Preferred specimen type for biomonitoring nickel exposure
|Test Id||Reporting Name||Available Separately||Always Performed|
|NIUC||Nickel/Creat Ratio, U||No||Yes|
|CRETR||Creatinine, Random, U||No||Yes|
CRETR: Enzymatic Colorimetric Assay
This test is preferred for the determination of nickel exposure, but serum concentrations can be used to verify an elevated urine concentration. For more information see NIS / Nickel, Serum.
Patient Preparation: High concentrations of gadolinium and iodine are known to interfere with most metal tests. If gadolinium- or iodine-containing contrast media has been administered, a specimen should not be collected for 96 hours.
Supplies: Urine Tubes, 10 mL (T068)
Container/Tube: Plastic, 10-mL urine tube or clean, plastic aliquot container with no metal cap or glued insert
Specimen Volume: 3 mL
1. Collect a random urine specimen
2. See Trace Metals Analysis Specimen Collection and Transport in Special Instructions for complete instructions.
|Specimen Type||Temperature||Time||Special Container|
|Urine||Refrigerated (preferred)||28 days|
Preferred specimen type for biomonitoring nickel exposure
Nickel (Ni) is a highly abundant element with a silvery-white appearance. Nickel is frequently combined with other metals to form alloys and is essential for the catalytic activity of some plant and bacterial enzymes but has no known role in humans. Most nickel is used to make stainless steel.
Nickel and its compounds have no characteristic odor or taste. Ni compounds are used for Ni plating, to color ceramics, to make some batteries, and as catalysts that increase the rate of chemical reactions. One of the most toxic Ni compounds is nickel carbonyl, Ni(CO)4, which is used as a catalyst in petroleum refining and in the plastics industry, is frequently employed in the production of metal alloys (which are popular for their anticorrosive and hardness properties), in nickel-cadmium rechargeable batteries, and is used as a catalyst in hydrogenation of oils. Ni(CO)4 is very toxic.
Occupational exposure to Ni occurs primarily via inhalation of Ni compounds. Inhalation of dust high in Ni content has been associated with development of lung and nasal cancer.
Food is the major source of exposure to Ni. Foods naturally high in Ni include chocolate, soybeans, nuts, and oatmeal. Individuals may also be exposed to Ni by breathing air, drinking water, or smoking tobacco containing nickel. Stainless steel and coins contain Ni. Some jewelry is plated with Ni or made from Ni alloys. Patients may be exposed to Ni in implanted devices including joint prostheses, sutures, clips, and screws made from Ni-containing alloys.
The most common harmful health effect of Ni in humans is an allergic reaction. Approximately 10% to 20% of the population is sensitive to it. The most serious harmful health effects from exposure to Ni, such as chronic bronchitis, reduced lung function, and cancer of the lung and nasal sinus, have occurred in people who have breathed dust containing certain Ni compounds while working in Ni refineries or Ni-processing plants. Urine is the specimen of choice for the determination of Ni exposure, but serum concentrations can be used to verify an elevated urine concentration.
Patients undergoing dialysis are exposed to Ni and accumulate Ni in blood and other organs; there appear to be no adverse health effects from this exposure. Hypernickelemia has been observed in patients undergoing renal dialysis. At the present time, this is considered to be an incidental finding as no correlation with toxic events has been identified. Routine monitoring of patients undergoing dialysis is currently not recommended.
0-17 years: not established
Males > or =18 years: <3.8 mcg/g creatinine
Females > or =18 years: <4.3 mcg/g creatinine
Reference values have not been established for patients less than 18 years of age.
Ni concentrations above 50 mcg/g creatinine are of concern, suggesting excessive exposure.
Hypernickelemia, in the absence of exposure, may be an incidental finding or could be due to specimen contamination.
Specimen collection procedures for nickel (Ni) require special collection containers, rigorous attention to ultraclean specimen collection and handling procedures, and analysis in an ultraclean facility. Unless all of these procedures are followed, increased urinary Ni results may be an incidental and misleading finding.
This test cannot determine the source compound (eg, Ni sulfate) responsible for the exposure.
1. Moreno ME, Acosta-Saavedra LC, Mez-Figueroa D, et al: Biomonitoring of metal in children living in a mine tailings zone in Southern Mexico: A pilot study. Int J Hyg Environ Health. 2010;213:252-258. doi: 10.1016/j.ijheh.2010.03.005.
2. Schulz C, Angerer J, Ewers U, Heudorf U, Wilhelm M, Human Biomonitoring Commission of the German Federal Environment Agency: Revised and new reference values for environmental pollutants in urine or blood of children in Germany derived from the German Environmental Survey on Children 2003-2006 (GerES IV). Int J Hyg Environ Health. 2009;212:637-647. doi: 10.1016/j.ijheh.2009.05.003.
3. US Department of Health and Human Services: Toxicological profile for nickel. Agency for Toxic Substances and Disease Registry. HHS; 2005. Accessed 03/2020. Available at: www.atsdr.cdc.gov/ToxProfiles/tp15.pdf
4. Rifai N, Horvath AR, Wittwer CT, eds: Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 6th ed. Elsevier; 2018
This assay is performed on an inductively coupled plasma-mass spectrometer. Calibrating standards and blanks are diluted with an aqueous acidic diluent containing internal standards. Quality control specimens and patient samples are diluted in an identical manner. The mass range from 1 amu to 263 amu is rapidly scanned multiple times and ion counts tabulated for each mass of interest. Instrument response is defined by the linear relationship of analyte concentration versus ion count ratio (analyte ion count/internal standard ion count). Analyte concentrations are derived by reading the ion count ratio for each mass of interest and determining the concentration from the response line.(Unpublished Mayo method)
The enzymatic method is based on the determination of sarcosine from creatinine with the aid of creatininase, creatinase, and sarcosine oxidase. The liberated hydrogen peroxide is measured via a modified Trinder reaction using a colorimetric indicator. Optimization of the buffer system and the colorimetric indicator enables the creatinine concentration to be quantified both precisely and specifically.(Package insert: Creatinine plus ver 2. Roche Diagnostics; V15.0, 03/2019)
This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.