Test ID: ADMA
Asymmetric Dimethylarginine, Plasma
Secondary ID 
A test code used for billing and in test definitions created prior to November 2011
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Useful For Suggests clinical disorders or settings where the test may be helpful
An adjunct to other risk markers for assessing an individual’s overall probabilistic likelihood of future coronary events, especially in patients with renal failure.
This test is best used to aid in eliciting lifestyle changes that can reduce risk of coronary events; it does not predict absolute events, nor does it predict specific events.
Method Name A short description of the method used to perform the test
Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Aliases Lists additional common names for a test, as an aid in searching
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Collection/Container/Tube: Lavender top (EDTA)
Submisson Container/Tube: Plastic vial
Specimen Volume: 1 mL
Collection Instructions: Fasting-overnight (12 hours)
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | Mild OK; Gross reject |
| Lipemia | Mild OK; Gross reject |
| Icterus | NA |
| Other | NA |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Plasma EDTA | Frozen (preferred) | |
| Ambient | 7 days | |
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
The conversion of arginine to nitric oxide (NO) is catalyzed by nitric oxide synthase (NOS), and asymmetric dimethylarginine (ADMA) is an inhibitor of that enzyme. When NO synthesis is blocked, a number of regulatory processes are immediately affected, including vasodilation, platelet aggregation, monocyte adhesion, and the inflammatory pathway, amongst others.
ADMA has been of interest in cardiovascular research for several years. Increased baseline plasma ADMA levels have been reported to be a predictor of outcomes in various studies including:
-In patients with acute coronary syndrome (ACS), 2 year follow up, the hazard ratio (HR) for all-cause mortality and for myocardial infarction (MI) was 2.45 and 2.28, respectively.(1) HR is the relative risk of an adverse event.
-In diabetics referred for coronary angiography, 2 year follow up, the HR for all-cause mortality and MI was 2.63 and 2.44, respectively.(2)
-In patients with unstable angina, 1 year follow up, ADMA persistently elevated was associated with increased cardiac events.(3)
-In nonsmoking males with a previous coronary event, 5 year follow up, 4-fold increase in risk of an adverse event.(4)
However, other studies have been inconclusive or found no association with cardiac events. Furthermore, the cardiac events may be up to 13 years or more in the future.
ADMA may be particularly important in assessing cardiovascular risk in the setting of renal failure. Patients with chronic renal failure have been shown to have increased ADMA concentrations compared to healthy controls. The elevated ADMA-associated inhibition of NO has been identified as a potential causal mechanism for the high mortality rates in patients with end-stage renal disease.(5,6)
The literature data must also be assessed with a cautionary eye to the methodology used, since the inactive isomer, symmetric dimethylarginine (SDMA), can contribute to the analytical result in some procedures. Our method measures ADMA without interference from SDMA.
It is important to consider the ADMA level in the context of all other biochemical parameters, whether it is a cardiac risk marker and/or a representation of an underlying disease process itself. The NOS pathway is involved in many physiological response mechanisms, and the ADMA levels measured in plasma samples reflect an integration of the contributions from all of them. Combinations of effects can blunt or reverse the predictive value of ADMA. Other risk factors, notably smoking, alter ADMA levels in a manner that reduces its predictive value for cardiac outcomes. In one study, ADMA levels were predictive of coronary events in nonsmokers, but not in smokers, where the levels were considerably lower. The underlying reason was postulated to be the upregulation of a key ADMA metabolizing enzyme by tobacco smoke, thus driving the plasma levels down.(7)
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
<18 years: not established
> or =18 years: 63-137 ng/mL
Interpretation Provides information to assist in interpretation of the test results
In patients with pre-existing coronary conditions or at high risk for coronary events (diabetes, renal insufficiency), asymmetric dimethylarginine (ADMA) levels in the upper tertile, >112 ng/mL, have an increased risk for future coronary events. The arginine value is considered only in some situations, when amino acid metabolism may be altered.
Reductions in ADMA are not known to be predictive of decreased risk of future coronary effects.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
The test has no value in patients who smoke. Elevated values should not be used to diagnose the presence of disease or events.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Cavusoglu E, Ruwende C, Chopra V, et al: Relationship of baseline plasma ADMA levels to cardiovascular outcomes at 2 years in men with acute coronary syndrome referred for coronary angiography. Coron Artery Dis 2009;20:112-117
2. Cavusoglu E, Ruwende C, Chopra V, et al: Relation of baseline plasma ADMA levels to cardiovascular morbidity and mortality at two years in men with diabetes mellitus referred for coronary angiography. Atherosclerosis. 2010 May;210(1):226-231
3. Krempl TK, Maas R, Sydow K, et al: Elevation of asymmetric dimethylarginine in patients with unstable angina and recurrent cardiovascular events. Eur Heart J 2005;26:1846-1851
4. Valkonen VP, Paiva H, Salonen JT, et al: Risk of acute coronary events and serum concentration of asymmetrical dimethylarginine. Lancet 2001;358:2127-2128
5. Ravani P, Tripepi G, Malberti F, et al: Asymmetrical dimethylarginine predicts progression to dialysis and death in patients with chronic kidney disease: a competing risks modeling approach. J Am Soc Nephrol 2005;16:2449-2455
6. Abedini S, Meinitzer A, Holme I, et al: Asymmetrical dimethylarginine is associated with renal and cardiovascular outcomes and all-cause mortality in renal transplant recipients. Kidney Int 2010 Jan;77(1):44-50
7. Maas R, Schulze F, Baumert J, et al: Asymmetric dimethylarginine, smoking, and risk of coronary heart disease in apparently healthy men: prospective analysis from the population-based Monitoring of Trends and Determinants in Cardiovascular Disease/Kooperative Gesundheitsforschung in der Region Augsburg study and experimental data. Clin Chem 2007 Apr;53(4):693-701
Method Description Describes how the test is performed and provides a method-specific reference
Asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and arginine (Arg) are separated and quantified by liquid chromatography-tandem mass spectrometry. C13-labeled ADMA and Arg internal standards (IS) are added to the samples and protein is precipitated using acetonitrile. A Cyclone MCX cation exchange turboflow column is used for sample clean-up, while a Waters Sunfire Silica analytical column is used for separation of ADMA, SDMA and Arg. From this column, the sample is transferred to an API 5000 tandem mass spectrometer (MS/MS) for instrumental analysis. The ratios of the extracted peak areas of ADMA and SDMA to C13(5)-ADMA and of Arg to C13(6)-Arg are used to calculate the concentration of the respective analytes present. SDMA is not reported, since it is analyzed only to ensure continuing separation from ADMA. (Unpublished Mayo method)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Wednesday; 8 a.m.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
83789
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
| Result ID | Reporting Name | LOINC Code |
|---|---|---|
| 83651 | Asymmetric Dimethyl Arginine, P | In Process |
| 32053 | ADMA Interpretation | In Process |
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