

Imatinib mesylate treatment of nephrogenic systemic fibrosis

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