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Test ID: CKELR Creatine Kinase Isoenzyme Reflex, Serum

Reporting Name

Creatine Kinase Isoenzyme Reflex, S

Useful For

Detecting the macro forms of creatine kinase (CK)


Identifying the source of a CK elevation

Clinical Information

Creatine kinase (CK) activity is found in the cytoplasm of several human tissues; major sources of CK include skeletal muscle, myocardium, and the brain. Cytoplasmic CK isoenzymes are dimers of the subunits M and B (MM, MB, or BB). Brain tissue contains predominantly CK-BB (CK1). Skeletal muscle contains almost exclusively CK-MM (CK3). The myocardium contains approximately 30% of CK-MB (CK2), which has been called the "heart-specific" isoenzyme. CK-MB is increased in acute myocardial infarction (AMI); however, CK-MB has been replaced by troponin as the preferred biomarker for the diagnosis of AMI.


Mitochondrial CK, located at the outer surface of the inner mitochondrial membrane, has been suggested to catalyze the rate-limiting step of energy transfer from mitochondrial adenosine triphosphate (ATP) with the formation of creatine phosphatase (CP). The CP molecule, which is smaller in size than ATP, diffuses to target organelles in the cytoplasm where its energy is transferred to ATP by cytoplasmic CK. CK activity results in nonaerobic production of ATP in muscle tissues during work.


Macro CK refers to at least 2 forms of CK. Macro CK type I is an antibody-bound form of cytoplasmic CK. It migrates between CK-MM and CK-MB. Macro CK type II (mitochondrial CK) migrates slightly cathodic of CK-MM. Detection of macro forms of CK is the primary reason for electrophoresis of CK activity.


Creatine kinase (CK)-MB appears in serum 3 to 8 hours after the onset of pain in a myocardial infarction, peaks at around 20 hours, and returns to baseline at 72 hours.


CK-MB may also be elevated in cases of carbon monoxide poisoning, pulmonary embolism, hypothyroidism, crush injuries, and muscular dystrophy.


Extreme elevations of CK-MB can be associated with skeletal muscle cell turnover as in polymyositis and, to a lesser degree, in rhabdomyolysis, as seen in strenuous exercise, particularly in the conditioned athlete.


CK-BB can be elevated in patients with head injury, in neonates, and in some cancers such as prostate cancer and small cell carcinoma of the lung. It can also be elevated in other malignancies; however, the clinical usefulness of CK-BB as a tumor marker needs further investigation.


The presence of macro CK can explain an elevation of total CK. It does not rise and fall as rapidly as CK-MM and CK-MB in muscle injury.


Macro CK type II (mitochondrial CK) is rarely observed. It is only seen in acutely ill patients with malignancies and other severe illnesses with a high-associated mortality, such as liver disease and hypoxic injury.

Testing Algorithm

Testing begins with total creatine kinase analysis (CK). If the total CK activity is below 100 U/L, testing is complete.


If total CK activity is 100 U/L or greater, then isoenzyme electrophoresis (CKE) will be performed at an additional charge.

Profile Information

Test ID Reporting Name Available Separately Always Performed
CK Creatine Kinase (CK), S Yes Yes
CKER CK Isoenzyme Elec, Specimen Only No Yes

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
CKE CK Isoenzyme Electrophoresis, S No No

Report Available

1 to 8 days

Day(s) Performed

CK, total: Monday through Sunday

CK isoenzymes: Tuesday, Thursday

Clinical Reference

1. Apple FS, Quist HE, Doyle PJ, Otto AP, Murakami MM: Plasma 99th percentile reference limits for cardiac troponin and creatine kinase MB mass for use with European Society of Cardiology/American College of Cardiology consensus recommendations. Clin Chem. 2003 Aug;49(8):1331-1336

2. Danese E, Montagnana M: An historical approach to the diagnostic biomarkers of acute coronary syndrome. Ann Transl Med. 2016 May;4(10):194. doi:10.21037/atm.2016.05.19

3. John RV, Devasiya T, Nidheesh VR, et al: Cardiovascular biomarkers in body fluids: progress and prospects in optical sensors. Biophys Rev. 2022 Aug 18;14(4):1023-1050. doi: 10.1007/s12551-022-00990-2. PMID: 35996626; PMCID: PMC9386656

Method Name

CK: Photometric

CKE: Electrophoresis, Densitometry

Specimen Type


Ordering Guidance

This test is not appropriate for the detection of myocardial injury and should not be used for that purpose. For diagnosis of an acute myocardial infarction order TRPS / Troponin T, 5th Generation, Plasma.

Necessary Information

1. Patient's age and sex are required.

2. Include date and time of collection.

Specimen Required

Collection Container/Tube:

Preferred: Serum gel

Acceptable: Red top

Submission Container/Tube: Plastic vial

Specimen Volume: 2 mL

Collection Instructions:

1. Serum gel tubes should be centrifuged within 2 hours of collection.

2. Red-top tubes should be centrifuged and the serum aliquoted into a plastic vial within 2 hours of collection.

Specimen Minimum Volume

0.75 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Serum Refrigerated (preferred) 7 days
  Frozen  28 days

Reference Values



≤3 months: Not established

>3 months: 39-308 U/L


≤3 months: Not established

>3 months: 26-192 U/L

Reference values have not been established for patients who are younger than 3 months of age.

Note: Strenuous exercise or intramuscular injections may cause transient elevation of creatine kinase (CK).



MM: 100%

MB: 0%

BB: 0%

Test Classification

This test has been cleared, approved, or is exempt by the US Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.

CPT Code Information

82550-CK, total

82552-CK isoenzymes (If appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
CKELR Creatine Kinase Isoenzyme Reflex, S 2157-6


Result ID Test Result Name Result LOINC Value
CK Creatine Kinase (CK), S 2157-6
CKER CK Isoenzyme Elec, Specimen Only 31208-2
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