Test Id : CPAVP
Copeptin proAVP, Plasma
Useful For
Suggests clinical disorders or settings where the test may be helpful
Investigating the differential diagnosis for patients with water balance disorders, including diabetes insipidus, in conjunction with osmolality and hydration status
May aid in the evaluation of cardiovascular disease in conjunction with other cardiac markers
Method Name
A short description of the method used to perform the test
Immunofluorescent Assay
NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.
Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test
Specimen Type
Describes the specimen type validated for testing
Plasma EDTA
Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing
Patient Preparation: For water-deprivation testing, for at least 8 hours, the patient should fast and thirst (no liquids, including water, are allowed).
Collection Container/Tube: Lavender top (EDTA)
Submission Container/Tube: Plastic screw-top vial
Specimen Volume: 0.5 mL
Collection Information: Centrifuge and aliquot plasma into a plastic vial. Do not submit in original tube.
Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the testing laboratory. The minimum volume is sufficient for one attempt at testing.
0.3 mL
Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected
| Gross hemolysis | Reject |
| Gross lipemia | OK |
| Gross icterus | OK |
Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Plasma EDTA | Refrigerated (preferred) | 7 days | |
| Ambient | 7 days | ||
| Frozen | 30 days |
Useful For
Suggests clinical disorders or settings where the test may be helpful
Investigating the differential diagnosis for patients with water balance disorders, including diabetes insipidus, in conjunction with osmolality and hydration status
May aid in the evaluation of cardiovascular disease in conjunction with other cardiac markers
Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Arginine vasopressin (AVP) and copeptin (also known as copeptin proAVP or copeptin AVP) are derived from the same precursor peptide. Copeptin has been proposed as a more stable, potentially superior, surrogate marker of AVP in the assessment of water balance disorders. Unlike AVP, copeptin is stable in plasma. Both copeptin and AVP are responsive to osmotic stimuli and increase in response to water deprivation. In healthy subjects, water deprivation causes the plasma osmolality to rise above approximately 280 to 290 mOsmol/kg, leading to the release of AVP and copeptin into the circulation. Copeptin increases gradually with fasting and water deprivation and declines rapidly after intake of water and food.
Diabetes insipidus (DI) is characterized by the inability to appropriately concentrate urine in response to volume and osmolar stimuli. The main causes for DI are decreased AVP production (central DI) or decreased renal response to AVP (nephrogenic DI).
The determination of the underlying disease pathology in patients with polyuria and altered plasma osmolality is often difficult. Polyuria can be related to insufficient AVP (central DI), reduced sensitivity to AVP (nephrogenic DI), or excessive water intake. Measurement of plasma copeptin concentration has been shown to be useful in the investigation of these AVP-related disorders. Additionally, utilization of copeptin has been proposed in the assessment of syndrome of inappropriate antidiuretic.
Copeptin is also a marker of acute hemodynamic stress and has been reported to aid in the prognosis or diagnosis of several cardiac disorders, such as acute coronary syndrome, stable coronary artery disease, congestive heart failure, and acute ischemic stroke. Some studies have demonstrated that copeptin may improve prediction of mortality and heart disease outcome when combined with natriuretic peptides such as B-type natriuretic peptide (BNP) and N-terminal proBNP.
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.
Non-water deprived, non-fasting adults*: <13.1 pmol/L
Water deprived, fasting adults**: <15.2 pmol/L
Non-water deprived, non-fasting pediatric patients***: <14.5 pmol/L
Note:
*Keller T, Tzikas S, Zeller T, et al. Copeptin improves early diagnosis of acute myocardial infarction. J Am Coll Cardiol. 2010;55(19):2096-2106. doi:10.1016/j.jacc.2010.01.029
**Internal Mayo Clinic study
***Du JM, Sang G, Jiang CM, He XJ, Han Y. Relationship between plasma copeptin levels and complications of community-acquired pneumonia in preschool children. Peptides. 2013;45:61-65. doi:10.1016/j.peptides.2013.04.015
Interpretation
Provides information to assist in interpretation of the test results
While secreted in equimolar concentrations in conjunction with arginine vasopressin (AVP), measured plasma concentrations of copeptin do not correlate strongly with AVP concentrations due to in vivo and in vitro differences in stability. Copeptin is a more stable surrogate biomarker of AVP release. The clinical utility of copeptin of differentiating polyuria and water balance disorders has been demonstrated in a number of studies, when used in conjunction with osmolality and hydration status.
In a prospective clinical study, an algorithm was established based on patients with polyuria-polydipsia syndrome (n=55). A non-water deprived baseline copeptin concentration of 21.4 pmol/L or greater was found to be consistent with the presence of nephrogenic diabetes insipidus (DI). In a described algorithm,(1) patients with a copeptin concentrations of under 21.4 pmol/L and a copeptin cut-off of 4.9 pmol/L after fluid deprivation, was used to distinguish between complete or partial DI (<4.9 pmol/L) and primary polydipsia (> or =4.9 pmol/L).
Central DI may also be differentiated from nephrogenic DI by measuring copeptin during a stimulus for AVP release such as a water deprivation test. Copeptin concentrations obtained in the process of a water deprivation test can be difficult to interpret because of variation in water deprivation protocols. Patients with psychogenic polydipsia will either have a normal response to water deprivation or, in long-standing cases, show a pattern suggestive of mild nephrogenic DI. Expert consultation is recommended in these circumstances.
Although the water-deprivation test is considered the reference standard for the evaluation of DI, measurement of saline stimulated copeptin was shown to be more accurate than the water-deprivation test.(2) In this indirect water deprivation test with a cutoff of 4.9 pmol/L or less indicated central DI while a concentration greater than 4.9 pmol/L indicated primary polydipsia.
An elevated plasma copeptin AVP concentration in a hyponatremic patient may be indicative of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). However, copeptin determination alone is not typically sufficient to distinguish SIADH from other hyponatremic disorders.(3)
Elevations of plasma copeptin in patients with symptoms of heart failure may be prognostic of short- and long-term mortality. In patients with heart failure (HF) following a myocardial infarction, elevations in copeptin are associated with severity of HF and poorer prognosis.(4) In a cohort of patients with class III or IV HF, copeptin concentrations of 40 pmol/L or greater significantly increased the risk of death or need for cardiac transplantation. The combination of elevated copeptin and hyponatremia was an even stronger predictor of heart failure, independent of B-type natriuretic peptide (BNP) and cardiac troponin (cTn) concentrations.(5)
Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Sepsis, severe sepsis, septic shock, lower respiratory tract infections, chronic obstructive pulmonary disease, and cardiovascular diseases (eg, chronic heart failure) may increase copeptin concentrations.
Arginine vasopressin (AVP) receptor antagonist therapies and other diseases in which AVP has been shown to play an important pathophysiologic role may also increase copeptin concentration.
In some cases, bronchial carcinoma may lead to ectopic copeptin secretion.
Mixed forms of diabetes insipidus (DI) can exist, and both central and peripheral DI may be incomplete, complicating the interpretation of results.
In rare cases, some individuals can develop antibodies to mouse or other animal antibodies (often referred to as human anti-mouse antibodies [HAMA] or heterophile antibodies), which may cause interference in some immunoassays. Caution should be used in interpretation of results and the laboratory should be alerted if the result does not correlate with the clinical presentation.
Clinical Reference
Recommendations for in-depth reading of a clinical nature
1. Timper K, Fenske W, Kuhn F, et al. Diagnostic accuracy of copeptin in the differential diagnosis of the polyuria-polydipsia syndrome: A prospective multicenter study. J Clin Endocrinol Metab. 2015;100(6):2268-2274. doi:10.1210/jc.2014-4507
2. Fenske W, Refardt J, Chifu I, et al. A copeptin-based approach in the diagnosis of diabetes insipidus. N Engl J Med. 2018;379(5):428-439. doi:10.1056/NEJMoa1803760
3. Fenske W, Stork S, Blechschmidt A, Maier SGK, Morgenthaler NG, Allolio B. Copeptin in the differential diagnosis of hyponatremia. J Clin Endocrinol Metab. 2009;94(1):123-129. doi:10.1210/jc.2008-1426
4. Neuhold S, Huelsmann M, Strunk G, et al. Comparison of copeptin, B-type natriuretic peptide, and amino-terminal pro-B-type natriuretic peptide in patients with chronic heart failure: prediction of death at different stages of the disease. J Am Coll Cardiol. 2008;52(4):266-272. doi:10.1016/j.jacc.2008.03.050
5. Miller WL, Grill DE, Struck J, Jaffe AS. Association of hyponatremia and elevated copeptin with death and need for transplantation in ambulatory patients with chronic heart failure. Am J Cardiol. 2013;111(6):880-885. doi:10.1016/j.amjcard.2012.11.053
6. Morgenthaler NG, Struck J, Alonso C, Bergmann A. Assay for the measurement of copeptin, a stable peptide derived from the precursor of vasopressin. Clin Chem. 2006;52(1):112-119. doi:10.1373/clinchem.2005.060038
7. Mueller C, Mockel M, Giannitsis E, et al. Use of copeptin for rapid rule-out of acute myocardial infarction. Eur Heart J Acute Cardiovasc Care. 2018;7(6):570-576. doi:10.1177/2048872617710791
8. Maisel A, Mueller C, Neath SX, et al. Copeptin helps in the early detection of patients with acute myocardial infarction: primary results of the CHOPIN trial (copeptin helps in the early detection of patients with acute myocardial infarction). J Am Coll Cardiol. 2013;62(2):150-160. doi:10.1016/j.jacc.2013.04.011
9. Keller T, Tzikas S, Zeller T, et al. Copeptin improves early diagnosis of acute myocardial infarction. J Am Coll Cardiol. 2010;55(19):2096-2106. doi:10.1016/j.jacc.2010.01.029
10. Du JM, Sang G, Jiang CM, He XJ, Han Y. Relationship between plasma copeptin levels and complications of community-acquired pneumonia in preschool children. Peptides. 2013;45:61-65. doi:10.1016/j.peptides.2013.04.015
11. Donegan D, Bornhorst J, Van Gompel J, et al. Postsurgical utility of copeptin for the prediction of postoperative arginine vasopressin deficiency. J Neurosurg. 2023;140(5):1276-1284. doi:10.3171/2023.8.JNS23418
12. Choy KW, Wijeratne N, Chiang C, Don-Wauchope A. (2024). Copeptin as a surrogate marker for arginine vasopressin: analytical insights, current utility, and emerging applications. Critical Reviews in Clinical Laboratory Sciences, 1–21. doi:10.1080/10408363.2024.2383899
Method Description
Describes how the test is performed and provides a method-specific reference
Copeptin pro-arginine vasopressin (proAVP) is measured in this homogeneous automated immunofluorescent assay on the BRAHMS Kryptor Compact PLUS. The Kryptor Compact PLUS uses TRACE (time resolved amplified cryptate emission) technology based on a nonradioactive transfer of energy. This transfer occurs between 2 fluorescent tracers: the donor (europium cryptate) and the acceptor (XL707). In the Copeptin proAVP assay, a sheep polyclonal antibody against C-terminal proAVP is labeled with europium cryptate and a mouse monoclonal antibody against C-terminal proAVP is labeled with XL707. Copeptin is sandwiched between the 2 antibodies, bringing them into close proximity. When the antigen-antibody complex is excited with a nitrogen laser at 337 nm, some fluorescent energy is emitted at 620 nm and the rest is transferred to XL707. This energy is then emitted as fluorescence at 707 nm. A ratio of the energy emitted at 707 nm to that emitted at 620 nm (internal reference) is calculated for each sample. Signal intensity is proportional to the number of antigen-antibody complexes formed and, therefore, to antigen concentration.(Unpublished Mayo method)
PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information
Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.
Monday through Saturday
Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.
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
Indicates the location of the laboratory that performs the test
Fees :
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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 instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.
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.
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 Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
CPT codes are provided by the performing laboratory.
CPT codes are provided by the performing laboratory.
84588
LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.
| Test Id | Test Order Name | Order LOINC Value |
|---|---|---|
| CPAVP | Copeptin proAVP, P | 78987-5 |
| Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
|---|---|---|
| CPAVP | Copeptin proAVP, P | 78987-5 |