Oxalate: Is it responsible for Gd toxicity/ GDD or is it an incidental finding?

The Wagner research team at UNM have proposed a novel theory. That oxalic acid breaks apart bonds in all GBCAs, not only Omniscan (the weakest bonds) but all the way through to Dotarem (the strongest bonds). But does this occur in humans?

To set the stage.. In humans the following are the current theories:

1. the vast majority of oxalate (oxalate is the salt of oxalic acid.. so essentially the same thing, they are not different) is present in the kidneys. Only trace amounts of oxalate is evident in organ systems. So, the probability of GBCA breakdown by oxalate in other organs than kidneys is extremely unlikely, because there is extremely minimal amounts everywhere else other than kidneys.. So the theory would have to be based on all of the breakdown is occuring in the kidneys, and the detached Gd travels to all the other organs.

2. The majority of renal stones are formed of Ca-oxalate (70-80%), so this is why so much of the oxalate is located just in kidneys.

3. Renal stone formation is based on the following theory: Randall;s plaques form in the interstitial tissue in the renal papillae, the terminal portions of the renal pyramids where the collecting ducts open into the minor calyces (the beginning of the actual renal collecting system). Randall's plaques are made up of Ca-phosphate. These Ca-phosphate kernels then serve as the framework that renal stones, especially Ca-oxalate renal stones, form around. These stones as they enlarge eventually protrude into the calyces and thereby form renal stones in the collecting system.

4. The UNM theory appears to be based on their work on rodent kidneys. It may be unreasonable to extrapolate renal findings to the remainder of the animal, even if the animal is a rodent, and not the additional extrapolation into humans. This because the vast majority of oxalate is located in the kidneys.

5. Ca- // Carbonate // Phosphate. All three of these molecules are well known to interact with Gd-. I am not certain if the observation is not simply the observation of known interactions with the complex ionic exchange that Gd undergoes.

6. As I have written in earlier blogs, novel theories like this, the prominence of oxalate in Gd toxicity, may well be correct. Because it is so unique, to be considered plausible it must be shown by at least 2 other independent groups. The groups with the most experience with animal research with GBCAs are the research groups of Bayer (headed by Dr Pietsch) and by Guerbet. If they come to similar conclusions, then I would accept that this theory would be a close approximation to truth.:that oxalate is a principle molecule responsible for Gd toxicity (GDD).

7. Then what are the nanoparticles? If they contain Gd then this should be readily shown with ICP-MS or ICP-OES (inductively coupled plasma optical emission spectrometry). Otherwise my opinion is these could be any number of tiny blobs, including clumped proteins, such as mal-formed non-folded proteins.

There is no value to debating this subject at this point. I think it highky unlikely that oxalate plays a prominent role in GDD formation. I am prepared to have more confidence, in fact a great deal of confidence in this theory, if these findings are independently observed by two other groups, which could be by Guerbet or Bayer, or university based such as the lab by Mike Tweedle at Ohio State..

In the meantime don't stop eating nuts or drinking orange juice, because you want to lower your intake of oxalate.,. Presently the overwhelming data in the nutritional literature is that they are healthy.

Richard Semelka, MD