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  IN THIS Article
 ::  Abstract
 ::  Introduction
 ::  CK and its Isoen...
 ::  CK-MB Measuremen...
 ::  Causes of Falsel...
 ::  Prognostic Value...
 ::  Why %CK-MB is Be...
 ::  References

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Year : 2010  |  Volume : 56  |  Issue : 3  |  Page : 226-228

Clinically effective CK-MB reporting: How to do it?


1 Department of Clinical Biochemistry, Global Hospitals & Health City, Chennai, India
2 Department of Chemical Pathology, Guy's & St. Thomas Hospitals NHS Trust, London SE1 7EH, United Kingdom

Date of Submission26-Feb-2009
Date of Decision22-Nov-2009
Date of Acceptance23-May-2010
Date of Web Publication23-Aug-2010

Correspondence Address:
S Vivekanandan
Department of Clinical Biochemistry, Global Hospitals & Health City, Chennai
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0022-3859.68646

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 :: Abstract 

The clinical utility of measuring the Muscle Brain (MB) isoenzyme of creatine kinase (CK) in the diagnosis of myocardial injury is well established. CK/CK-MB measurement in combination or CK-MB alone is widely used and reporting the results of CK-MB in absolute unit is the common current practice. CK-MB is widely measured by "Immunoinhibition" in India, which gives falsely elevated CK-MB results in the following circumstances: Central nervous system damage, childbirth, macro CK-immunoglobulin complex, in patients with carcinoma of various organs, such as prostate carcinoma and other adenocarcinomas. But, reporting %CK-MB rather than the absolute CK-MB results assists in detection of macroCK (or CK variants), associated proliferative and autoimmune pathologies and their prognosis.


Keywords: Creatine kinase, %CK-MB, immunoinhibition, macroCK


How to cite this article:
Vivekanandan S, Swaminathan R. Clinically effective CK-MB reporting: How to do it?. J Postgrad Med 2010;56:226-8

How to cite this URL:
Vivekanandan S, Swaminathan R. Clinically effective CK-MB reporting: How to do it?. J Postgrad Med [serial online] 2010 [cited 2018 May 22];56:226-8. Available from: http://www.jpgmonline.com/text.asp?2010/56/3/226/68646



 :: Introduction Top


The clinical utility of measuring the muscle brain (MB) isoenzyme of creatine kinase (CK; EC 2.7.3.2) in the diagnosis of myocardial injury is well established. [1],[2],[3] Although cardiac troponins have been recommended to be the new laboratory standard for AMI diagnosis, CK and CK-MB measurements are useful in detecting myocardial infarction, particularly in places/circumstances where cardiac troponins (cTn) are not available/affordable/useful. [4] In many hospitals/laboratories in India, CK/CK-MB measurement in combination or CK-MB alone is widely used but it is the usual practice to report the results of CK-MB in absolute unit. The aim of this letter is to suggest that reporting CK-MB as a relative index (%CK-MB) is clinically superior and yields additional clinically useful information not only as a cardiac marker but also in revealing other systemic pathologies, rather than reporting absolute levels.


 :: CK and its Isoenzyme Distribution Top


CK is found in skeletal muscle, heart and the brain. It is formed of two subunits, M and B. From a combination of these subunits, three isoenzymes are possible - MM, BB and MB. MM is the predominant isoenzyme in the skeletal and the cardiac muscle. BB is mainly found in the brain. [5] MB isoenzyme is predominantly found in the heart muscle, consisting of about 15% of the total CK in this tissue. It is also present in the skeletal muscle, accounting for <1% of the total CK. [5]

Sometimes, CK in circulation can be found as a large molecular weight variant, which is called macro-CK (also called variant CK). There are two types of macro-CK - type 1 is complexed with immunoglobulin G (IgG) and is chiefly associated with autoimmune diseases and type 2 is an oligomer of mitochondrial CK. [5],[6]


 :: CK-MB Measurement Method Top


CK-MB is widely measured by "Immunoinhibition" in India. In this, the sample is incubated with an antibody against the "M" subunit and the residual CK activity is measured and multiplied by 2 to give the value for CK-MB activity. [7] Activity remaining after "M" inhibition is the result of the "B" subunit of MB and BB activity, although CK-BB is not normally detectable. [7],[8]


 :: Causes of Falsely High CK-MB Activity Top


The immunoinhibition method may give falsely elevated CK-MB results in the following circumstances:

1. If CK-BB is present in serum then a falsely elevated CK-MB result will follow. A very good example is that healthy infants and children have CK-BB values above-normal to that found in healthy adults and they have high CK-MB results. [9],[10]

2. Raised absolute CK and CK-MB results [along with traditional cardiac markers (AST, LDH)] observed in subjects following prolonged or strenuous exercise (such as marathon running). But, the relative index (%CKMB) remains normal, confirming that the rise in this isoenzyme originated from the skeletal muscle rather than from the cardiac muscle. [11],[12]

3. Falsely high CK-MB values by this method are observed in patients with macro CK: (e.g. patients with gastrointestinal disorders (with macro CK type 1), patients with neoplasms (may have macro CK type 2), CK-BB and dermatomyositis. [6] Each of these conditions may result in apparent elevations in the % CK-MB (more than 25%) activities and, if present in patients suspected of having an AMI, might cause clinical ambiguities. [6]

Among the atypical CK isoenzymes, CK-BB is a clearly defined and well-described entity. [6],[13],[14] The prevalence of macro-CK is about 1-6% in the western hospital population, [15] predominantly in women, and usually in the higher age groups (>60 years). [14] The most common cause of CK-BB elevations are central nervous system damage [16] and childbirth, and the macro-CK-immunoglobulin complex is particularly elevated in patients with carcinoma of various organs, such as prostate carcinoma and other adenocarcinomas. [6]

4. The skeletal muscle mostly contains CK-MM, but carries about 1% of CK-MB. A very high level of plasma CK activity due to skeletal muscle damage will show quite high absolute levels of CK-MB, but the relative index, i.e. %CK-MB, will still be <1% (more commonly seen during prolonged/strenuous exercise). [12]

An additional caveat of this assay is interference by "CK"-like activity (similar to creatinine-like substances interfering in Jaffe reaction) not inhibited by M antiserum and adenylate kinase (EC 2.7.4.3). [17]


 :: Prognostic Value of CK Variants Top


The presence of these variant CK isoenzymes has prognostic value, because macro CK type 1 is usually present in patients who develop cardiovascular or autoimmune processes, whereas macro-CK type 2 is most commonly found in patients with malignant proliferation. The prognostic utility of variant CK can be achieved only when %CK-MB is reported and if it is more than 25% and Not by CK-MB absolute result. [18] This proliferation-prognostic utility is achievable only by %CKMB and neither by absolute CK-MB nor by any other cardiac marker such as cardiac Troponins.


 :: Why %CK-MB is Better? Top


The single %CK-MB (relative index) is more specific than the single CK-MB absolute result for detecting AMI specificity (96.1 vs. 93.2), acute coronary syndrome (specificity, 96.3 vs. 93.3) and serious cardiac events (96.3 vs. 93.3). The %CK-MB has a higher positive predictive value for all three outcomes. Thus, CK-MB >25% suggests the need to use other reliable cardiac markers such as cTn to rule in/out cardiac pathology and also warrants to focus on other pathologies, as given above, for optimal clinical effectiveness. If used with the full knowledge of its limitation, single CK/CK-MB measurement by immunoinhibition and reporting as %CK-MB alone can reliably detect and prognosticate macro-CK. The current CK-MB kits (both local and international) neither mention this limitation nor offer any solution for this limitation. Hence, the reason, reporting %CK-MB, is clinically superior and yields additional clinically useful information.

 
 :: References Top

1.Alpert JS, Thygesen K, Antman E, Bassand JP. Myocardial infarction redefined: A consensus document of The Joint European Societyof Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol 2000;36:959-69.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]  
2.Collinson PO, Gaze DC, Morris F, Morris B, Price A, Goodacre S. Comparison of biomarker strategies for rapid rule out of myocardial infarction in the emergency department using ACC/ESC diagnostic criteria. Ann Clin Biochem 2006;43:273-80.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]  
3.Rajappa M, Sharma A. Biomarkers of cardiac injury: An update. Angiology 2005;56:677-91.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]  
4.Novack V, Jotkowitz AB, Cutlip D, Amit G, Liebermann N, Porath A. Transition from CK-MB to troponin did not improve the 1 year mortality of non-ST elevation acute coronary syndromes. Postgrad Med J 2008;84:50-5.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]  
5.Wu AH. Creatine kinase, isoenzyme and variants. In: Wu AH, editor. Cardiac markers. Totowa, New Jersey. Humana Press; 1998. p. 113-26.  Back to cited text no. 5      
6.Lee KN, Csako G, Bernhardt P, Elin RJ. Relevance of macro creatine kinase type 1 and type 2 isoenzymes to laboratory and clinical data. Clin Chem 1994;40:1278-83.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]  
7.Delahunty TJ, Foreback CC. Automated creatine kinase-MB estimation by immuno-inhibition: A clinical evaluation. Clin Chem 1980;26:568-72.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]  
8.Schwartz JG, Brown RW, McMahan CA, Gage CL, Herber SA. Clinical and analytical evaluation of different methods for measurement of creatine kinase isoenzyme MB. Clin Chem 1989;35:130-4.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]  
9.Cuestas RA Jr. Creatine kinase isoenzymes in high-risk infants. Pediatr Res 1980;14:935-8.  Back to cited text no. 9  [PUBMED]    
10.Wu AH, Herson VC, Bowers GN Jr. Macro creatine kinase types 1 and 2: Clinical significance in neonates and children as compared with adults. Clin Chem 1983;29:201-4.  Back to cited text no. 10  [PUBMED]  [FULLTEXT]  
11.Brancaccio P, Mafulla N, Limongel FM. Creatine kinase monitoring in sports medicine. Br Med Bull 2007;81-82:209-30.  Back to cited text no. 11      
12.Redelmeier DA, Greenwald JA. Competing risks of mortality with marathons: Retrospective analysis. BMJ 2007;335:1275-7.  Back to cited text no. 12  [PUBMED]  [FULLTEXT]  
13.Ruiz Gines MA, Calafell Mas MF, Ruiz Gines JA, Fernandez Rodriquez E. Macro creatine kinase: Illness marker. Practical guide for the management. An Med Interna 2006;23:272-5.  Back to cited text no. 13      
14.Laureys M, Sion JP, Slabbynck H, Steensaens L, Cobbaert C, Derde MP, et al. Macromolecular creatine kinase type 1: A serum marker associated with disease. Clin Chem 1991;37:430-4.  Back to cited text no. 14      
15.Stein W, Bohner J, Renn W, Maulbetsch R. Macro creatine kinase type 2: Results of a prospective study in hospitalized patients. Clin Chem 1985;31:1959-64.  Back to cited text no. 15  [PUBMED]  [FULLTEXT]  
16.Pfeiffer FE, Homburger HA, Yanagihara T. Creatine kinase BB isoenzyme in CSF in neurologic disease. Measurement by radioimmunoassay. Arch Neurol 1983;40:169-72.  Back to cited text no. 16  [PUBMED]  [FULLTEXT]  
17.Yucel M, Tokalak I, Kulaksύzoπlu S, Arat Z. CK-MB activity and hemolysis: Where the interference begins? Turk J Biochem 2005;30:216-9.  Back to cited text no. 17      
18.Bruns DE. Diagnosis of acute myocardial infarction when skeletal muscle damage is present: A caveat regarding use of creatine kinase isoenzymes. Clin Chem 1989;35:705.  Back to cited text no. 18  [PUBMED]  [FULLTEXT]  



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2004 - Journal of Postgraduate Medicine
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