American College of Medical Toxicology Position Statement on Post-Chelator Challenge Urinary Metal Testing
American College of Medical Toxicology
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American College of Medical Toxicology 10645 N. Tatum Blvd.
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Suite 200-111, Phoenix, AZ 85028, USA URL: www.acmt.net
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Heavy metals, such as lead and mercury, are ubiquitous in
the environment [13]. Exposure in human populations is
constantly occurring, and detectable levels of lead and
mercury are commonly found in blood and urine of
individuals who have no clinical signs or symptoms of toxicity
and may be considered background or reference values [1
5]. Although urine testing for various metals in an
appropriate clinical context, using proper and validated methods,
is common and accepted medical practice, the use of
postchallenge (a.k.a., post-provocation) urine metal testing,
wherein specimens are typically collected within 48 h of
chelation agent administration, is fraught with many
misunderstandings, pitfalls, and risks. The American College of
Medical Toxicology issues this position statement in
disapproval of the use of post-challenge urinary metal testing
in clinical practice and the use of such test results as an
indication for further administration of chelating agents.
In current evidence-based medical practice, urinary
testing is commonly used in the biomonitoring of exposure
to certain metals such as arsenic and inorganic mercury
and the severity of their associated toxicity. It is accepted
practice to conduct such testing, e.g., in exposed
individuals with clinical evidence of peripheral neuropathy, as long
as validated collection and analytical methods are employed
prior to, or after, a sufficiently long time interval (e.g., 3
5 days) following administration of a chelating agent, i.e.,
applied to non-challenge urine specimens, and the results
are compared to appropriate reference values [5, 6]. In some
non-evidence-based medical practices, however, assessment
of metal poisoning is frequently based on non-validated
postchallenge urine metal testing, which invites inappropriate
comparison to normal urine reference ranges [47].
Chelating agents such as dimercaptosuccinic acid
(DMSA), dimercaptopropanesulfonic acid (DMPS),
dimercaprol, and edetate calcium disodium (CaNa2EDTA) bind
metallic and metalloid elements and have been shown to
increase their elimination from the body. Chelating agents
have been found to mobilize metals in healthy individuals
who have a body burden considered normal for a standard
reference population, as well as in those who are determined
to have a high body burden of the same metallic species
[4, 811]. More specifically, urine specimens collected in
relatively close temporal proximity to administration of
chelating agents, i.e., post-challenge specimens, are expected
to have increased concentrations of metallic elements. This
includes elements, such as zinc, that are essential to normal
physiologic functions and maintenance of good health.
Normal reference values for non-challenge urine metal
test results vary among and within different populations.
Ranges for these values have been established in nationally
certified laboratories that meet proficiency standards for
urinary metal testing [5]. However, scientifically acceptable
normal reference values for post-challenge urine metal
testing have not been established [10]. In addition, scientific
investigation to date has failed to establish a valid correlation
between prior metal exposure and post-challenge test values
[10]. Despite the lack of scientific support to do so, it is also
a common practice of some laboratories and care providers
to provide or apply non-challenge normal reference values as
a comparative means of interpreting results of post-challenge
urine metal testing [5]. Currently, available scientific data do
not provide adequate support for the use of post-challenge
urine metal testing as an accurate or reliable means of
identifying individuals who would derive therapeutic benefit
from chelation.
Unfortunately, the practice of post-challenge urine metal
testing and its application to assessment of metal poisoning
often leads to unwarranted and prolonged oral and/or
intravenous administration of chelating agents, in response to the
results of serial post-challenge testing that remain elevated
above non-challenge reference values. Chelation therapy
based on such laboratory values, in addition to being of no
benefit to patient outcome, may actually prove harmful [5,
12]; catastrophic outcomes such as acute fatal hypocalcemia
have been reported following the improper use of a chelating
agent, edetate disodium (Na2EDTA) [13]. In addition, the
safer formulation of this agent, CaNa2EDTA, has been
demonstrated to increase urinary excretion of essential
minerals such as iron, copper, and zinc [8, 14]. There is
published experimental evidence that deleterious effects may
occur when chelation is applied in the absence of prior lead
exposure [15]. Other chelating agents such as DMSA and
DMPS may also increase the elimination of certain essential
elements, as well as (...truncated)