Test Catalog

Test ID: CKELR    
Creatine Kinase Isoenzyme Reflex, Serum

Useful For Suggests clinical disorders or settings where the test may be helpful

Detecting the macro forms of creatine kinase (CK)


Identifying the source of a CK elevation

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

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.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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 CK-MB is increased in acute myocardial infarction (AMI); however, CK-MB has been replaced by troponin as the preferred biomarker for the diagnosis of AMI.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.

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.



< or =3 months: not established

>3 months: 39-308 U/L


< or =3 months: not established

>3 months: 26-192 U/L

Reference values have not been established for patients that are less 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%

Interpretation Provides information to assist in interpretation of the test results

Creatine kinase (CK)-MB appears in serum 4 to 6 hours after the onset of pain in a myocardial infarction, peaks at 18 to 24 hours, and may persist for 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.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

In some patients, the presence of creatine kinase (CK)-MB is method dependent. 


CK-MB values that exceed 50% of the total CK probably reflect unusual B subunit synthesis since heart muscle rarely exceeds 30% MB.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Apple FS, Quist HE, Doyle PJ, et al: 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;4(10):194 doi:10.21037/atm.2016.05.19