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Epic Code LAB1230733 Heavy Metal/Creatinine Ratio, with Reflex, Random, Urine

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Useful For

Preferred screening test for detection of arsenic, cadmium, mercury, and lead in random urine specimens

Specimen Type

Urine


Specimen Required


Patient Preparation:

-Patient should not eat seafood for a 48-hour period prior to start of collection.

-High concentrations of gadolinium and iodine are known to interfere with most metal tests. If either gadolinium- or iodine-containing contrast media has been administered, a specimen should not be collected for 96 hours.

Supplies: Urine Tubes, 10 mL (T068)

Collection Container/Tube: Clean, plastic urine container with no metal cap or glued insert

Submission Container/Tube: Plastic, 10-mL urine tube or clean, plastic aliquot container with no metal cap or glued insert

Specimen Volume: 6 mL

Collection Instructions:

1. Collect a random urine specimen.

2. See Metals Analysis Specimen Collection and Transport for complete instructions.


Specimen Minimum Volume

3 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Urine Refrigerated (preferred) 7 days
  Frozen  7 days

Reject Due To

  All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Day(s) Performed

Monday through Friday

Reference Values

ARSENIC/CREATININE:

0-17 years: Not established

≥18 years: <24 mcg/g creatinine

 

CADMIUM/CREATININE:

0-17 years: Not established

≥18 years: <0.6 mcg/g creatinine

 

MERCURY/CREATININE:

0-17 years: Not established

≥18 years: <2 mcg/g creatinine

 

LEAD/CREATININE:

0-17 years: Not established

≥18 years: <2 mcg/g creatinine

Clinical Information

Arsenic (As), lead (Pb), cadmium (Cd), and mercury (Hg) are well-known toxins, and toxic exposures are characterized by increased urinary excretion of these metals.

 

Arsenic is a naturally occurring element that is usually found in the environment combined with other elements such as oxygen, chlorine, and sulfur. Arsenic combined with these elements is called inorganic arsenic. Arsenic combined with carbon and hydrogen is referred to as organic arsenic. The organic forms (eg, arsenobetaine and arsenocholine) are relatively nontoxic, while the inorganic forms are toxic. The toxic inorganic forms are arsenite (As[3+]/As[III]) and arsenate (As[5+]/As[V]). Inorganic As(V) is readily reduced to inorganic As(III), which is then primarily broken down to the less toxic methylated metabolites monomethylarsonic acid and subsequently dimethylarsinic acid.

 

People are exposed to arsenic by eating food, drinking water, or breathing air. Of these, food is usually the largest source of arsenic. The predominant dietary source of arsenic is seafood, followed by rice/rice cereal, mushrooms, and poultry. While seafood contains the greatest amounts of arsenic, from fish and shellfish, this is mostly in an organic form of arsenic called arsenobetaine, which is much less harmful. Some seaweed may contain arsenic in the inorganic form, which is more toxic. In the United States, some areas also contain high natural levels of arsenic in rock, which can lead to elevated levels in the soil and drinking water. Occupational (eg, copper or lead smelting, wood treating, or pesticide application) exposure is another source where people may be introduced to elevated levels of arsenic. Lastly, hazardous waste sites may contain large quantities of arsenic and, if not disposed of properly, may get into the surrounding water, air, or soil.

 

A wide range of signs and symptoms may be seen in acute arsenic poisoning including headache, nausea, vomiting, diarrhea, abdominal pain, hypotension, fever, hemolysis, seizures, and mental status changes. Symptoms of chronic poisoning, also called arseniasis, are mostly insidious and nonspecific. The gastrointestinal tract, skin, and central nervous system are usually involved. Nausea, epigastric pain, colic abdominal pain, diarrhea, and paresthesias of the hands and feet can also occur.

 

Since arsenic is excreted predominantly by glomerular filtration, measurement of arsenic in urine is the most reliable means of detecting arsenic exposures within the last several days.

 

Arsenic toxicity affects a number of organ systems.

 

Lead toxicity primarily affects the gastrointestinal, neurologic, and hematopoietic systems.

 

Chronic exposure to cadmium causes accumulated kidney damage.

 

The correlation between the levels of mercury excretion in the urine and the clinical symptoms is considered poor.

Cautions

Consumption of seafood before collection of a urine specimen for arsenic testing is likely to result in a report of an elevated concentration of arsenic found in the urine, which can be clinically misleading.

 

Nitric acid cannot be added to either the collection or aliquot container. Nitrate interferes with the extraction procedure that would need to take place in the event of a positive arsenic result.

Interpretation

Arsenic:

Physiologically, arsenic exists in a number of toxic and nontoxic forms. The total arsenic concentration reflects all the arsenic present in the sample regardless of species (eg, inorganic vs. methylated vs. organic arsenic). The measurement of urinary total arsenic levels is generally accepted as the most reliable indicator of recent arsenic exposure. However, if the total urine arsenic concentration is elevated, arsenic speciation must be performed to identify if it is a toxic form (eg, inorganic and methylated forms) or a relatively nontoxic organic form (eg, arsenobetaine and arsenocholine).

 

The inorganic toxic forms of arsenic (eg, As[III] and As[V]) are found in the urine shortly after ingestion, whereas the less toxic methylated forms, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), are the species that predominate longer than 24 hours after ingestion. In general, urinary As(III) and As(V) concentrations peak in the urine at approximately 10 hours and return to normal 20 to 30 hours after ingestion. Urinary MMA and DMA concentrations normally peak at approximately 40 to 60 hours and return to baseline 6 to 20 days after ingestion.

 

This test can determine if a patient has been exposed to above-average levels of arsenic. It cannot predict whether the arsenic levels in their body will affect their health.

 

Cadmium:

Urine cadmium levels primarily reflect total body burden of cadmium. Cadmium excretion above 3.0 mcg/g creatinine indicates significant exposure to cadmium.

 

For occupational testing, OSHA cadmium standard is below 3.0 mcg/g creatinine, and the biological exposure index is 5 mcg/g creatinine.

 

Mercury:

The correlation between the levels of mercury (Hg) excretion in the urine and the clinical symptoms is considered poor.

 

Previous thought indicated urine as a more appropriate marker of inorganic mercury because organic mercury represented only a small fraction of urinary mercury. Based on possible demethylation of methylmercury within the body, urine may represent a mixture of dietary methylmercury and inorganic mercury. Seafood consumption can contribute to urinary mercury levels (up to 30%),(1) consistent with the suggestion that due to demethylation processes in the human body, a certain proportion of urinary mercury can originate from dietary consumption of fish/seafood.(2)

 

Lead:

Measurements of urinary lead levels have been used to assess lead exposure. However, like lead blood, urinary lead excretion mainly reflects recent exposure and thus shares many of the same limitations for assessing lead body burden or long-term exposure.(3,4)

 

Urinary lead concentration increases exponentially with blood lead and can exhibit relatively high intra-individual variability, even at similar blood lead concentrations.(5,6)

Reporting Name

Heavy Metal/Creat Ratio,w/Reflex,U

Method Name

ASCU, CDCU, HGCU, PBCU: Triple Quadrupole Inductively Coupled Plasma Mass Spectrometry (ICP-MS/MS)

CRETR: Enzymatic Colorimetric Assay

Method Description

The metal analytes of interest are analyzed by inductively coupled plasma mass spectrometry.(Unpublished Mayo method)

CPT Code Information

82175

82300

83825

83655

82570

LOINC Code Information

Test ID Test Order Name Order LOINC Value
HMUCR Heavy Metal/Creat Ratio,w/Reflex,U 29589-9

 

Result ID Test Result Name Result LOINC Value
608902 Cadmium/Creatinine Ratio, U 13471-8
608903 Mercury/Creatinine Ratio, U 13465-0
608904 Lead/Creatinine Ratio, U 13466-8
CRETR Creatinine, Random, U 2161-8
608900 Arsenic/Creatinine Ratio, U 13463-5
608901 Total Arsenic Concentration 5586-3

Report Available

2 to 4 days

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

Clinical Reference

1. Tratnik JS, Falnoga I, Mazej D, et al: Results of the first national human biomonitoring in Slovenia: Trace elements in men and lactating women, predictors of exposure and reference values. Int J Hyg Environ Health. 2019 Apr;222(3):563-582. doi: 10.1016/j.ijheh.2019.02.008

2. Sherman LS, Blum JD, Franzblau A, Basu N: New insights into biomarkers of human mercury exposure using naturally occurring mercury stable isotopes. Envrn Sci Technol. 2013 Apr 2;47(7):3403-3409. doi: 10.1021/es305250z

3. Sakai T: Biomarkers of lead exposure. Ind Health. 2000 Apr;38(2):127-142. doi: 10.2486/indhealth.38.127

4. Skerfving S: Biological monitoring of exposure to inorganic lead. In: Clarkson TW, Friberg L, Nordberg GF, Sager PR, eds. Biological Monitoring of Toxic Metals. Rochester Series on Environmental Toxicity. Springer; 1988:169-197

5. Gulson BL, Jameson CW, Mahaffey KR, et al: Relationships of lead in breast milk to lead in blood, urine, and diet of the infant and mother. Environ Health Perspect. 1998 Oct;106(10):667-667. doi: 10.1289/ehp.98106667

6. Skerfving S, Ahlgren L, Christoffersson JO: Metabolism of inorganic lead in man. Nutr Res 1985;Suppl 1:601-607

7. Fillol CC, Dor F, Labat L, et al: Urinary arsenic concentrations and speciation in residents living in an area with naturally contaminated soils. Sci Total Environ. 2010 Feb 1;408(5):1190-1194. doi: 10.1016/j.scitotenv.2009.11.046

8. Caldwell KL, Jones RL, Verdon CP, Jarrett JM, Caudill SP, Osterloh JD: Levels of urinary total and speciated arsenic in the US population: National Health and Nutrition Examination Survey 2003-2004. J Expo Sci Environ Epidemiol. 2009 Jan;19(1):59-68. doi: 10.1038/jes.2008.32

9. Lee R, Middleton D, Caldwell K, et al: A review of events that expose children to elemental mercury in the United States. Environ Health Perspect. 2009 Jun;117(6):871-878. doi: 10.1289/ehp.0800337

10. Kosnett MJ, Wedeen RP, Rotherberg SJ, et al: Recommendations for medical management of adult lead exposure. Environ Health Perspect. 2007 Mar;115(3):463-471. doi: 10.1289/ehp.9784

11. de Burbane C, Buchet JP, Leroyer A, et al: Renal and neurologic effects of cadmium, lead, mercury, and arsenic in children: evidence of early effects and multiple interactions at environmental exposure levels. Environ Health Perspect. 2006 Apr;114(4):584-590. doi: 10.1289/ehp.8202

12. Agency for Toxic Substances and Disease Registry: Toxicological profile for arsenic. US Department of Health and Human Services; 2007. Available at www.atsdr.cdc.gov/ToxProfiles/tp2.pdf

13. Bernhoft RA: Mercury toxicity and treatment: a review of the literature. J Environ Public Health. 2012;2012:460508. doi: 10.1155/2012/460508

14. Strathmann FG, Blum LM: Toxic elements. In: Rifai N, Chiu RWK, Young I, Burnham CD, Wittwer CT, eds. Tietz Textbook of Laboratory Medicine. 7th ed. Elsevier; 2023:chap 44

Profile Information

Test ID Reporting Name Available Separately Always Performed
ASCU Arsenic/Creatinine Ratio, U Yes, (order ASUCR) Yes
CDCU Cadmium/Creatinine Ratio, U Yes, (order CDUCR) Yes
HGCU Mercury/Creatinine Ratio, U Yes, (order HGUCR) Yes
PBCU Lead/Creatinine Ratio, U Yes, (order PBUCR) Yes
CRETR Creatinine, Random, U No Yes

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
SPAS Arsenic Speciation, Random, U Yes No