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On May 27, 2015, JAMA Dermatology published a Case Report by Larson et al that described a biopsy-confirmed case of “Nephrogenic Systemic Fibrosis Manifesting a Decade after Exposure to Gadolinium”. According to the report, a long-term hemodialysis patient was exposed to a gadolinium-based contrast agent several times between 1998 and 2004 during magnetic resonance angiography (MRA) of his abdominal vessels and arteriovenous fistula. Ten years later, in 2014, he developed new dermal papules and plaques. The diagnosis of NSF was made based on the findings of a biopsy of affected skin which showed thickening of collagen, CD34+ spindle cells, and increased mucin in the dermis. (Information about the agent(s) and dosages are not provided).
Prior to this case, the authors noted that the longest documented time after exposure to gadolinium to NSF manifestation was 3 ½ years.
This case shows that even in patients with severe renal disease retained gadolinium can take many years before causing “visible” evidence of a problem. The authors concluded that, “Although the use of gadolinium contrast agents in patients with kidney failure has markedly decreased, patients with exposure to gadolinium years to decades previously may manifest the disease”. (more…)
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). (more…)
Why does a Gadolinium Toxicity diagnosis have to be full-blown NSF (Nephrogenic Systemic Fibrosis) or nothing at all? Patients with normal kidney function have been trying to get an answer to that question for years now, but for some reason no one is listening.
NSF, which can occur when someone with severe kidney disease retains large amounts of Gadolinium, is probably the worst manifestation of Gadolinium Toxicity. But what happens to people who retain less Gadolinium? Couldn’t those people also be adversely affected, but perhaps to a lesser degree than full-blown NSF?
We believe Gadolinium Toxicity is a “disease of degrees” which can manifest itself in many ways depending on how much Gadolinium someone retains. Since free Gadolinium is toxic, it would seem that the severity of each person’s symptoms will likely depend on the total amount of Gadolinium retained from the administered Gadolinium-based Contrast Agent. (more…)
So why am I talking about an iceberg on the Gadolinium Toxicity website? Let me explain.
Not long after I started researching NSF and Gadolinium in early 2010, I saw a reference to an editorial by Dr. Henrik Thomsen of Denmark that had been published in 2008. The title was, Is NSF Only the Tip of the “Gadolinium Toxicity” Iceberg? The title caught my attention and really made me think. It took me a while, but I finally managed to find the editorial. After reading it, I had more questions than answers.
It seems that in the early 1990s, there was already concern about the stability of the nonionic linear GBCAs, and the macrocyclic agents were found to be significantly more stable in serum. It was known that transmetallation with other metal ions in the body was more apt to occur with the DTPA-based chelates, and when transmetallation occurs it results in the toxic Gadolinium ion remaining in the body. Dr. Thomsen asked, “Why were nonionic linear chelates chosen instead of macrocyclic chelate?” That is a very good question.
For those of us in the U.S., a better question might be, why did it take the FDA longer to react than the European Medicines Agency (EMEA) and the Japanese authorities? (more…)