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Analytical Considerations in the Clinical Laboratory Assessment of Metals

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Abstract

The presence of metals in the environment is ubiquitous and humans are constantly being exposed to them. As such, a general concern exists about potential health consequences that result from the exposure to metals. The continued efforts of environmental scientists to measure metals in clinical specimens are important for defining the extent of human exposure to these chemicals. Laboratory methods to measure the concentration of metals in human blood or urine are available, and they can be used to assess the extent of human exposure to these chemicals. However, several considerations should be reviewed when requesting a laboratory measurement of metals because some factors can affect the test result or its interpretation. These considerations are discussed in this article and include pre-analytical, analytical, and post-analytical factors. Clinicians with this knowledge will be able to request these laboratory tests for their patients with enhanced confidence.

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Conflict of Interest

Wang, none; Caldwell, none; and Jones, none.

Author information

Authors and Affiliations

  1. Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, 4770 Buford Highway, Atlanta, GA, 30341, USA

    Richard Y. Wang, Kathleen L. Caldwell & Robert L. Jones

Authors
  1. Richard Y. Wang
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  2. Kathleen L. Caldwell
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  3. Robert L. Jones
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Corresponding author

Correspondence to Richard Y. Wang.

Additional information

The findings and conclusions in this paper are those of the authors and do not necessarily represent the views of Centers for Disease Control and Prevention.

Appendix

Appendix

Index of Individuality

The degree of individuality can be expressed as the index of individuality (II) [31], where II = (CVa2 + CVi2)1/2 / CVg and CVa, CVi, and CVg represent the analytical method, intra-individual, and inter-individual coefficient variations, respectively. The equation for II can be simplified to CVi / CVg when CVa contributes minimally to II.

The II for a laboratory test can vary depending on the analyte. For example, the II for serum iron (0.76) was found to be higher than that for serum creatinine (0.24) in a convenience sample of 853 survey participants aged 16 to 69 years who had two blood measurements that were at least 8 days apart [29]. In another study of 68 adult volunteers who had weekly blood measurements for 10 to 12 weeks, the II for 15 routine serum chemistries varied from 0.38 (total cholesterol in women greater than 30 years old) to 1.38 (serum sodium) when the analytical method coefficient variation was included in the calculation [28, 30].

A reference value based on a laboratory test result with a high degree of individuality (i.e., an index of individuality <0.6) is not sensitive to a change in the test result for a specific person [26, 31]. On the other hand, a reference value for a test result with a low degree of individuality (i.e., an index of individuality >1.4) is more useful than the former test to detect a change in a test result for a specific person. This circumstance occurs because the distribution of values from an individual will cover much of the distribution of values for the reference interval derived from the group of reference individuals. Thus, the intra- and inter-individuality of the laboratory test result needs to be considered when developing or using reference values.

The index of individuality for a laboratory test can be increased by stratifying the population into groups, which will enhance the usefulness of the test to monitor individuals. For example, the II for urinary creatinine (millimoles per day) collected by 24-h sampling at four weekly intervals over a period of 40 weeks for a group of seven men and eight women was 0.46 for the overall group, 1.42 for the women, and 1.83 for the men [27]. Thus, the reference value for urinary creatinine is more useful when it is determined for each sex than for a group containing both sexes.

Reference Change Value

If the reference value for a laboratory test is not sensitive to monitor for change in a specific person, then a clinically based fixed criteria or a reference change value can be used to evaluate for change in the test result for that person [32]. The reference change value is a method used to interpret a difference in measurements in a patient. The current test result is compared with the patient’s past results and not a population-based reference value. The reference change value determines the percent change between two values that is statistically significant based on a Z-score (Z-statistics). The reference change value (RCV%) is calculated as: RCV% = 1.414 × Z × (CVa2 + CVi2)1/2. Z represents the Z-score, which is determined by the desired level of confidence in the estimated value (a bidirectional Z = 1.96 for a 95 % probability or a false-positive rate of 5 %).

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Wang, R.Y., Caldwell, K.L. & Jones, R.L. Analytical Considerations in the Clinical Laboratory Assessment of Metals. J. Med. Toxicol. 10, 232–239 (2014). https://doi.org/10.1007/s13181-014-0381-8

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