Motivation: A few months ago, I was lounging in the neurology office when someone called to ask about the possibility of brain MRI with contrast in a patient with kidney disease. The resident answered, "Of course, not!" After all, gadolinium based agents have been implicated in nephrogenic systemic fibrosis (NSF). When the resident placed the phone on the cradle, a fellow in the room smirked and remarked that our fear of NSF is overblown. He explained that cases of NSF occur rarely and that fear of litigation probably drove our prohibition. Well, just how common is nephrogenic systemic fibrosis after gadolinium contrast exposure?
For background, nephrogenic systemic fibrosis was first described in 2000 and is clinically characterized by thickening and hardening of skin with "brawny" hyperpigmentation especially of the extremities. Patients experience neuropathic pain in affected areas and suffer from flexion contractures and pressure ulcers.
Paper: Association of Gadolinium Based Magnetic Resonance Imaging Contrast Agents and Nephrogenic Systemic Fibrosis. Bhave, G. et. al. The Journal of Urology (2008) 180: 830-835. http://www.jurology.com/article/S0022-5347(08)01225-1/abstract
Results:
Number of known cases: The largest case registry for NSF (Yale NSF case registry) contains about 200 cases. Adding all other reported cases, at the end of 2006, there were at most 400-500 cases of NSF worldwide.
Relation to Kidney Disease: No case of NSF has been described for GFR greater than 30 mL/min. Cases which seemingly involved patients with GFR > 30 mL/min are likely due to calculation error since in acute kidney failure, serum creatinine levels do not instantaneously reach steady state and give rise to errors in GFR estimation.
Link with Gadolinium Exposure: More than 95% of known cases of NSF have had gadolinium exposure in the weeks to months prior to presentation. A very small minority of putative NSF cases have not had gadolinium exposure. The upper limits of lag times from gadolinium exposure to NSF are about 1-2 years.
Incidence after Gadolinium Exposure: In single center cohorts, the proportion of patients with kidney failure developing NSF after gadolinium exposure is about 2-5%. The authors challenge this assumption based on a simple calculation. Before 2000, there were no restrictions on gadolinium administration. In the ten prior years, there were 50 million MRI contrast studies, and given the 0.1% prevalence of end stage renal disesaes (ESRD) in the U.S., there have been conservatively about 50,000 MRI contrast studies performed in patients on ESRD. Given that there are at most 500 known cases of NSF, the incidence is likely no more than 1% after gadolinium exposure in patients in ESRD.
Discussion: In summary, NSF is a rare but real danger. What I thought was an especially valuable point to keep in mind is that in cases of acute kidney failure, the serum creatinine level is an imperfect measure, and the working assumption ought to be perhaps that gadolinium is contraindicated despite seemingly permissive creatinine levels. On the flip side, radiologists are hesitant to administer gadolinium in patients with GFR<60 mL/min but greater than 30 mL/min. There have been no reported cases of NSF in this group, and this cautious approach may be excessive and needs to be reevaluated.
Finally, is there any way to prevent NSF? From a pathophysiology viewpoint, gadolinium ion is toxic to human beings, and contrast agents consist of gadolinium chelated to other molecules to facilitate excretion and limit exposure of tissue to gadolinium ions. In renal failure, with prolonged exposure, gadolinium is lost from chelation and produces toxic effects. In the future, the thought is that with stronger chelating molecules, we may be able to further limit gadolinium loss from chelation and prevent toxic effects before excretion through dialysis or urination.
For background, nephrogenic systemic fibrosis was first described in 2000 and is clinically characterized by thickening and hardening of skin with "brawny" hyperpigmentation especially of the extremities. Patients experience neuropathic pain in affected areas and suffer from flexion contractures and pressure ulcers.
Paper: Association of Gadolinium Based Magnetic Resonance Imaging Contrast Agents and Nephrogenic Systemic Fibrosis. Bhave, G. et. al. The Journal of Urology (2008) 180: 830-835. http://www.jurology.com/article/S0022-5347(08)01225-1/abstract
Results:
Number of known cases: The largest case registry for NSF (Yale NSF case registry) contains about 200 cases. Adding all other reported cases, at the end of 2006, there were at most 400-500 cases of NSF worldwide.
Relation to Kidney Disease: No case of NSF has been described for GFR greater than 30 mL/min. Cases which seemingly involved patients with GFR > 30 mL/min are likely due to calculation error since in acute kidney failure, serum creatinine levels do not instantaneously reach steady state and give rise to errors in GFR estimation.
Link with Gadolinium Exposure: More than 95% of known cases of NSF have had gadolinium exposure in the weeks to months prior to presentation. A very small minority of putative NSF cases have not had gadolinium exposure. The upper limits of lag times from gadolinium exposure to NSF are about 1-2 years.
Incidence after Gadolinium Exposure: In single center cohorts, the proportion of patients with kidney failure developing NSF after gadolinium exposure is about 2-5%. The authors challenge this assumption based on a simple calculation. Before 2000, there were no restrictions on gadolinium administration. In the ten prior years, there were 50 million MRI contrast studies, and given the 0.1% prevalence of end stage renal disesaes (ESRD) in the U.S., there have been conservatively about 50,000 MRI contrast studies performed in patients on ESRD. Given that there are at most 500 known cases of NSF, the incidence is likely no more than 1% after gadolinium exposure in patients in ESRD.
Discussion: In summary, NSF is a rare but real danger. What I thought was an especially valuable point to keep in mind is that in cases of acute kidney failure, the serum creatinine level is an imperfect measure, and the working assumption ought to be perhaps that gadolinium is contraindicated despite seemingly permissive creatinine levels. On the flip side, radiologists are hesitant to administer gadolinium in patients with GFR<60 mL/min but greater than 30 mL/min. There have been no reported cases of NSF in this group, and this cautious approach may be excessive and needs to be reevaluated.
Finally, is there any way to prevent NSF? From a pathophysiology viewpoint, gadolinium ion is toxic to human beings, and contrast agents consist of gadolinium chelated to other molecules to facilitate excretion and limit exposure of tissue to gadolinium ions. In renal failure, with prolonged exposure, gadolinium is lost from chelation and produces toxic effects. In the future, the thought is that with stronger chelating molecules, we may be able to further limit gadolinium loss from chelation and prevent toxic effects before excretion through dialysis or urination.
There are a number of people who are experiencing symptoms of NSF who did not have low GFI's at time of MRI with contrast. Becuase diagnosis of NSF is not done unless there are reasons to believe patient had severe kidney problems, there may be severe underdiagnosis of gadolinium related systemic fibrosis. In fact adult onset, non-genetic mitochondriosis may be linked to blood-brain barrier compromise by weakly chelated gadolinium.
ReplyDeleteI just was diagnosed with NSF and had normal renal function
DeleteHi March 7th poster. THANK YOU for posting. I am a person who is suffering NSF type symptoms after gadolinium and have normal kidneys. I know of others in this situation. The non renal impaired victims have been overlooked and are in danger of never being recognised. If there is anything you can tell us that might help it would be greatly appreciated. Please post again. Many Thanks.
DeleteMarch 7 poster...thank you for posting. I have been suffering from NSF-like symptoms for 2 years now, but because I have normal renal function (GFR >60), it is impossible to get a gadolinium-related diagnosis. I am aware of many other patients with normal renal function who are also having similar symptoms. I hope you post again. I would like to know if your diagnosis was confirmed by a biopsy. Thank you and good luck.
DeleteHello M7,which country did you get your diagnosis in?
DeleteHi Amonymous,
DeleteCan you tell me how you finally got diagnosed? I have seen a raft of doctors who have never heard of NSF or believe one has to have kidney damage, and I have had almost all the symptoms for over two years. The rib and hip pain is intense. I feel like the insurance company is doing all it can to forestall a proper assessment and diagnosis. Any suggestions? Thank you.
Hi M7,
DeleteI was wondering if your lab results for Carbon Dioxide (bicarbonate) was in the lower range (< 23) or Arterial Blood Gas test results showed signs of acidosis (lower pH and low bicarbonate values)despite > 60 eGFR around the time you got injected with GBCA. There seems to be some research that show strong correlation between eGFR and lower carbon dioxide results where lower the eGFR appear correlated to lower carbon dioxide levels (possibly indicating acidosis). Perhaps there are people out there with normal eGFR (>60), but have acidosis going on that could trigger NSF? More I read, it seems like perhaps if NSF does occur in people with > 60 eGFR, perhaps those people may have underlying acidosis they were not aware of? Perhaps instead of screening people just for eGFR, it might be prudent to screen people for Acidosis (if Carbon Dioxide level from basic metabolic panel often ordered with eGFR is on the lower side).
My dad was recently diagnosed with NSF. His MRI was 7 years ago! We started to think it might have been NSF over 3 years ago, and it took him almost dying to get someone to do the biopsy. It was confirmed in December. His kidneys ARE healthy! His blood panels before the MRI were completely normal....which means there is something else that caused this disease in his body. He is now on oxygen all the time and has a tracheostomy tube in his throat to help him breathe because the NSF has destroyed his diaphram and is killing his lungs. I've been researching this disease for 4 years now, and the research all says the same thing, that it's kidney related.....I hate to say it, but its not. I will never have an MRI with contrast!
DeleteI'm very sorry to hear about your dad. I'm impressed that you have fought for a diagnosis and have at least won that battle. The skepticism surrounding even the idea that people with normal kidney function can get so called NSF is overpowering. Some prefer to call it GASF because the kidneys are not responsible for causing the disease. We believe that others without impaired kidneys have this disease to varying degrees, and are not being recognised. Please let what has happened to your dad be widely known. We have to prevent this from happening to others in future. We cannot be silent. Can you please say if your dad ever had any skin involvement and how they reached diagnosis. This is important to know because the lack of poor kidney function & significant skin involvement has been a significant stumbling block for people trying to get a diagnosis. Thank you for posting. Wishing your Dad & your family well.
DeleteMany people are sick with gadolinium poisoning and NSF is just one of the symptoms. The real reason that articles are not published about normal renal function is because the Pharmaceutical companies are interfering and they get manipulate the data.
DeleteRegarding possibility of NSF with normal GFR and currently used contrast, it is, of course, possible but I don't know of published reports documenting NSF with actual GFR > 30. Also, at least so far, gadolinium induced encephalopathy has resulted from intrathecal injection or repeated contrast loads in someone with renal failure. Would definitely like to see data about effects of gadolinium in people with normal GFR.
ReplyDeleteShamik, have you visited any patient blogs on gadolinium to hear the effects that gadolinium is having on previously healthy people?
DeleteNot to underestimate the patient perspective, but the internet is filled with patient blogs claiming many associations that are in the final analysis only partially true. Part of the problem is that many patients receiving MRI with gadolinium have other concurrent medical conditions that could potentially have skin findings as well. Separating one from the other is difficult.
DeleteI just want to say that I spent 15 months researching NSF and the problems associated with gadolinium before I ever joined any sort of NSF/GASF group. I did that intentionally so that I would not be influenced by other people's perceptions and misinformation. All of my research came directly from medical sources. So now here I am soon to be 24 months later and I still don't have any answers.
DeleteI agree that other medical conditions could potentially have skin findings, but what you don't understand is that there are many, many patients who have been tested for every condition and disease known to man and all of their tests have come back normal/negative. Some of them have skin changes and some don't, but the one common denominator they all seem to have is one or more (usually more) MRI with a GBCA.
What about the patients who have had gadolinium found in blood or urine, but because they have normal kidney function no one will pursue the possibility that they could be suffering from gadolinium-toxicity?
Somehow everyone needs to open their eyes and their minds to the very real possibility that gadolinium is indeed causing internal damage to everyone who ever receives it.
I am aware of many people with normal renal function (GFR >60) who are experiencing many symptoms of NSF, including skin changes. Gadolinium has also been found in blood and urine from these patients, but because they did not have severely impared renal function at the time of their MRI(s), they cannot find anyone who will even consider that they could also be suffering from gadolinium-toxicity. There was a biopsy-confirmed case of "Non'Nephrogenic" Systemic Fibrosis presented at the 2011 NSF Symposium at Yale - the patient had normal renal function. I believe there are many more cases out there, but patients with normal kidney function cannot get a proper diagnosis.
ReplyDeleteAs with most adverse drug reactions, reactions to gadolinium based contrasting agents (GBCAs) are under-reported. And as with most products that cause grave harm, doctors remain in the dark or dismiss them as not the cause. But no matter what the diagnosis may end up being for gadolinium toxicity (i.e. fibromyalgia or scleroderma) it is costing the largest employers that self-insure and the health insurers billions in added healthcare costs over the remainder of the life of the patient that has been harmed but not diagnosed. Please understand that of every bolus dose at least 1% stays in the body and the worst product, Omniscan was known by GE to break away from the chelate in the vial before it was injected.
ReplyDeletehttp://www.scribd.com/doc/76624693/ThereasonfortheexcesschelateintheOmniscan
The group of employers, (20 of the largest employers in the country) now has access not only to their claim data but the data of this consortium as well as Medicare data and will be performing reviews of the data and doctors. And you can bet this consortium is going to look at the data six ways to Sunday; it doesn’t lie like the rigged clinical trials that are all too common in scientific research these days. The healthcare delivery system is going to change rapidly and rabidly in this country so hold onto your seat and don’t be surprised if doctors that refer for un-necessary scans start getting arrested - oh that already happened didn’t it.
I don't see how the article that you referred shows that 1% of the Omniscan stays in the body or that the metal breaks away from the chelate. As far as I understood, the article attempted to use two different techniques to quantify different components in a mixture.
DeleteShamik Bhattacharyya, MD I tried to provide you with links to the articles but the posts are not going through. I hope you at least reviewed some of what I provided. In addition a recent patent application shows that they may be able to diagnose systemic fibrosis using bio-markers. The funding was interestingly from the NIH so the government has rights to the patent. I'm going to do further research but my thoughts are that GE may have matched the grant.
DeleteThere have been diagnosed cases of NSF with GFR > 30 I have seen one at GFR 69, additional risk factors were present. I have seen articles indicating that only a minor drop in GFR may be necessary if certain other factors are present. This minor drop could well apply to people with normally good kidney function.
ReplyDeleteAcute kidney injury can happen to anyone and is recognised as black box risk factor in NSF. Being transient in nature if AKI happens to someone with good kidneys it can easily be missed, but the NSF symptoms can still progress after AKI has resolved leaving a patient with symptoms that are dismissed when later their GFR reads as normal.
It has also been hypothesised a patient with normal function could develop NSF if enough culmative doses are given. This appears to be the case in one diagnosed person with no history of renal impairment.
If anyone thinks the risk is not there for patients with normal function, think again:
Even the EU medicines agency are thinking on this risk and have theorized in their 2011 safety guidelines about gadolinium,that a patient with normal kidneys could go on to deveolop NSF in the future after having gadolinium if their kidneys should later become impaired for any reason.
Because gadolinium is stored in the bones it is like a ticking time bomb waiting to go off and release into the tissues and organs...... the clock might tick a little slower in those with normal kidneys... but be sure.....it ticks.
I think that the point about transient AKI is what confounds most analyses. Using creatinine to compute estimated GFR whent the creatinine is not yet at steady state. But, sounds like there is more to the story. I would still be interested though if someone could provide a reference to an actual published pathology confirmed case of NSF in a person with adequate renal function (GFR>60). I understand that something to this effect was published at the NSF symposium at Yale, but has there been a reputable journal publication? Of course, lack of publication does not negate the possibility but makes one wonder why.
DeleteIt is my understanding that this case is being peer-reviewed prior to publication. I saw a copy of the poster presentation before it was suddenly removed, but to my knowledge it is not in the public domain. The patient had 17 MRI with a GBCA over a span of 5 years prior to presenting with symptoms. Her GFR ranged from 65 to 92 during that time period. Most of the doctors involved with this case are at University of Alabama at Birmingham so perhaps you could find out more information from one of them.
DeleteIt sounds like you might at least have an open mind about the risks associated with gadolinium. You might try re-reading some research studies and ask yourself why do so many mention finding evidence of gadolinium in the skin, liver, bones, and spleen of study animals with NORMAL renal function. And why did they find gadolinium in hip bones of patients with normal renal function as long as 8 years after their last MRI with contrast. Someone needs to be looking for evidence of gadolinium toxicity in everyone who has ever had an MRI with contrast. I suspect most of us are walking around with some degree of fibrosis going on inside of us, but until the gadolinium level in our bodies reaches that unknown threshold, most of us will not present with the "classic NSF" skin changes. I believe our damage is not readily seen with the naked eye, but it is still there. Unfortunately, the medical community is working under the assumption that the damage caused by "NSF" will be visible and then only in patients with impaired renal function.
I recently read a 2007 editorial that I think you might find interesting. It was titled, "Thorotrast toxicity: the safety of gadolinium compounds". It was written by J.F.M. Wetzels, Department of Nephrology, Radboud University Nijmegen Medical Centre, the Netherlands. I won't go into all of it here, but Dr. Wetzels pointed out that the "currently used gadolinium-based contrast agents are all chelates, which much ensure that NO free gadolinium is present in the circulation". He closed by saying, "we must keep in mind that toxic effects may occur less frequently, later, and only after repeated exposures in patients with less severe renal dysfunction".
Very sobering thoughts to say the least; so what happens to the 1% from each MRI that was left behind every time you had one? And that 1% assumes you had good kidney function and nothing else going on to allow even more to remain in your body.
Shamik, I can supply the link to the article mentioning a diagnosed person with GFR 69.6. The article itself is interesting as it discusses concurrent morbities to the development of NSF. As we know not all patients with CKD get NSF, therefore it is logical that there are other causes. This being the case it is also logical to believe that NSF is not exclusively linked to CKD. Concurrent co morbities to gadolinium such as pro-inflammatory events, acidosis, nephrotoxic drugs can affect anyone regardless of kidney function & may be all that is needed in the wrong circumstances. Wrong circumstance = being injected with a highly toxic metal. The fact is that NSF has simply not been looked for in partients with normal kidney function. I personally believe that there are degrees of NSF and at the milder end of the range could be patients with and without impaired kidney function who are presenting with myopathic symptoms either without skin symptoms or with a lesser degree of involvement than what physicians anticipate. Such cases could easily be missed/mis-diagnosed, they will never even reach the biopsy stage.
DeleteWe need help in the form of a fresh open minded approach in the research of this disease. It's a bold step, but if a group of medical students/ residents /researchers were to embark on this they would surely be at the cutting edge, where few have ventured. What do you reckon?
The link which shows GFR 69 diagnosed case of NSF is located on page 152 of the PDF version of the following document
Nephrogenic Systemic Fibrosis:
Risk Factors and Incidence Estimation
Sadowski et al Radiology: Volume 243: Number 1—April 2007 page 152
The Sadowski study actually has 2 out of 13 patients who had higher GFRs (see page 153). Patient 1 had 58.2 GFR at the time of first MRI with contrast. Patient 5 had 4 MRIs and his GFR started at 69.6, followed by 53.8, 34.6, and 49.9. As was stated previously, there are concurrent morbidities that play a part in the development of NSF; its development does not appear to be totally dependent on renal function.
DeleteI believe that NSF is truly a disease of degrees and it may not always present with visible skin changes especially in patients with normal renal function. I agree that we need a "fresh, open-minded" approach in the research of gadolinium-toxicity.
Thanks for pointing out the article. (The link to the article for everyone: http://radiology.rsna.org/content/243/1/148.long). In the text of their results, they mention that the two patients who had NSF with eGFR > 30 were in the middle of an episode of acute kidney injury when they got the MRI with contrast. In these two patients, the serum creatinine and the estimated GFR grossly overestimates the real kidney function. But, I am interested in the idea of "subclinical NSF" in other patients with mildly decreased kidney function.
DeleteShamik, I'm guessing you are presuming that the GFR and serum creatinine are over estimated due to the timing of the test or other factor? The nephrologist does note that there was only a mild to moderate drop in function. Whether the renal functiion in real terms dropped much further or not, at some point the GFR was a reasonably healthy 69.6 in one patient. If the 69.6 GFR was estimated in the middle of an AKI episode, I'm wondering how much higher the GFR might have been prior to the episode. I guess we will never know.
Delete"Subclinical NSF"... I think this is a very real possibility and may account for the long delay some patients experience before displaying the skin symptoms. Subclinal NSF is suggested in this article about a liver transplant patient in whom gadolinium deposits were found 3 years after gadolinium with no skin involvement. http://www.eblue.org/article/S0190-9622(09)00494-0/abstract
Gadolinium has been found in the tissues of people with normal function so maybe it is also a subclinal form just waiting for something to trigger the fibrotic process.
This may interest you Shamik; this article deviates from the typical textbook presented picture of NSF and describes subclinical and atypical symptoms. It suggests that NSF could easily be missed in some patients. We believe it is being missed in the non-renally impaired sector of the patient population especially where symptoms are not visually dramatic.
Deletehttp://www.scribd.com/doc/55205280/Nephrogenic-Systemic-1
"Of course, lack of publication does not negate the possibility but makes one wonder why."
ReplyDeleteBecause they are all in denial that a problem exists. But, math does not lie. Presuming that 1% of GBCA's remain after injection, that means that after 10 contrasted MRI's there's 10 PERCENT of GBCA remaining in a person.
Sorry, if a person with good kidney function is still excreting high levels of gadolinium, months or years after exposure, when it is supposed to clear within 24 hours, there is a definite problem.
The idea that gadolinium persists in the circulation after months and years post contrast has been brought up multiple times. I would be interested if someone could find an article with measurements showing the persistence of gadolinium excretion for a long time after contrast administration. The part that is a bit confusing is why should "1%" of contrast be retained in the ciruculation when it is being processed by the kidney multiple times a day? Of course, the other possibility is that the contrast is trapped in other tissues and slowly released with time. Has this issue been studied?
DeleteI would share my labs with you if you agree to keep them confidential and provide me with an email address. Mine is shha2002 at yahoo.com. I am not aware of having AKI and have always had normal functioning kidneys but I have high levels of gadolinium in my urine and gadolinium has been found in my tissue. The labs are common now. After I connected the dots I called every honest lab in the country and now gadolinium is a metal they test for on most of their panels.
DeleteIf you haven't read Swaminathan's patent you might find it useful to do so if you are interested in other reasons for the retention of gadolinium. My understanding is that some of the chelates used in a few of the products have a preference for iron and zinc....so if someone has excess iron or zinc and gets injected with one of these products, the chelate leaves the gadolinium in its free state in the body and binds to the iron and zinc.
http://www.scribd.com/doc/80440553/Patent-Application-Publication-Swaminathan
Thanks! I may contact you confidentially in the next month.
DeleteCheck out this article, indicating that it is well known that gadolinium is stored in the bones in patients with healthy kidneys, and that there is now evidence that it is retained in the brain: http://www.ajnr.org/content/early/2015/12/10/ajnr.A4615.full.pdf+html
DeleteI have circulating blood levels of gadolinium currently since last MRI in Sep and Dec 2010.
ReplyDeleteI also have + skin biopsies.
Also,why do you refer to the NSF cases in the pathmax.org only which Cowper w co horts only say they have 345 registered NSF cases, then you say 2006 there are about 400-500 cases. When in fact, if you listened to the 2010 NYAS.org that Cowper and pals presented, along w Jack Gauldie who says this is the tip of the iceberg and to expect tens of thousands of cases in the next decade. Additionally, Panel 1's comments say, "radiologists are terrorists". Get your information current. We have copies of the autopsies and NSF cases and multi district lawsuits and know which attorneys are complicit.
ReplyDeleteThe article re to The reason for excess chelates in Omniscan is orginally found in Journal of MOLECULAR STRUCTURE, pg 348, 1995, Too old information.
ReplyDeleteI don't believe the article by Dr. Wetzels in the Netherlands states contrasts are all chelates? Really, then why do my MRI reports strictly state "Gadolinium", not even the brand name is listed, so I have no idea, yet which company made it, but I will find out. Chelates are radionuclides, DTPA etal. deceptive trade practice act. sound familiar? How can you measure the tesla 1.0-3 and signal and magnetic images?
Thanks everyone for participating in this discussion. Took me some time to review all the evidence that has been pointed out. I think that there is good data to suggest that there is residual deposition of gadolinium (likely less than 1%) into the tissue of even individuals with healthy kidneys exposed to gadolinium based agents. Then, of course, the next question is what is the clinical significance of the residual gadolinium? I think that this is where we are in uncharted territory. As some of you point out, this exposure is dangerous and could give yet unrecognized disease syndromes. On the other hand, human beings are exposed to many heavy metals that are harmful in high concentrations but apparently tolerated OK in low concentrations. In the next couple of weeks, will try to find out if anything more is known in this topic and possible "subclinical NSF."
ReplyDeleteAlso wanted to address two other themes that have come up repeatedly. 1) I try to stay away from data from patent applications. These applications are by design meant to be biased in favor of some idea/design and are NOT peer reviewed. There is obvious conflict of interest in these articles. 2) Doctors are often stuck in the difficult position of balancing risks/benefits of diagnostic and therapeutic procedures. For example, some items as common as "blood-thinning" with coumadin/warfarin carries about a 2% annual risk of life-threatening bleeds. Yet, we have to prescribe warfarin because the risk of not using outweighs the benefits. Similarly, with imaging procedures such as CT scans and associated radiation, the choices are not free of consequence such as possible radiation induced cancer. At least from my own personal experience, doctors struggle with these decisions and do not take them lightly. I don't know if gadolinium based contrast agents are going to go away, but we can at least illustrate more clearly the risks! Again, thanks everyone for participating.
I'm not sure that the true risks associated with GBCAs will ever be clearly known unless everyone exposed to GBCAs is screened for gadolinium-toxicity. As it stands now, the only patients who are evaluated in any way are those with impaired renal function who present with the skin changes and/or joint contractures currently associated with NSF.
DeleteI understand that there are inherent risks with other drugs and procedures, but for the most part those risks are known and clearly conveyed to the patient. And in some cases simply stopping the drug or administering another drug or treatment can resolve the issues.
In the case of gadolinium-based contrast agents, patients do not fully understand the risks involved and they do not know that they could fall victim to an incurable, potentially lethal disease process. I have no doubt that doctors do not make decisions about the use of GBCAs lightly, but in order to make a truly informed decision about the safety of GBCAs, wouldn't you need to know that studies had been done on the long-term effects in a diverse patient population? And I'm not just talking about looking for the "visible" signs of NSF especially in the non-renally impaired. The damage caused by gadolinium goes far beyond what can be seen by the naked eye.
Thanks for listening Shamik; an open mind on this is a good start..... hang about
DeleteShamik, have you read the 2007 article by J.L. Abraham, et al entitled. "Dermal inorganic gadolinium concentrations: evidence for in vivo transmetallation and long-term persistence in nephrogenic systemic fibrosis"? If not, you should. Among other things it states, "The recognition that rare earth metals are deposited in bone and other sites, with slow long-term clearance, provides strong support for the hypothesis that Gd deposition in bone after Gd-enhanced MR imaging scans may be a long-term internal source of Gd."
DeleteHe goes on to say, "Although NSF has thus far been seen only in patients with severe renal disease, it remains unknown whether persons exposed to GBMCA (regardless of renal function at present) may later develop renal failure or other bone demineralizing conditions, which might lead to Gd toxicity from comobilization of Gd from bone stores."
So, possible gadolinium toxicity - not NSF- in the non-renally impaired patient...Hmmm
There is good evidence to suggest that gadolinium is toxic to all people, with the potential to trigger the process of fibrosis. People with good kidneys are not immune to other forms of fibrosis so why would they be immune to fibrosis from retained gadolinium. The "N" of NSF is beginning to annoy me and several reputed experts have called for a name change, because using the "G" word is appropriate.
DeletePerhaps with a name change there would be a less closed attitude about the disease and a realization that what is being experienced is the same disease just different degrees, as opposed to being regarded as gadolinium toxicity/reactions for the non renal impaired yet more specifically identified as what is called NSF for those with impaired kidneys.
Doubtless the manufacturers will contest any suggested name change that could identify a far broader range of victims of the disease whilst putting the blame squarely on their own product.
I also think this disease should be renamed "GASF" and I believe there is mounting evidence to support that. However, I think the chance of that happening is very slim especially now that the new proposed "scoring and diagnostic criteria" does not require any history of gadolinium exposure.
DeleteNo gadolinium exposure LOL!
DeleteWhen the Gd3+ dissociates from the chelate, what happens to the radioactive chelate? is is measurable in the blood, or does it linger also as a separate measurement.
ReplyDeleteThe patent articles are submitted by Cowper SE, and his co horts..My MD had the nerve to tell me to "take as much zinc as I wanted", which I never did, since she did not have baseline levels that I ever saw, maybe in some hidden discovery chart, even so, I can get retested for zc and Fe+.
Large amounts of zinc have been found in urine after gadolinium administration; This is consistent with the transmetallation theory, which indicates that the chelate has a preference for excess zinc and breaks from the gadolinium in preference for zinc and binds to it. The chelate is designed to leave the body so takes the zinc and other minerals with it. Hence why high levels show up at in the urine afterwards.
DeleteNot sure what might happen to any left over chelate if it didn't just eventually leave the body. Anyone know?
I'm not sure what happens to the excess chelate, but I did find a good article on the science of all this. The 2009 article by Sherry et al is entitled "A Primer on Gadolinium Chemistry". The doi: 10.1002/jmri.21966
DeleteShamik, I was wondering if you ever found any information about the first biopsy-confirmed case of "Non-Nephrogenic Sytemic Fibrosis" in a patient with normal renal function that was presented last May at Yale. It will soon be one year since it was presented and I have yet to see any mention of it except by some of those who were in attendance at the symposium. I assume the peer-review process prior to publication can take a while, but since the lives of others might be at risk I would hope that process could be expedited.
ReplyDeleteI was contacted off line about this blog so sorry for the late entry.
ReplyDeleteBecause I did not fit into the renal failure category was misdiagnosed in 2006. After two years and second look because of life long renal disease (no dialysis and consistent GFR >30) I was diagnosed with NSF by punch biopsy. Since then I have had other tests that show fibrotic changes. There are many more factors that went into my risk of NSF so I am sure there are others like me. My case is in NEJM, I have attended several NSF Yale conference and have met in person and virtually more that a few pts with NSF. Although GASF may have changed its name again and may be on a down slope, the risk is still real as are the patients. I am not saying no contrast as I may have needed some contrast for the DVT that started this all but there is an obligation to disclose the risk, advocate for less use, lower doses and truly allow for informed consent to the patient.
Thanks for starting this conversation and please know that even if people think there are no new cases and sadly there are perhaps fewer of use left to teach, at least realize those of us that have it (diagnosed of not) still need the hope of a treatment. Thanks again
I've had Brain MRI with Magnevist done about 3 weeks ago. Blood test I got about 2 weeks before MRI showed that I had eGFR in the normal range. I also got more blood work done few days after the MRI and those also showed normal eGFR numbers. However, ever since the MRI, I've been having very disturbing deep bone pains in my thigh and hips along with skin tightness and burning sensations. I did get few bouts of minor bumps showing on my legs and arms, but they seemed to go away on their own after few hours. Some of the other symptoms include unusual tenderness in my left calf and sudden bouts of shortness of breath, but I am asthmatic, so the breathing problems could be due to my asthma going out of control. I do not have any visible skin symptoms. I keep trying to tell myself it's impossible for me to get NSF with normal functioning kidneys, but symptoms are real and they are really freaking me out. Any advice will be greatly appreciated.
ReplyDeleteI understand your concerns and I think they are very legitimate. My advice to you is to learn all that you can about gadolinium and gadolinium-based contrast agents. And don't just focus your research on NSF or you won't discover all the facts.
DeleteI've been dealing with as yet unexplained health issues since early 2010 after my 5th MRI with Magnevist which coincidentally was of my brain too. Unfortunately, it appears that the medical community is still working under the belief that the risks associated with gadolinium-based contrast agents are only a concern for the severely renally impaired. Based on the published research that I've read, that does not seem to be the case. My personal opinion is that bad kidneys simply allow even more gadolinium to remain in the body at one time, which in turn results in more gadolinium reaching the skin and underlying tissue. When that happens, you "see" the skin changes that are associated with NSF. But everyone needs to remember that the skin changes are just one part of the disease process; it's the damage being done on the inside that seems to be totally overlooked.
For you or anyone else who is having unexplained health issues that you feel might be related to the contrast you received for an MRI or MRA, there is a fairly new Yahoo support group called "MRI-Gadolinium-Toxicity" that you might want to check out. The group is focused on learning all the facts related to this problem and they hope to bring about change based on published medical research and not just on their personal opinions; they have a fairly extensive group of files and links to published, peer-reviewed research on this. If you read the articles, you'll soon realize that the potential for harm does exist for everyone, but probably to varying degress depending on how much gadolinium remained in your body where it seems most of it will ultimately deposit in your bones. That's why it never gets removed by the kidneys - gadolinium chloride - the free gadolinium - is considered to be a "bone seeker". This might explain why gadolinium has been detected in hip bones removed from patients with "normal" renal function as long as 8 years after their last exposure to a gadolinium-based contrast agent.
And multiple articles talk about the "cumulative dose risk" for everyone at some unknown point in the future, including those with normal renal function. Even if less than the etimated 1% of each standard dose remains in a patient's body, what happens when you have multiple MRIs or higher than the standard dose? How much can the human body tolerate? Does anyone know???
I had 2 MRI's 8 days apart with contrast in March 2012. I have normal renal function. About 4 weeks later I developed paresthesias (tingling, burning, stinging) in my lower legs and feet; bilateral and symmetrical. I have no skin changes. These symptoms have persisted. 4 months after contrast exposure a 24 hour urine excretion was 2.6 microgram/day and a repeat 1 month later was 2.1. The paresthesias persist. Is there a way to hasten the exit of gadolinium from the body; is CaNa EDTA being used; I have seen one report.
DeleteI hope somebody is still on this thread. I had an MRA 7 months ago.
ReplyDeleteI am glad someone actually had their gadolinium measured. Why is this not done more often?
Gadolinium has made me sick in the past, in fact, I went into renal failure AFTER gadolinium in 2010. This time, after a scan in July 2012, it is much worse....same symptoms as others are describing
I have had 24 hour urine collected several times and it has remained extremely high. A few weeks ago (7 months after the scan) it had not dropped from when it was measured one months after the scan (approx 2.4).
I actually paid a CLIA lab out of pocket to do the first one because none of my treating physicians would do it even when i was hospitalized. The most recent time is was ordered by a heavy metal toxicoligist at a University Hospital.
Why is this not done more often? Also, since there are quite a few of us with elevated levels, why does nobody seem to care about it? Free gad is known to be toxic. Nobody disputes that...so why are we not getting recognized the way renal failure patients are? Physicians should not have a problem with understaning why we are sick....it seems like it is being avoided by docs, payors and FDA
BTW - chelation can be dangerous in and of itself. Do not jump into it.
Does anyone have a doc who has actually acknowledged that your problem is from gad? If you do I would fly anywher in the country to see them
Despite that my usual renal function is good I also had rapid onset symptoms of acute kidney injury which would have caused me to retain gadolinium. I have not been able to get my urine tested but have evidence of fibrosis seen in affected & biopsied tissue.
ReplyDeleteMy doctors do acknowledge that I have reactions [long term] to gadolinium but they want to think that NSF is confined to those with chronic renal disease. If the fibrosis I have is not enough of a wake up call, I don't think they will accept the presence of gadolinium in urine samples as evidence of toxicity in people. It all a case of what they can bring themselves to believe.
We the patients sadly know the truth.
Wow, what an informative thread. I have a background in Earth Science & it is insane to me that a toxic metal would be injected into a human body. Brings back memories of how popular mercury fillings were a while back.
ReplyDeleteGd is a RARE earth element. It is completely foriegn to our bodies. And yes, it WOULD bind with calcium, due to ionic size & charge.
Administering high concentrations of Gd is totally irresponsible, considering the risks are not being properly considered.
Thanks for the articles - I am booked in for an MRI w/contrast & am now informed enough to refuse Gd. I will print the scientific papers & hand them to the "Dr".
My thoughts are with all the sufferers -
Why are all the threads posted by anonymous??
ReplyDeleteIt is a very common name, many of us have it. My sympathies if you are also affected by gadolinium. It helps to share experiences, please do.
Deletedoes anyone have any updates? My son had his second MRI 4 weeks ago and has been to a toxicologist and 24 hr urine on day 9 showed loads of Gado. He has pain in hips, legs joints, and muscles. Using clay baths but is desperate for some real chelation therapy. Does anyone have a reputable doc to give it?
ReplyDeleteGlad to see this article and the various posts. I only had an MRI with gad done this week. I was told it was safe even though I said I wanted to know the risks. I'm not even convinced I needed the MRI and think it will show nothing. Anyway, the first night I got quite bad backache low on one side - I have had this before when on certain antibiotics and my GP changed one of them for that reason, The backache wore off, but on day 2 after MRI I got sudden onset hand pain on the side I had had the injection. It was somewhat alleviated by elevating my arm but now I have quite bad wrist pain (same side) going up into my upper arm area and I have weakness in that hand and arm - could not use a knife to cut an onion this evening, Also I have a burning sensation in hand and arm. I am sure this is related to the MRI injection. I am planning to see my GP but I already know he will suggest I sprained it or something since I had no immediate reaction in radiology department and I already feel I will not be believed. I think I have normal kidney function.
ReplyDeleteI am concerned by my wrist/ arm symptoms and I want to say if there is anyone out there who would like to follow my case of post gad anything, then I'd be happy for them to do so. My symptoms may go away (I am hoping) but can't understand why I'm having any reaction days later when it says everywhere I have read that gad is meant to clear your body in 24 hours. If it's still in my system then from what I am reading I must be being poisoned. Is there any other explanation?
I feel slightly pin needles sensations, they were more intense after the MRI but 2 days on they are disappearing. Should I be concerned? I have perfectly normal kidney function and they used the safest agent, Gadovist.
ReplyDeleteA recent study by Errante et al showed a progressive increase in the unenhanced T1 signal intensity in the dentate nucleus (part of the brain) of patients with normal kidney function who had multiple contrast-enhanced MRIs. All the patients had MS or brain metastases. Interestingly, all the Gadolinium-based Contrast Agent product lableing say that it will be deposited in brain tumors and brain lesions. What isn't known is what long-term effects that might have.
ReplyDeleteI don't know if this site allows sharing info about other sites, but there is a new website dedicated to providing factual information about Gadolinium retention in patients who do not have severe kidney disease. The URL is www.GadoliniumToxicity.com
I had an MRA in 2012 and had a reaction to it. I went back to the hospital the next day and they said it was cellulitis and nothing to worry about. I had to take 2-different antibiotics to get rid of it. After that I started having all kinds of problems. I am convinced I have NSF but the Drs just act like I'm crazy. One even said " you don't want this disease". What was he implying. I certainly don't want it, but if I can't get a diagnosis then how can I get help to stop the progression. I watch my skin change, my joints hurt and the hip/rib pain is quite bad. Please help me find a Dr who might listen to me without some pre conceived notion that a want this horrible disease. ( what for sympathy or money). I have children and a bright future. I want to be functioning in their lives for s long time to come. Thank you anyone
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ReplyDelete