Urine

Most toxic elements are eliminated at least in part, in the urine. For this reason, and due to the relative ease of collection, urine is commonly utilized for toxic element screening for persons with normal renal function. Urine is the specimen of choice for detecting exposure to aluminum, arsenic, cadmium, and mercury. For these elements, the extent of exposure is related to urine concentrations. Spot or random urine specimens are adequate for screening purposes, but because elimination of toxic elements can be multi-phasic, a 24-h urine collection is important for diagnostic purposes. Elemental concentrations in urine are often normalized to creatinine, a metabolic end product of creatine phosphate that is excreted at a relatively constant rate if individuals have normal renal function, to improve utility of serial specimens from the same patient or comparison of results between patients. Several reference intervals and toxic thresholds are based on creatinine-normalized values of toxic elements in urine (1-5). Urine can also be used to monitor elimination of toxic elements, particularly in conjunction with chelation therapy, a common decontamination strategy.

Falsely elevated results are often consequential to external contamination. The collection site is a considerable source of contamination, and as such, urine specimens should be collected away from the workplace or other areas that are likely to be contaminated. Guidelines on personal hygiene should also be followed, and smoking should be avoided throughout the collection and pre-analytical processes to minimize external contamination. The collection container is a potential source of external contamination as well. Rubber and colored dyes used in the manufacture of catheters or collection containers may contain cadmium or other elements that can leech into the sample. Even clear plastics contain some elements that may lead to a falsely elevated result (see Table 2). Unless tested to qualify as trace element free, preservative substances added to the urine collection should be considered a potential contamination source as well and should be avoided if possible (6-9).

Falsely low results may be consequential to loss of elements by adsorption to vial surfaces, volatilization, or precipitation. The use of urine preservatives such as hydrochloric or nitric acids has been used historically to prevent loss due to adhesion. However, the use of preservatives does not appear to be necessary for most elements if specimens are refrigerated and stored for up to 65 days (6). Both mercury and lead are considered "sticky" and are therefore vulnerable to "loss" by adhesion to the specimen container or other materials. Mercury loss is also possible through volatilization, possibly due to formation of volatile nitrates when nitric acid is used as a preservative or as part of the analytical setup. As a result, mercury testing methods often employ hydrochloric acid instead of nitric acid, or gold amalgamation with inductively-coupled plasma mass spectrometry (ICP-MS) or atomic absorption spectroscopy (AAS) (10,11). Figure 1 illustrates the loss of mercury from urine collected on day "zero" and tested at regular intervals for 65 days. In addition to elemental loss due to adhesion or volatilization, falsely low results may also occur consequential to the formation of

Table 2

Examples of Possible Sources of Contamination that may Contribute to Falsely Elevated Toxic

Element Results (6,9,10,12)

Table 2

Examples of Possible Sources of Contamination that may Contribute to Falsely Elevated Toxic

Element Results (6,9,10,12)

Toxic element

Possible sources

Aluminum

Plastic (PS, PC), serum or plasma separator gels, EDTA (blood

anticoagulant), boric acid (urine preservative), acids and reagents, ceiling

tiles, insulation, HEPA filters, skin

Arsenic

Boric acid and potassium pyrosulfate (urine preservatives), acids and

reagents, skin

Cadmium

Yellow or red-colored plastics, acids and reagents, skin

Iron

Plastic (PS), PVC tubing, Teflon, acids and reagents

Lead

Plastic (ETFE), heparin, acids and reagents, skin

Mercury

Analytical carryover

ETFE, ethylenetetrafluoroethylene; PC, polycarbonate; PS, polystyrene; PVC, polyvinyl chloride.

ETFE, ethylenetetrafluoroethylene; PC, polycarbonate; PS, polystyrene; PVC, polyvinyl chloride.

precipitate. Visible precipitate is common in urine, particularly after it has been refrigerated or when urine is obtained from a patient with an active urinary tract infection. Variability in analytical results has been shown with specimens containing arsenic or mercury, two toxic elements that concentrate in urine precipitates. If the laboratory removes the precipitate, such as through centrifugation of the specimen, results will be falsely low. If the specimens are not well mixed, inconsistent and erroneous results may be observed (6,10-12).

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