Gadolinium Toxicity

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NSF Diagnosis made by means of Elemental Bioimaging and Speciation Analysis

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A novel approach to diagnosing Nephrogenic Systemic Fibrosis, better known as NSF, was recently published by Birka et al in Analytical Chemistry. Birka and his colleagues used the combination of inductively coupled plasma mass spectrometry (ICP-MS), laser ablation (LA) ICP-MS for elemental bioimaging, and hydrophilic interaction liquid chromatography (HILIC) ICP-MS for speciation analysis, which allowed them to diagnose a case of NSF.  While the article, Diagnosis of Nephrogenic Systemic Fibrosis by means of Elemental Bioimaging and Speciation Analysis, is very scientific in its details, there are facts to be learned by patients as well.

Skin biopsy specimens of NSF patients that were investigated by various techniques, found the presence of gadolinium deposits were mainly in the deeper regions of the subcutis (fat and connective tissue).  A correlation of gadolinium with calcium, sodium, and phosphorous was observed in all cases.

The case report in this study involved a young woman who exhibited characteristic symptoms of NSF that began in 2011.  Her clinical history included renal failure and kidney transplants from living donors in 2004 and 2006; the authors noted that she still has dialysis-dependent kidney insufficiency.  The patient had an MRI in 2002 with Magnevist (Gd-DTPA) and in 2005 with ProHance (Gd-HP-DO3A).

In 2013, a skin biopsy was taken from an affected area.  Biopsy samples were investigated by means of ICP-MS, LA-ICP-MS, and HILIC-ICP-MS.  The authors noted that this combination of analytical techniques provided complementary information on the total gadolinium concentration, the distribution of gadolinium within skin sections of a NSF patient, as well as the detection of further gadolinium species.  Distribution maps of gadolinium, phosphorous, and calcium were generated.  The results suggest the presence of insoluble deposits of GdPO4 in the tissue section.  A correlation between gadolinium and calcium was also found.  While more investigation is needed, the proven correlation between these three elements led the authors to conclude that gadolinium is accumulated and stored as insoluble deposits for a long period of time.

The methods of analysis in this study allowed for the macrocyclic GBCA Gd-HP-DO3A (ProHance) to be identified and quantified in the patient’s skin biopsy.  The “intact” GBCA was found in the skin biopsy that was taken 8 years after the patient’s MRI with ProHance.

This study provided more detailed insight into the development of NSF based on elemental and molecular information, and a case of NSF was diagnosed by mass spectrometry for the first time.

Birka, M., Wentker, K. S., Lusmöller, E., Arheilger, B., Wehe, C. A., Sperling, M., … Karst, U. (2015). Diagnosis of Nephrogenic Systemic Fibrosis by means of Elemental Bioimaging and Speciation Analysis. Analytical Chemistry, 87(6), 3321–3328. http://doi.org/10.1021/ac504488k

Sharon Williams


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