Metal levels in urine pre- and post-provocation/chelation. Understanding what they mean.

Native urine (unprovoked) levels simply reflect how much metal is coming out of urine on its own. There is a relationship to how much metal is present in the body, and this relationship is strongest with metals that are transient in nature (Bismuth for example). For metals that have greater persistence (general reflected retention / deposition) this value is less reliable. Therefore the requirement of using a provoking agent/ chelator.

The level of elevation of a metal post-chelation is most often a reflection of how effective the chelator is at removing the metal (best represented by the log stability constant), and not so much how much of the metal is in your body (and may be causing toxicity).

For example if Gd is not much elevated following provocation/chelation with DMSA or DMPS, this does not mean there is little Gd present in you, it mainly reflects that these are poor chelators for Gd.

Chelation and provocation are always most accurate when using the best available chelator (that is highest log stability constant) and that it is in a form/delivery route that can enter the circulation.

So I would always use iv DTPA (at the present time) to evaluate for Gd or lead because of the high stability constant with these metals.

Other chelators may be better for other metals, such as DMSA is quite often better for mercury.

The future for chelation is to develop chelators with high stability constant for various specific metals. For example I am not sure what is best for chromium or platinum as examples. Thois is a science that needs to develop more.

Also readers will know that I always use 24 hour urine measurements. This for the simple explanation that I want as accurate a representation of the metal quantity leaving the body as can reasonably be obtained. It is generally recognized that there is diurnal variation in various elements in the body, and their elimination, so to control for the uncertainty of what the diurnal variation is, I simply obtain data for the full 24 hours.

Standardization is always critical for all test. Post chelation I always start collecting the 24 hour sample soon after the chelation (after the first urination) which may have occurred during the chelation. Thats is because urine in the bladder at the time of chelation start would not have experienced the chelator.

I generally do not test other fluids/ substance: nails, hair, for the simple reason: it provides me no useful information. If blood measurements are made, it is especially critical to use exact reproducible timing post chelation. 45 minutes may be the optimal time (based on standard half times of GBCAs themselves, so 1/2 standard half time of 90 minutes, with a range of 30 minutes to 1 hour... But measurements must be near exact.

Combining serum Gd with urine Gd, may be an interesting measure to observe both the amount of Gd remobilized in the blood, and also concurrently eliminated in the urine.. I am not sure we need that now.

Right now:

I always like to see pre- and post chelation 24 hour urines as paired data. Nothing else right now makes enough sense to me to be worth the added expense.

The best available chelator should be used for the metal in question.

I am interested in decreasing total body content of the metal in question. This means being aware of the various tissues that have the metal deposited in them, and understanding removal from the durable reservoirs, especially if they are large. With Gd and lead the most durable large reservoir is bone. Decreasing total body content always requires multiple chelation sessions, and spacing between chelation. 3 weeks may be optimal in most, with a range of 1-4 weeks, based on specific nuances of the patient.

Richard Semelka, MD