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If you require further information please refer to the full Method Sheet PDF under the given link, or contact your local Roche country representative." }, "Chapters": [ { "Name": "IntendedUse", "Value": "

Intended use

In vitro test for the quantitative determination of creatine kinase (CK) in human serum and plasma on cobas c systems.

", "Language": "en" }, { "Name": "TestPrinciple", "Value": "

Test principle

UV‑test

Creatine phosphate + ADP

CK

creatine + ATP

ATP + D‑glucose

HK

ADP + G6P

G6P + NADP+

G6PDH

D‑6‑phosphogluconate + NADPH + H+

Equimolar quantities of NADPH and ATP are formed at the same rate. The photometrically measured rate of formation of NADPH is directly proportional to the CK activity.

", "Language": "en" }, { "Name": "MeasuringRange", "Value": "

Limits and ranges

Measuring range

7‑2000 U/L (0.12‑33.4 µkat/L)

Determine samples having higher activities via the rerun function. Dilution of samples via the rerun function is a 1:11 dilution. Results from samples diluted by the rerun function are automatically multiplied by a factor of 11.

Lower limits of measurement

Limit of Blank, Limit of Detection and Limit of Quantitation

Limit of Blank

= 7 U/L (0.12 µkat/L)

Limit of Detection

= 7 U/L (0.12 µkat/L)

Limit of Quantitation

= 7 U/L (0.12 µkat/L)

The Limit of Blank, Limit of Detection and Limit of Quantitation were determined in accordance with the CLSI (Clinical and Laboratory Standards Institute) EP17‑A2 requirements.

The Limit of Blank is the 95th percentile value from n ≥ 60 measurements of analyte‑free samples over several independent series. The Limit of Blank corresponds to the concentration below which analyte‑free samples are found with a probability of 95 %.

The Limit of Detection is determined based on the Limit of Blank and the standard deviation of low concentration samples. The Limit of Detection corresponds to the lowest analyte concentration which can be detected (value above the limit of blank with a probability of 95 %).
The Limit of Quantitation is the lowest analyte concentration that can be reproducibly measured with a precision of 20 % CV. It has been determined using low concentration creatine kinase samples.

", "Language": "en" }, { "Name": "ExpectedValues", "Value": "

Expected values

Reference intervals strongly depend on the patient group and the specific clinical situation.

For healthy people, according to Klein et al.:

LREFKlein G, Berger A, Bertholf R, et al. Abstract: Multicenter Evaluation of Liquid Reagents for CK, CK-MB and LDH with Determination of Reference Intervals on Hitachi Systems. Clin Chem 2001;47:Suppl. A30.

CK

U/L

µkat/L

Men

39‑308

0.65‑5.14

Women

26‑192

0.43‑3.21

Consensus values:

LREFThomas L, Müller M, Schumann G, et al. Consensus of DGKL and VDGH for interim reference intervals on enzymes in serum. J Lab Med 2005; 29(5):301-308.

CK

U/L

µkat/L

Men

< 190

< 3.20

Women

< 170

< 2.85

Consensus values:

LREFThomas L, Müller M, Schumann G, et al. Consensus of DGKL and VDGH for interim reference intervals on enzymes in serum. J Lab Med 2005; 29(5):301-308.

CK‑MB

U/L

µkat/L

Men/women

< 25

< 0.42

Myocardial infarction: There is a high probability of myocardial damage when the following three conditions are fulfilled:

LREFStein W. Strategie der klinischen-chemischen Diagnostik des frischen Myokardinfarktes. Med Welt 1985;36:572-577.

U/L

µkat/L

1

CKmen

> 190

> 3.17

CKwomen

> 167

> 2.79

2

CK‑MB

> 24

> 0.40

3

The CK‑MB activity accounts for 6‑25 % of the total CK‑activity.

According to Tietz:

LREFWu AHB, editor. Tietz Clinical Guide to Laboratory Tests, 4th edition. St. Louis (MO): Saunders Elsevier 2006;306-307.

CK

U/L

µkat/L

Adult males > 19 years

20‑200

0.33‑3.34

Adult females > 19 years

20‑180

0.33‑3.01

The reference values according to Klein et al. are based on the 95th percentile of a group of healthy persons (202 men and 217 women) not involved in high‑intensity athletic activities.

In order to ensure high sensitivity in the diagnosis of heart diseases the values given by Tietz are recommended. The loss of diagnostic specificity thereby incurred can be compensated for by additionally determining CK‑MB and/or troponin T. When myocardial infarction is suspected the diagnostic strategy proposals in the consensus document of European and American cardiologists should in general be followed.

LREFMyocardial Infarction Redefined - A Consensus Document of the Joint European Society of Cardiology/ American College of Cardiology Committee for the Redefinition of Myocardial Infarction. Eur Heart J 2000;21:1502-1513.

If despite the suspicion of myocardial infarction the values found remain below the stated limits, a fresh infarction may be involved. In such cases, the determinations should be repeated after 4 hours.

CK varies with physical activity level and race in healthy individuals.

LREFWu AHB, editor. Tietz Clinical Guide to Laboratory Tests, 4th edition. St. Louis (MO): Saunders Elsevier 2006;306-307.
,
LREFBlack HR, Quallich H, Gareleck CB. Racial differences in serum creatine kinase levels. Am J Med 1986;81:479-487.

Each laboratory should investigate the transferability of the expected values to its own patient population and if necessary determine its own reference ranges.

", "Language": "en" }, { "Name": "LimitationInterference", "Value": "

Limitations - interference

Criterion: Recovery within ± 10 % of initial value at a creatine kinase activity of 140 U/L (2.34 µkat/L).

Icterus:

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an I index of 60 for conjugated and unconjugated bilirubin (approximate conjugated and unconjugated bilirubin concentration: 1026 µmol/L or 60 mg/dL).

Hemolysis:

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an H index of 100 (approximate hemoglobin concentration: 62.1 µmol/L or 100 mg/dL). The level of interference may be variable depending on the exact content of erythrocytes.

Lipemia (Intralipid):

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an L index of 1000. There is poor correlation between the L index (corresponds to turbidity) and triglycerides concentration. Highly lipemic specimens (L index > 1000) may cause high absorbance flagging.

Drugs: No interference was found at therapeutic concentrations using common drug panels.

LREFBreuer J. Report on the Symposium "Drug effects in Clinical Chemistry Methods". Eur J Clin Chem Clin Biochem 1996;34:385-386.
,
LREFSonntag O, Scholer A. Drug interference in clinical chemistry: recommendation of drugs and their concentrations to be used in drug interference studies. Ann Clin Biochem 2001;38:376-385.

Cyanokit (Hydroxocobalamin) at therapeutic concentrations interferes with the test.

In very rare cases, gammopathy, in particular type IgM (Waldenström’s macroglobulinemia), may cause unreliable results.

LREFBakker AJ, Mücke M. Gammopathy interference in clinical chemistry assays: mechanisms, detection and prevention. Clin Chem Lab Med 2007;45(9):1240-1243.

For diagnostic purposes, the results should always be assessed in conjunction with the patient’s medical history, clinical examination and other findings.

ACTION REQUIRED
Special Wash Programming: The use of special wash steps is mandatory when certain test combinations are run together on cobas c systems. The latest version of the carry‑over evasion list can be found with the NaOHD-SMS-SmpCln1+2-SCCS Method Sheets. For further instructions refer to the operator’s manual. cobas c 502 analyzer: All special wash programming necessary for avoiding carry‑over is available via the cobas link, manual input is required in certain cases.

Where required, special wash/carry‑over evasion programming must be implemented prior to reporting results with this test.

", "Language": "en" }, { "Name": "OrderInformation", "Value": "

OrderInformation (CC Reagents - cobas + Integra)

Order information

Analyzer(s) on which cobas c pack(s) can be used

07190794190

Creatine Kinase (200 tests)

System-ID 07 7485 5

 cobas c 311, cobas c 501/502

Materials required (but not provided):

10759350190

Calibrator f.a.s. (12 x 3 mL)

Code 401

10759350360

Calibrator f.a.s. (12 x 3 mL, for USA)

Code 401

12149435122

Precinorm U plus (10 x 3 mL)

Code 300

12149435160

Precinorm U plus (10 x 3 mL, for USA)

Code 300

12149443122

Precipath U plus (10 x 3 mL)

Code 301

12149443160

Precipath U plus (10 x 3 mL, for USA)

Code 301

05117003190

PreciControl ClinChem Multi 1 (20 x 5 mL)

Code 391

05947626190

PreciControl ClinChem Multi 1 (4 x 5 mL)

Code 391

05947626160

PreciControl ClinChem Multi 1 (4 x 5 mL, for USA)

Code 391

05117216190

PreciControl ClinChem Multi 2 (20 x 5 mL)

Code 392

05947774190

PreciControl ClinChem Multi 2 (4 x 5 mL)

Code 392

05947774160

PreciControl ClinChem Multi 2 (4 x 5 mL, for USA)

Code 392

04489357190

Diluent NaCl 9 % (50 mL)

System-ID 07 6869 3

", "Language": "en" }, { "Name": "SystemInformation", "Value": "

System information

For cobas c 311/501 analyzers:
CK2: ACN 550
For cobas c 502 analyzer:
CK2: ACN 8550

", "Language": "en" }, { "Name": "Handling", "Value": "

Reagent handling

Ready for use

", "Language": "en" }, { "Name": "TestDefinition", "Value": "

Application for serum and plasma

cobas c 311 test definition

Assay type

Rate A

Reaction time / Assay points

10 / 16‑29

Wavelength (sub/main)

546/340 nm

Reaction direction

Increase

Units

U/L (µkat/L)

Reagent pipetting

Diluent (H2O)

R1

100 µL

R2

20 µL

Sample volumes

Sample

Sample dilution

Sample

Diluent (NaCl)

Normal

2.8 µL

Decreased

2.8 µL

15 µL

150 µL

Increased

2.8 µL

cobas c 501 test definition

Assay type

Rate A

Reaction time / Assay points

10 / 24‑44

Wavelength (sub/main)

546/340 nm

Reaction direction

Increase

Units

U/L (µkat/L)

Reagent pipetting

Diluent (H2O)

R1

100 µL

R2

20 µL

Sample volumes

Sample

Sample dilution

Sample

Diluent (NaCl)

Normal

2.8 µL

Decreased

2.8 µL

15 µL

150 µL

Increased

2.8 µL

cobas c 502 test definition

Assay type

Rate A

Reaction time / Assay points

10 / 24‑44

Wavelength (sub/main)

546/340 nm

Reaction direction

Increase

Units

U/L (µkat/L)

Reagent pipetting

Diluent (H2O)

R1

100 µL

R2

20 µL

Sample volumes

Sample

Sample dilution

Sample

Diluent (NaCl)

Normal

2.8 µL

Decreased

2.8 µL

15 µL

150 µL

Increased

5.6 µL

", "Language": "en" }, { "Name": "StorageStability", "Value": "

Storage and stability

CK

Shelf life at 2‑8 °C:

See expiration date on cobas c pack label.

On‑board in use and refrigerated on the analyzer:

8 weeks

Diluent NaCl 9 %

Shelf life at 2‑8 °C:

See expiration date on cobas c pack label.

On‑board in use and refrigerated on the analyzer:

12 weeks

", "Language": "en" }, { "Name": "Calibration", "Value": "

Calibration

Calibrators

S1: H2O

S2: C.f.a.s.

Calibration mode

Linear

Calibration frequency

2‑point calibration
• after reagent lot change
• as required following quality control procedures

Traceability: This method has been standardized against the IFCC Method for Creatine Kinase.

LREFSchumann G, Bonora R, Ceriotti F, et al. IFCC Primary Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes at 37 °C – Part 2. Reference Procedure for the Measurement of Catalytic Concentration of Creatine Kinase. Clin Chem Lab Med 2002;40(6):635-642.

", "Language": "en" }, { "Name": "Limitations", "Value": "", "Language": "en" }, { "Name": "PerformanceData", "Value": "

Specific performance data

Representative performance data on the analyzers are given below. Results obtained in individual laboratories may differ.

", "Language": "en" }, { "Name": "Precision", "Value": "

Precision

Repeatability and intermediate precision were determined using human samples and controls in accordance with the CLSI (Clinical and Laboratory Standards Institute) EP5 requirements (2 aliquots per run, 2 runs per day, 21 days). The following results were obtained:

Repeatability

Mean

U/L (µkat/L)

SD

U/L (µkat/L)

CV

%

Human serum 1

18.7 (0.31)

0.6 (0.01)

3.0

Human serum 2

137 (2.29)

0.8 (0.01)

0.6

Human serum 3

477 (7.97)

3.0 (0.05)

0.6

Human serum 4

946 (15.8)

5.3 (0.09)

0.6

Human serum 5

1816 (30.3)

9.4 (0.16)

0.5

PCCC Multi 1*

154 (2.57)

0.9 (0.02)

0.6

PCCC Multi 2

301 (5.02)

1.3 (0.02)

0.4

Intermediate precision

Mean

U/L (µkat/L)

SD

U/L (µkat/L)

CV

%

Human serum 1

18.7 (0.31)

0.6 (0.01)

3.2

Human serum 2

137 (2.29)

1.1 (0.02)

0.8

Human serum 3

477 (7.97)

3.1 (0.05)

0.6

Human serum 4

946 (15.8)

5.8 (0.10)

0.6

Human serum 5

1816 (30.3)

10 (0.17)

0.6

PCCC Multi 1

154 (2.57)

1.7 (0.03)

1.1

PCCC Multi 2

301 (5.02)

2.6 (0.04)

0.9

*PCCC = PreciControl ClinChem

The data obtained on cobas c 501 analyzer(s) are representative for cobas c 311 analyzer(s).

", "Language": "en" }, { "Name": "MethodComparison", "Value": "

Method comparison

Creatine kinase values for human serum and plasma samples obtained on a cobas c 501 analyzer (y) were compared with those determined using the CKL reagent on a COBAS INTEGRA 800 analyzer (x).

Sample size (n) = 132

Passing/Bablok

LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790.

Linear regression

y = 1.021x + 5.88 U/L

y = 1.006x + 13.6 U/L

τ = 0.980

r = 0.999

The sample activities were between 7.59 and 1946 U/L (0.13 and 32.5 µkat/L).

The data obtained on cobas c 501 analyzer(s) are representative for cobas c 311 analyzer(s).

", "Language": "en" }, { "Name": "Summary", "Value": "

Summary

Creatine kinase (CK) is a dimeric enzyme occurring in four different forms: a mitochondrial isoenzyme and the cytosolic isoenzymes CK‑MM (skeletal muscle type), CK‑BB (brain type) and CK‑MB (myocardial type).

LREFThomas L, ed. Labor und Diagnose, 8th ed. Bd 1:TH-Books Verlagsgesellschaft 2012.

The determination of CK and CK‑isoenzyme activities is utilized in the diagnosis and monitoring of myocardial infarction and myopathies such as the progressive Duchenne muscular dystrophy. Following injury to the myocardium, such as occurs with acute myocardial infarction

LREFThomas L, ed. Labor und Diagnose, 8th ed. Bd 1:TH-Books Verlagsgesellschaft 2012.
, CK is released from the damaged myocardial cells. In early cases, a rise in the CK‑activity can be found just 4 hours after an infarction.
LREFThomas L, ed. Labor und Diagnose, 8th ed. Bd 1:TH-Books Verlagsgesellschaft 2012.
,
LREFStein W. Laboratory Diagnosis of Acute Myocardial Infarction. Darmstadt: GIT Verlag 1988;34-37.
The CK activity reaches a maximum after 12‑24 hours and then falls back to the normal range after 3‑4 days.
LREFThomas L, ed. Labor und Diagnose, 8th ed. Bd 1:TH-Books Verlagsgesellschaft 2012.
,
LREFStein W. Laboratory Diagnosis of Acute Myocardial Infarction. Darmstadt: GIT Verlag 1988;34-37.

The assay method using creatine phosphate and ADP was first described by Oliver

LREFOliver IT. A spectrophotometric method for the determination of creatine phosphokinase and myokinase. Biochem J 1955;61:116-122.
, modified by Rosalki
LREFRosalki SB. An improved procedure for serum creatine phosphokinase determination. J Lab Clin Med 1967;69:696-705.
and further improved for optimal test conditions by Szasz et al.
LREFSzasz G, Gruber W, Bernt E. Creatine kinase in serum: 1. Determination of optimum reaction conditions. Clin Chem 1976;22(5):650-656.
CK is rapidly inactivated by oxidation of the sulfhydryl groups in the active center. The enzyme can be reactivated by the addition of acetylcysteine (NAC).
LREFSzasz G, Gruber W, Bernt E. Creatine kinase in serum: 1. Determination of optimum reaction conditions. Clin Chem 1976;22(5):650-656.
Interference by adenylate kinase is prevented by the addition of diadenosine pentaphosphate
LREFStandard method for the determination of creatine kinase activity. J Clin Chem Clin Biochem 1977;15:249-260.
and AMP.
LREFSzasz G, Gruber W, Bernt E. Creatine kinase in serum: 1. Determination of optimum reaction conditions. Clin Chem 1976;22(5):650-656.
,
LREFStandard method for the determination of creatine kinase activity. J Clin Chem Clin Biochem 1977;15:249-260.

Standardized methods for the determination of CK with activation by NAC were recommended by the German Society for Clinical Chemistry (DGKC)

LREFStandard method for the determination of creatine kinase activity. J Clin Chem Clin Biochem 1977;15:249-260.
in 1977 and the International Federation of Clinical Chemistry (IFCC)
LREFHørder M, Elser RC, Gerhardt M, et al. Approved Recommendation on IFCC Methods for the Measurement of Catalytic Concentration of Enzymes. Part 7. IFCC Method for Creatine Kinase. Eur J Clin Chem Clin Biochem 1991;29:435-456.
in 1991. In 2002 the IFCC confirmed their recommendation and extended it to 37 °C.
LREFSchumann G, Bonora R, Ceriotti F, et al. IFCC Primary Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes at 37 °C – Part 2. Reference Procedure for the Measurement of Catalytic Concentration of Creatine Kinase. Clin Chem Lab Med 2002;40(6):635-642.
,
LREFKlauke R, Schmidt E, Lorentz K. Recommendations for carrying out standard ECCLS procedures (1988) for the catalytic concentrations of creatine kinase, aspartate aminotransferase, alanine aminotransferase and γ-glutamyltransferase at 37 °C. Eur J Clin Chem Clin Biochem 1993;31:901-909.
The method described here is derived from the formulation recommended by the IFCC and was optimized for performance and stability.

", "Language": "en" }, { "Name": "Reagents", "Value": "

Reagents - working solutions

R1

Imidazole buffer: 123 mmol/L, pH 6.5 (37 °C); EDTA: 2.46 mmol/L; Mg2+: 12.3 mmol/L; ADP: 2.46 mmol/L; AMP: 6.14 mmol/L; diadenosine pentaphosphate: 19 µmol/L; NADP+ (yeast): 2.46 mmol/L; N‑acetylcysteine: 24.6 mmol/L; HK (yeast): ≥ 36.7 µkat/L; G6PDH (E. coli): ≥ 23.4 µkat/L; preservative; stabilizers; additives.

R2

CAPSO* buffer: 20 mmol/L, pH 8.8 (37 °C); glucose: 120 mmol/L; EDTA: 2.46 mmol/L; creatine phosphate: 184 mmol/L; preservative; stabilizers.

*CAPSO: 3‑(cyclohexylamine)‑2‑hydroxy‑1‑propanesulfonic acid

R1 is in position B and R2 is in position C.

", "Language": "en" }, { "Name": "PrecautionsWarnings", "Value": "

Precautions and warnings

For in vitro diagnostic use for health care professionals. Exercise the normal precautions required for handling all laboratory reagents.

Infectious or microbial waste:
Warning: handle waste as potentially biohazardous material. Dispose of waste according to accepted laboratory instructions and procedures.

Environmental hazards:
Apply all relevant local disposal regulations to determine the safe disposal.

Safety data sheet available for professional user on request.

For USA: Caution: Federal law restricts this device to sale by or on the order of a physician.

This kit contains components classified as follows in accordance with the Regulation (EC) No. 1272/2008:

Danger

H360D

May damage the unborn child.

Prevention:

P201

Obtain special instructions before use.

P202

Do not handle until all safety precautions have been read and understood.

P280

Wear protective gloves/ protective clothing/ eye protection/ face protection/ hearing protection.

Response:

P308 + P313

IF exposed or concerned: Get medical advice/attention.

Storage:

P405

Store locked up.

Disposal:

P501

Dispose of contents/container to an approved waste disposal plant.

Product safety labeling follows EU GHS guidance.

Contact phone: all countries: +49-621-7590, USA: 1-800-428-2336

", "Language": "en" }, { "Name": "Caution", "Value": "", "Language": "en" }, { "Name": "QualityControl", "Value": "

Quality control

For quality control, use control materials as listed in the \"Order information\" section.

In addition, other suitable control material can be used.

The control intervals and limits should be adapted to each laboratory’s individual requirements. Values obtained should fall within the defined limits. Each laboratory should establish corrective measures to be taken if values fall outside the defined limits.

Follow the applicable government regulations and local guidelines for quality control.

", "Language": "en" }, { "Name": "SpecimenPreparation", "Value": "

Specimen collection and preparation

For specimen collection and preparation only use suitable tubes or collection containers.

Only the specimens listed below were tested and found acceptable.
Serum: Nonhemolyzed serum is the specimen of choice and also recommended by IFCC.
Plasma: Li‑heparin, K2‑, K3‑EDTA plasma.

Please note: Differences in the degree of hemolysis resulting from the blood sampling procedure used can lead to deviating results in serum and plasma.

The sample types listed were tested with a selection of sample collection tubes that were commercially available at the time of testing, i.e. not all available tubes of all manufacturers were tested. Sample collection systems from various manufacturers may contain differing materials which could affect the test results in some cases. When processing samples in primary tubes (sample collection systems), follow the instructions of the tube manufacturer.

Centrifuge samples containing precipitates before performing the assay.

Stability in serum:

LREFGuder WG, Narayanan S, Wisser H, et al. List of Analytes; Preanalytical Variables. Brochure in: Samples: From the Patient to the Laboratory. Darmstadt: GIT-Verlag 1996.

2 days at 20‑25 °C

7 days at 4‑8 °C

4 weeks at -20 °C

Stability in EDTA/heparin plasma:

LREFData on file at Roche Diagnostics.

2 days at 15‑25 °C

7 days at 2‑8 °C

4 weeks at (-15)‑(-25) °C

", "Language": "en" } ] } }, { "ProductSpecVariant": { "MetaData": { "DocumentMaterialNumber": "0007190794190COIN", "ProductName": "CK", "ProductLongName": "Creatine Kinase", "Language": "en", "DocumentVersion": "3", "DocumentObjectID": "FF0000000595D10E", "DocumentOriginID": "FF0000000170D00E", "MaterialNumbers": [ "07190794190" ], "InstrumentReferences": [ { "ID": "302", "BrandName": "COBAS INTEGRA 400 plus" } ], "DisclaimerText": "Product information shown on this page contains elements of the officially released Method Sheet. If you require further information please refer to the full Method Sheet PDF under the given link, or contact your local Roche country representative." }, "Chapters": [ { "Name": "IntendedUse", "Value": "

Intended use

In vitro test for the quantitative determination of creatine kinase (CK) in human serum and plasma on COBAS INTEGRA systems.

", "Language": "en" }, { "Name": "TestPrinciple", "Value": "

Test principle

UV‑test

Creatine phosphate + ADP

CK

creatine + ATP

ATP + D‑glucose

HK

ADP + G6P

G6P + NADP+

G6PDH

D‑6‑phosphogluconate + NADPH + H+

Equimolar quantities of NADPH and ATP are formed at the same rate. The photometrically measured rate of formation of NADPH is directly proportional to the CK activity.

", "Language": "en" }, { "Name": "MeasuringRange", "Value": "

Limits and ranges

Measuring range

7‑2000 U/L (0.12‑33.4 µkat/L)

Determine samples having higher activities via the rerun function. Dilution of samples via the rerun function is a 1:11 dilution. Results from samples diluted by the rerun function are automatically multiplied by a factor of 11.

Lower limits of measurement

Limit of Blank, Limit of Detection and Limit of Quantitation

Limit of Blank

= 7 U/L (0.12 µkat/L)

Limit of Detection

= 7 U/L (0.12 µkat/L)

Limit of Quantitation

= 7 U/L (0.12 µkat/L)

The Limit of Blank, Limit of Detection and Limit of Quantitation were determined in accordance with the CLSI (Clinical and Laboratory Standards Institute) EP17‑A2 requirements.

The Limit of Blank is the 95th percentile value from n ≥ 60 measurements of analyte‑free samples over several independent series. The Limit of Blank corresponds to the concentration below which analyte‑free samples are found with a probability of 95 %.

The Limit of Detection is determined based on the Limit of Blank and the standard deviation of low concentration samples. The Limit of Detection corresponds to the lowest analyte concentration which can be detected (value above the limit of blank with a probability of 95 %).
The Limit of Quantitation is the lowest analyte concentration that can be reproducibly measured with a precision of 20 % CV. It has been determined using low concentration creatine kinase samples.

", "Language": "en" }, { "Name": "ExpectedValues", "Value": "

Expected values

Reference intervals strongly depend on the patient group and the specific clinical situation.

For healthy people, according to Klein et al.:

LREFKlein G, Berger A, Bertholf R, et al. Abstract: Multicenter Evaluation of Liquid Reagents for CK, CK-MB and LDH with Determination of Reference Intervals on Hitachi Systems. Clin Chem 2001;47:Suppl. A30.

CK

U/L

µkat/L

Men

39‑308

0.65‑5.14

Women

26‑192

0.43‑3.21

Consensus values:

LREFThomas L, Müller M, Schumann G, et al. Consensus of DGKL and VDGH for interim reference intervals on enzymes in serum. J Lab Med 2005; 29(5):301-308.

CK

U/L

µkat/L

Men

< 190

< 3.20

Women

< 170

< 2.85

Consensus values:

LREFThomas L, Müller M, Schumann G, et al. Consensus of DGKL and VDGH for interim reference intervals on enzymes in serum. J Lab Med 2005; 29(5):301-308.

CK‑MB

U/L

µkat/L

Men/women

< 25

< 0.42

Myocardial infarction: There is a high probability of myocardial damage when the following three conditions are fulfilled:

LREFStein W. Strategie der klinischen-chemischen Diagnostik des frischen Myokardinfarktes. Med Welt 1985;36:572-577.

U/L

µkat/L

1

CKmen

> 190

> 3.17

CKwomen

> 167

> 2.79

2

CK‑MB

> 24

> 0.40

3

The CK‑MB activity accounts for 6‑25 % of the total CK‑activity.

According to Tietz:

LREFWu AHB, editor. Tietz Clinical Guide to Laboratory Tests, 4th edition. St. Louis (MO): Saunders Elsevier 2006;306-307.

CK

U/L

µkat/L

Adult males > 19 years

20‑200

0.33‑3.34

Adult females > 19 years

20‑180

0.33‑3.01

The reference values according to Klein et al. are based on the 95th percentile of a group of healthy persons (202 men and 217 women) not involved in high‑intensity athletic activities.

In order to ensure high sensitivity in the diagnosis of heart diseases the values given by Tietz are recommended. The loss of diagnostic specificity thereby incurred can be compensated for by additionally determining CK‑MB and/or troponin T. When myocardial infarction is suspected the diagnostic strategy proposals in the consensus document of European and American cardiologists should in general be followed.

LREFMyocardial Infarction Redefined - A Consensus Document of the Joint European Society of Cardiology/ American College of Cardiology Committee for the Redefinition of Myocardial Infarction. Eur Heart J 2000;21:1502-1513.

If despite the suspicion of myocardial infarction the values found remain below the stated limits, a fresh infarction may be involved. In such cases, the determinations should be repeated after 4 hours.

CK varies with physical activity level and race in healthy individuals.

LREFWu AHB, editor. Tietz Clinical Guide to Laboratory Tests, 4th edition. St. Louis (MO): Saunders Elsevier 2006;306-307.
,
LREFBlack HR, Quallich H, Gareleck CB. Racial differences in serum creatine kinase levels. Am J Med 1986;81:479-487.

Each laboratory should investigate the transferability of the expected values to its own patient population and if necessary determine its own reference ranges.

", "Language": "en" }, { "Name": "LimitationInterference", "Value": "

Limitations - interference

Criterion: Recovery within ± 10 % of initial value at a creatine kinase activity of 140 U/L (2.34 µkat/L).

Icterus:

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an I index of 60 for conjugated and unconjugated bilirubin (approximate conjugated and unconjugated bilirubin concentration: 1026 µmol/L or 60 mg/dL).

Hemolysis:

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an H index of 100 (approximate hemoglobin concentration: 62.1 µmol/L or 100 mg/dL). The level of interference may be variable depending on the exact content of erythrocytes.

Lipemia (Intralipid):

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an L index of 1000. There is poor correlation between the L index (corresponds to turbidity) and triglycerides concentration. Highly lipemic specimens (L index > 1000) may cause high absorbance flagging.

Drugs: No interference was found at therapeutic concentrations using common drug panels.

LREFBreuer J. Report on the Symposium "Drug effects in Clinical Chemistry Methods". Eur J Clin Chem Clin Biochem 1996;34:385-386.
,
LREFSonntag O, Scholer A. Drug interference in clinical chemistry: recommendation of drugs and their concentrations to be used in drug interference studies. Ann Clin Biochem 2001;38:376-385.

Cyanokit (Hydroxocobalamin) at therapeutic concentrations interferes with the test.

In very rare cases, gammopathy, in particular type IgM (Waldenström’s macroglobulinemia), may cause unreliable results.

LREFBakker AJ, Mücke M. Gammopathy interference in clinical chemistry assays: mechanisms, detection and prevention. Clin Chem Lab Med 2007;45(9):1240-1243.

For diagnostic purposes, the results should always be assessed in conjunction with the patient’s medical history, clinical examination and other findings.

ACTION REQUIRED
Special Wash Programming: The use of special wash steps is mandatory when certain test combinations are run together on COBAS INTEGRA analyzers. Refer to the CLEAN Method Sheet for further instructions and for the latest version of the Extra wash cycle list.
Where required, special wash/carry-over evasion programming must be implemented prior to reporting results with this test.

", "Language": "en" }, { "Name": "OrderInformation", "Value": "

OrderInformation (CC Reagents - cobas + Integra)

Order information

Analyzer(s) on which cobas c pack(s) can be used

07190794190

Creatine Kinase (200 tests)

System-ID 07 7485 5

COBAS INTEGRA 400 plus

Materials required (but not provided):

10759350190

Calibrator f.a.s. (12 x 3 mL)

System-ID 07 3718 6

10759350360

Calibrator f.a.s. (12 x 3 mL, for USA)

System-ID 07 3718 6

12149435122

Precinorm U plus (10 x 3 mL)

System-ID 07 7999 7

12149435160

Precinorm U plus (10 x 3 mL, for USA)

System-ID 07 7999 7

12149443122

Precipath U plus (10 x 3 mL)

System-ID 07 8000 6

12149443160

Precipath U plus (10 x 3 mL, for USA)

System-ID 07 8000 6

05117003190

PreciControl ClinChem Multi 1 (20 x 5 mL)

System-ID 07 7469 3

05947626190

PreciControl ClinChem Multi 1 (4 x 5 mL)

System-ID 07 7469 3

05947626160

PreciControl ClinChem Multi 1 (4 x 5 mL, for USA)

System-ID 07 7469 3

05117216190

PreciControl ClinChem Multi 2 (20 x 5 mL)

System-ID 07 7470 7

05947774190

PreciControl ClinChem Multi 2 (4 x 5 mL)

System-ID 07 7470 7

05947774160

PreciControl ClinChem Multi 2 (4 x 5 mL, for USA)

System-ID 07 7470 7

20756350322

NaCl Diluent 9 % (6 x 22 mL)

System-ID 07 5635 0

", "Language": "en" }, { "Name": "SystemInformation", "Value": "

System information

Test CK2, test ID 0-045

", "Language": "en" }, { "Name": "Handling", "Value": "

Reagent handling

Ready for use

", "Language": "en" }, { "Name": "TestDefinition", "Value": "

Application for serum and plasma

Test definition

Measuring mode

Absorbance

Abs. calculation mode

Kinsearch

Reaction mode

R1‑S‑SR

Reaction direction

Increase

Wavelength A/B

340/552 nm

Calc. first/last

10/45‑62

Unit

U/L

Pipetting parameters

Diluent (H2O)

R1

100 µL

-

Sample

2.75 µL

2 µL

SR

20 µL

-

Total volume

124.75 µL

", "Language": "en" }, { "Name": "StorageStability", "Value": "

Storage and stability

Shelf life at 2‑8 °C

See expiration date on cobas c pack label

On-board in use at 10‑15 °C

8 weeks

", "Language": "en" }, { "Name": "Calibration", "Value": "

Calibration

Calibrator

Calibrator f.a.s.

Use deionized water as zero calibrator.

Calibration mode

Linear regression

Calibration replicate

Duplicate recommended

Calibration interval

Each lot and as required following quality control procedures

Traceability: This method has been standardized against the IFCC Method for Creatine Kinase.

LREFSchumann G, Bonora R, Ceriotti F, et al. IFCC Primary Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes at 37 °C – Part 2. Reference Procedure for the Measurement of Catalytic Concentration of Creatine Kinase. Clin Chem Lab Med 2002;40(6):635-642.

", "Language": "en" }, { "Name": "Limitations", "Value": "", "Language": "en" }, { "Name": "PerformanceData", "Value": "

Specific performance data

Representative performance data on the COBAS INTEGRA analyzers are given below. Results obtained in individual laboratories may differ.

", "Language": "en" }, { "Name": "Precision", "Value": "

Precision

Repeatability and intermediate precision were determined using human samples and controls in accordance with the CLSI (Clinical and Laboratory Standards Institute) EP5 requirements (2 aliquots per run, 2 runs per day, 21 days). The following results were obtained:

Repeatability

Mean

U/L (µkat/L)

SD

U/L (µkat/L)

CV

%

Human serum 1

22.1 (0.37)

0.9 (0.01)

3.9

Human serum 2

144 (2.40)

1.4 (0.02)

1.0

Human serum 3

494 (8.25)

4.6 (0.08)

0.9

Human serum 4

980 (16.4)

10 (0.2)

1.0

Human serum 5

1893 (31.6)

19 (0.3)

1.0

PCCC Multi 1*

162 (2.71)

1.5 (0.03)

0.9

PCCC Multi 2

311 (5.19)

2.9 (0.05)

0.9

Intermediate precision

Mean

U/L (µkat/L)

SD

U/L (µkat/L)

CV

%

Human serum 1

22.2 (0.37)

1.0 (0.02)

4.6

Human serum 2

145 (2.42)

1.9 (0.03)

1.3

Human serum 3

498 (8.31)

5.7 (0.10)

1.1

Human serum 4

980 (16.4)

12 (0.19)

1.2

Human serum 5

1893 (31.6)

22 (0.36)

1.1

PCCC Multi 1*

161 (2.69)

2.0 (0.03)

1.3

PCCC Multi 2

309 (5.16)

3.6 (0.06)

1.2

*PCCC = PreciControl ClinChem

", "Language": "en" }, { "Name": "MethodComparison", "Value": "

Method comparison

Creatine kinase values for human serum and plasma samples obtained on a COBAS INTEGRA 400 plus analyzer (y) were compared with those determined using the CKL reagent on a COBAS INTEGRA 800 analyzer (x).

Sample size (n) = 109

Passing/Bablok

LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790.

Linear regression

y = 0.999x + 12.5 U/L

y = 0.987x + 19.7 U/L

τ = 0.980

r = 0.999

The sample activities were between 11.7 and 1819 U/L (0.20 and 30.4 µkat/L).

", "Language": "en" }, { "Name": "Summary", "Value": "

Summary

Creatine kinase (CK) is a dimeric enzyme occurring in four different forms: a mitochondrial isoenzyme and the cytosolic isoenzymes CK‑MM (skeletal muscle type), CK‑BB (brain type) and CK‑MB (myocardial type).

LREFThomas L, ed. Labor und Diagnose, 8th ed. Bd 1:TH-Books Verlagsgesellschaft 2012.

The determination of CK and CK‑isoenzyme activities is utilized in the diagnosis and monitoring of myocardial infarction and myopathies such as the progressive Duchenne muscular dystrophy. Following injury to the myocardium, such as occurs with acute myocardial infarction

LREFThomas L, ed. Labor und Diagnose, 8th ed. Bd 1:TH-Books Verlagsgesellschaft 2012.
, CK is released from the damaged myocardial cells. In early cases, a rise in the CK activity can be found just 4 hours after an infarction.
LREFThomas L, ed. Labor und Diagnose, 8th ed. Bd 1:TH-Books Verlagsgesellschaft 2012.
,
LREFStein W. Laboratory Diagnosis of Acute Myocardial Infarction. Darmstadt: GIT Verlag 1988;34-37.
The CK‑activity reaches a maximum after 12‑24 hours and then falls back to the normal range after 3‑4 days.
LREFThomas L, ed. Labor und Diagnose, 8th ed. Bd 1:TH-Books Verlagsgesellschaft 2012.
,
LREFStein W. Laboratory Diagnosis of Acute Myocardial Infarction. Darmstadt: GIT Verlag 1988;34-37.

The assay method using creatine phosphate and ADP was first described by Oliver

LREFOliver IT. A spectrophotometric method for the determination of creatine phosphokinase and myokinase. Biochem J 1955;61:116-122.
, modified by Rosalki
LREFRosalki SB. An improved procedure for serum creatine phosphokinase determination. J Lab Clin Med 1967;69:696-705.
and further improved for optimal test conditions by Szasz et al.
LREFSzasz G, Gruber W, Bernt E. Creatine kinase in serum: 1. Determination of optimum reaction conditions. Clin Chem 1976;22(5):650-656.
CK is rapidly inactivated by oxidation of the sulfhydryl groups in the active center. The enzyme can be reactivated by the addition of acetylcysteine (NAC).
LREFSzasz G, Gruber W, Bernt E. Creatine kinase in serum: 1. Determination of optimum reaction conditions. Clin Chem 1976;22(5):650-656.
Interference by adenylate kinase is prevented by the addition of diadenosine pentaphosphate
LREFStandard method for the determination of creatine kinase activity. J Clin Chem Clin Biochem 1977;15:249-260.
and AMP.
LREFSzasz G, Gruber W, Bernt E. Creatine kinase in serum: 1. Determination of optimum reaction conditions. Clin Chem 1976;22(5):650-656.
,
LREFStandard method for the determination of creatine kinase activity. J Clin Chem Clin Biochem 1977;15:249-260.

Standardized methods for the determination of CK with activation by NAC were recommended by the German Society for Clinical Chemistry (DGKC)

LREFStandard method for the determination of creatine kinase activity. J Clin Chem Clin Biochem 1977;15:249-260.
in 1977 and the International Federation of Clinical Chemistry (IFCC)
LREFHørder M, Elser RC, Gerhardt M, et al. Approved Recommendation on IFCC Methods for the Measurement of Catalytic Concentration of Enzymes. Part 7. IFCC Method for Creatine Kinase. Eur J Clin Chem Clin Biochem 1991;29:435-456.
in 1991. In 2002 the IFCC confirmed their recommendation and extended it to 37 °C.
LREFSchumann G, Bonora R, Ceriotti F, et al. IFCC Primary Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes at 37 °C – Part 2. Reference Procedure for the Measurement of Catalytic Concentration of Creatine Kinase. Clin Chem Lab Med 2002;40(6):635-642.
,
LREFKlauke R, Schmidt E, Lorentz K. Recommendations for carrying out standard ECCLS procedures (1988) for the catalytic concentrations of creatine kinase, aspartate aminotransferase, alanine aminotransferase and γ-glutamyltransferase at 37 °C. Eur J Clin Chem Clin Biochem 1993;31:901-909.
The method described here is derived from the formulation recommended by the IFCC and was optimized for performance and stability.

", "Language": "en" }, { "Name": "Reagents", "Value": "

Reagents - working solutions

R1

Imidazole buffer: 123 mmol/L, pH 6.5 (37 °C); EDTA: 2.46 mmol/L; Mg2+: 12.3 mmol/L; ADP: 2.46 mmol/L; AMP: 6.14 mmol/L; diadenosine pentaphosphate: 19 µmol/L; NADP+ (yeast): 2.46 mmol/L; N‑acetylcysteine: 24.6 mmol/L; HK (yeast): ≥ 36.7 µkat/L; G6PDH (E. coli): ≥ 23.4 µkat/L; preservative; stabilizers; additives.

SR

CAPSO* buffer: 20 mmol/L, pH 8.8 (37 °C); glucose: 120 mmol/L; EDTA: 2.46 mmol/L; creatine phosphate: 184 mmol/L; preservative; stabilizers.

*CAPSO: 3‑(cyclohexylamine)‑2‑hydroxy‑1‑propanesulfonic acid

R1 is in position B and SR is in position C.

", "Language": "en" }, { "Name": "PrecautionsWarnings", "Value": "

Precautions and warnings

For in vitro diagnostic use for health care professionals. Exercise the normal precautions required for handling all laboratory reagents.

Infectious or microbial waste:
Warning: handle waste as potentially biohazardous material. Dispose of waste according to accepted laboratory instructions and procedures.

Environmental hazards:
Apply all relevant local disposal regulations to determine the safe disposal.

Safety data sheet available for professional user on request.

For USA: Caution: Federal law restricts this device to sale by or on the order of a physician.

This kit contains components classified as follows in accordance with the Regulation (EC) No. 1272/2008:

Danger

H360D

May damage the unborn child.

Prevention:

P201

Obtain special instructions before use.

P202

Do not handle until all safety precautions have been read and understood.

P280

Wear protective gloves/ protective clothing/ eye protection/ face protection/ hearing protection.

Response:

P308 + P313

IF exposed or concerned: Get medical advice/attention.

Storage:

P405

Store locked up.

Disposal:

P501

Dispose of contents/container to an approved waste disposal plant.

Product safety labeling follows EU GHS guidance.

Contact phone: all countries: +49-621-7590, USA: 1-800-428-2336

", "Language": "en" }, { "Name": "Caution", "Value": "", "Language": "en" }, { "Name": "QualityControl", "Value": "

Quality control

Reference range

Precinorm U, Precinorm U plus, Precinorm CK‑MB or PreciControl ClinChem Multi 1

Pathological range

Precipath U, Precipath U plus, Precipath CK‑MB* or PreciControl ClinChem Multi 2

Control interval

24 hours recommended

Control sequence

User defined

Control after calibration

Recommended

*Not for use in the US

For quality control, use control materials as listed in the “Order information” section. In addition, other suitable control material can be used.

The control intervals and limits should be adapted to each laboratory’s individual requirements. Values obtained should fall within the defined limits. Each laboratory should establish corrective measures to be taken if values fall outside the defined limits.

Follow the applicable government regulations and local guidelines for quality control.

", "Language": "en" }, { "Name": "SpecimenPreparation", "Value": "

Specimen collection and preparation

For specimen collection and preparation only use suitable tubes or collection containers.

Only the specimens listed below were tested and found acceptable.
Serum: Nonhemolyzed serum is the specimen of choice and also recommended by IFCC.
Plasma: Li‑heparin, K2‑, K3‑EDTA plasma.

Please note: Differences in the degree of hemolysis resulting from the blood sampling procedure used can lead to deviating results in serum and plasma.

The sample types listed were tested with a selection of sample collection tubes that were commercially available at the time of testing, i.e. not all available tubes of all manufacturers were tested. Sample collection systems from various manufacturers may contain differing materials which could affect the test results in some cases. When processing samples in primary tubes (sample collection systems), follow the instructions of the tube manufacturer.

Centrifuge samples containing precipitates before performing the assay.

Stability in serum:

LREFGuder WG, Narayanan S, Wisser H, et al. List of Analytes; Preanalytical Variables. Brochure in: Samples: From the Patient to the Laboratory. Darmstadt: GIT-Verlag 1996.

2 days at 20‑25 °C

7 days at 4‑8 °C

4 weeks at -20 °C

Stability in EDTA/heparin plasma:

LREFData on file at Roche Diagnostics.

2 days at 15‑25 °C

7 days at 2‑8 °C

4 weeks at (-15)‑(-25) °C

", "Language": "en" } ] } }, { "ProductSpecVariant": { "MetaData": { "DocumentMaterialNumber": "0208057460190c503", "ProductName": "CK", "ProductLongName": "Creatine Kinase", "Language": "en", "DocumentVersion": "2", "DocumentObjectID": "FF00000004D35B0E", "DocumentOriginID": "FF00000004D35A0E", "MaterialNumbers": [ "08057460190" ], "InstrumentReferences": [ { "ID": "9493", "BrandName": "cobas c 303" }, { "ID": "8481", "BrandName": "cobas c 503" } ], "DisclaimerText": "Product information shown on this page contains elements of the officially released Method Sheet. If you require further information please refer to the full Method Sheet PDF under the given link, or contact your local Roche country representative." }, "Chapters": [ { "Name": "IntendedUse", "Value": "

Intended use

In vitro test for the quantitative determination of creatine kinase (CK) in human serum and plasma on Roche/Hitachi cobas c systems.

", "Language": "en" }, { "Name": "TestPrinciple", "Value": "

Test principle

UV‑test

Creatine phosphate + ADP

CK

creatine + ATP

ATP + D‑glucose

HK

ADP + G6P

G6P + NADP+

G6PDH

D‑6‑phosphogluconate + NADPH + H+

Equimolar quantities of NADPH and ATP are formed at the same rate. The photometrically measured rate of formation of NADPH is directly proportional to the CK activity.

", "Language": "en" }, { "Name": "MeasuringRange", "Value": "

Limits and ranges

Measuring range

7‑2000 U/L (0.12‑33.4 µkat/L)

Determine samples having higher activities via the rerun function. Dilution of samples via the rerun function is a 1:11 dilution. Results from samples diluted by the rerun function are automatically multiplied by a factor of 11.

Lower limits of measurement

Limit of Blank, Limit of Detection and Limit of Quantitation

Limit of Blank

= 7 U/L (0.12 µkat/L)

Limit of Detection

= 7 U/L (0.12 µkat/L)

Limit of Quantitation

= 7 U/L (0.12 µkat/L)

The Limit of Blank, Limit of Detection and Limit of Quantitation were determined in accordance with the CLSI (Clinical and Laboratory Standards Institute) EP17‑A2 requirements.

The Limit of Blank is the 95th percentile value from n ≥ 60 measurements of analyte‑free samples over several independent series. The Limit of Blank corresponds to the activity below which analyte‑free samples are found with a probability of 95 %.

The Limit of Detection is determined based on the Limit of Blank and the standard deviation of low activity samples.

The Limit of Detection corresponds to the lowest analyte activity which can be detected (value above the Limit of Blank with a probability of 95 %).

The Limit of Quantitation is the lowest analyte activity that can be reproducibly measured with a total error of 20 %. It has been determined using low activity creatine kinase samples.

", "Language": "en" }, { "Name": "ExpectedValues", "Value": "

Expected values

Reference intervals strongly depend on the patient group and the specific clinical situation.

U/L

For healthy people, according to Klein et al.:
LREFKlein G, Berger A, Bertholf R, et al. Abstract: Multicenter Evaluation of Liquid Reagents for CK, CK-MB and LDH with Determination of Reference Intervals on Hitachi Systems. Clin Chem 2001;47:Suppl. A30.

CK

Men

39‑308 U/L

Women

26‑192 U/L

Consensus values:
LREFThomas L, Müller M, Schumann G, et al. Consensus of DGKL and VDGH for interim reference intervals on enzymes in serum. J Lab Med 2005; 29(5):301-308.

CK

Men

< 190 U/L

Women

< 170 U/L

CK‑MB

Men/women

< 25 U/L

Myocardial infarction: There is a high probability of myocardial damage when the following three conditions are fulfilled:
LREFStein W. Strategie der klinischen-chemischen Diagnostik des frischen Myokardinfarktes. Med Welt 1985;36:572-577.

1

CKmen

> 190 U/L

CKwomen

> 167 U/L

2

CK‑MB

> 24 U/L

3

The CK‑MB activity accounts for 6‑25 % of the total CK‑activity.

According to Tietz:
LREFWu AHB, editor. Tietz Clinical Guide to Laboratory Tests, 4th edition. St. Louis (MO): Saunders Elsevier 2006;306-307.

CK

Adult males > 19 years

20‑200 U/L

Adult females > 19 years

20‑180 U/L

µkat/L

For healthy people, according to Klein et al.:
LREFKlein G, Berger A, Bertholf R, et al. Abstract: Multicenter Evaluation of Liquid Reagents for CK, CK-MB and LDH with Determination of Reference Intervals on Hitachi Systems. Clin Chem 2001;47:Suppl. A30.
*

CK

Men

0.65‑5.14 µkat/L

Women

0.43‑3.21 µkat/L

*calculated by unit conversion factor

Consensus values:
LREFThomas L, Müller M, Schumann G, et al. Consensus of DGKL and VDGH for interim reference intervals on enzymes in serum. J Lab Med 2005; 29(5):301-308.

CK

Men

< 3.20 µkat/L

Women

< 2.85 µkat/L

CK‑MB

Men/women

< 0.42 µkat/L

Myocardial infarction: There is a high probability of myocardial damage when the following three conditions are fulfilled:
LREFStein W. Strategie der klinischen-chemischen Diagnostik des frischen Myokardinfarktes. Med Welt 1985;36:572-577.

1

CKmen

> 3.17 µkat/L

CKwomen

> 2.79 µkat/L

2

CK‑MB

> 0.40 µkat/L

3

The CK‑MB activity accounts for 6‑25 % of the total CK‑activity.

According to Tietz:
LREFWu AHB, editor. Tietz Clinical Guide to Laboratory Tests, 4th edition. St. Louis (MO): Saunders Elsevier 2006;306-307.
*

CK

Adult males > 19 years

0.33‑3.34 µkat/L

Adult females > 19 years

0.33‑3.01 µkat/L

*calculated by unit conversion factor

The reference values according to Klein et al. are based on the 95th percentile of a group of healthy persons (202 men and 217 women) not involved in high‑intensity athletic activities.

In order to ensure high sensitivity in the diagnosis of heart diseases the values given by Tietz are recommended. The loss of diagnostic specificity thereby incurred can be compensated for by additionally determining CK‑MB and/or troponin T. When myocardial infarction is suspected the diagnostic strategy proposals in the consensus document of European and American cardiologists should in general be followed.

LREFMyocardial Infarction Redefined - A Consensus Document of the Joint European Society of Cardiology/ American College of Cardiology Committee for the Redefinition of Myocardial Infarction. Eur Heart J 2000;21:1502-1513.

If despite the suspicion of myocardial infarction the values found remain below the stated limits, a fresh infarction may be involved. In such cases, the determinations should be repeated after 4 hours.

CK varies with physical activity level and race in healthy individuals.

LREFWu AHB, editor. Tietz Clinical Guide to Laboratory Tests, 4th edition. St. Louis (MO): Saunders Elsevier 2006;306-307.
,
LREFBlack HR, Quallich H, Gareleck CB. Racial differences in serum creatine kinase levels. Am J Med 1986;81:479-487.

Each laboratory should investigate the transferability of the expected values to its own patient population and if necessary determine its own reference ranges.

", "Language": "en" }, { "Name": "LimitationInterference", "Value": "

Limitations - interference

Criterion: Recovery within ± 10 % of initial value at a creatine kinase activity of 140 U/L.

Icterus:

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an I index of 60 for conjugated and unconjugated bilirubin (approximate conjugated and unconjugated bilirubin concentration: 1026 µmol/L or 60 mg/dL).

Hemolysis:

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an H index of 100 (approximate hemoglobin concentration: 62.1 µmol/L or 100 mg/dL). The level of interference may be variable depending on the exact content of erythrocytes.

Lipemia (Intralipid):

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an L index of 1000. There is poor correlation between the L index (corresponds to turbidity) and triglycerides concentration. Highly lipemic specimens (L index > 1000) may cause high absorbance flagging. Choose diluted sample treatment for automatic rerun.

Drugs: No interference was found at therapeutic concentrations using common drug panels.

LREFBreuer J. Report on the Symposium "Drug effects in Clinical Chemistry Methods". Eur J Clin Chem Clin Biochem 1996;34:385-386.
,
LREFSonntag O, Scholer A. Drug interference in clinical chemistry: recommendation of drugs and their concentrations to be used in drug interference studies. Ann Clin Biochem 2001;38:376-385.
Exception: Cyanokit (hydroxocobalamin) at therapeutic concentrations interferes with the test.

In very rare cases, gammopathy, in particular type IgM (Waldenström’s macroglobulinemia), may cause unreliable results.

LREFBakker AJ, Mücke M. Gammopathy interference in clinical chemistry assays: mechanisms, detection and prevention. Clin Chem Lab Med 2007;45(9):1240-1243.

For diagnostic purposes, the results should always be assessed in conjunction with the patient’s medical history, clinical examination and other findings.

ACTION REQUIRED
Special Wash Programming: The use of special wash steps is mandatory when certain test combinations are run together on cobas c systems. All special wash programming necessary for avoiding carry-over is available via the cobas link. The latest version of the carry-over evasion list can be found with the NaOHD/SMS/SCCS Method Sheet. For further instructions, refer to the operator’s manual.

", "Language": "en" }, { "Name": "OrderInformation", "Value": "

OrderInformation (CC Reagents - cobas + Integra)

Order information

Analyzer(s) on which cobas c pack(s) can be used

08057460190

Creatine Kinase (500 tests)

System-ID 2042 001

cobas c 303, cobas c 503

10759350360

Calibrator f.a.s. (12 x 3 mL)

Code 20401

05947626160

PreciControl ClinChem Multi 1 (4 x 5 mL)

Code 20391

05947774160

PreciControl ClinChem Multi 2 (4 x 5 mL)

Code 20392

08063494190

Diluent NaCl 9 % (123 mL)

System-ID 2906 001

", "Language": "en" }, { "Name": "SystemInformation", "Value": "

System information

CK2: ACN 20420

", "Language": "en" }, { "Name": "Handling", "Value": "

Reagent handling

Ready for use

", "Language": "en" }, { "Name": "TestDefinition", "Value": "

Application for serum and plasma

Test definition

Reporting time

10 min

Wavelength (sub/main)

546/340 nm

Reagent pipetting

Diluent (H2O)

R1

79 µL

R3

16 µL

Sample volumes

Sample

Sample dilution

Sample

Diluent (NaCl)

Normal

2.2 µL

Decreased

2.2 µL

10 µL

100 µL

Increased

2.2 µL

For further information about the assay test definitions refer to the application parameters setting screen of the corresponding analyzer and assay.

", "Language": "en" }, { "Name": "StorageStability", "Value": "

Storage and stability

Shelf life at 2‑8 °C:

See expiration date on cobas c pack label.

On‑board in use and refrigerated on the analyzer:

8 weeks

", "Language": "en" }, { "Name": "Calibration", "Value": "

Calibration

Calibrators

S1: H2O

S2: C.f.a.s.

Calibration mode

Linear

Calibration frequency

Automatic full calibration
- after reagent lot change

Full calibration
- as required following quality control procedures

Calibration interval may be extended based on acceptable verification of calibration by the laboratory.

Traceability: This method has been standardized against the IFCC Method for Creatine Kinase.

LREFSchumann G, Bonora R, Ceriotti F, et al. IFCC Primary Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes at 37 °C – Part 2. Reference Procedure for the Measurement of Catalytic Concentration of Creatine Kinase. Clin Chem Lab Med 2002;40(6):635-642.

", "Language": "en" }, { "Name": "Limitations", "Value": "", "Language": "en" }, { "Name": "PerformanceData", "Value": "

Specific performance data

Representative performance data on the analyzers are given below. These data represent the performance of the analytical procedure itself.

Results obtained in individual laboratories may differ due to heterogenous sample materials, aging of analyzer components and mixture of reagents running on the analyzer.

", "Language": "en" }, { "Name": "Precision", "Value": "

Precision

Precision was determined using human samples and controls in accordance with the CLSI (Clinical and Laboratory Standards Institute) EP05‑A3 requirements with repeatability (n = 84) and intermediate precision (2 aliquots per run, 2 runs per day, 21 days). Results for repeatability and intermediate precision were obtained on the cobas c 503 analyzer.

Repeatability

Mean
U/L

SD
U/L

CV
%

PCCC1a)

155

0.764

0.5

PCCC2b)

287

0.988

0.3

Human serum 1

19.5

0.524

2.7

Human serum 2

85.7

0.510

0.6

Human serum 3

176

1.12

0.6

Human serum 4

900

3.28

0.4

Human serum 5

1588

4.52

0.3

Intermediate precision

Mean
U/L

SD
U/L

CV
%

PCCC1

FREFPreciControl ClinChem Multi 1

155

1.04

0.7

PCCC2

FREFPreciControl ClinChem Multi 2

287

2.02

0.7

Human serum 1

19.4

0.582

3.0

Human serum 2

85.7

1.01

1.2

Human serum 3

176

1.96

1.1

Human serum 4

895

10.7

1.2

Human serum 5

1588

18.7

1.2

", "Language": "en" }, { "Name": "MethodComparison", "Value": "

Method comparison

Creatine kinase values for human serum and plasma samples obtained on a cobas c 503 analyzer (y) were compared with those determined using the corresponding reagent on a cobas c 501 analyzer (x).

Sample size (n) = 80

Passing/Bablok

LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790.

Linear regression

y = 0.988x + 1.20 U/L

y = 0.993x − 0.788 U/L

τ = 0.996

r = 1.000

The sample activities were between 8.20 and 1938 U/L.

Creatine kinase values for human serum and plasma samples obtained on a cobas c 303 analyzer (y) were compared with those determined using the corresponding reagent on a cobas c 501 analyzer (x).

Sample size (n) = 110

Passing/Bablok

LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790.

Linear regression

y = 1.006x + 0.553 U/L

y = 1.013x − 1.03 U/L

τ = 0.990

r = 1.000

The sample activites were between 11.0 and 1959 U/L.

", "Language": "en" }, { "Name": "Summary", "Value": "

Summary

Creatine kinase (CK) is a dimeric enzyme occurring in four different forms: a mitochondrial isoenzyme and the cytosolic isoenzymes CK‑MM (skeletal muscle type), CK‑BB (brain type) and CK‑MB (myocardial type).

LREFThomas L, ed. Labor und Diagnose, 8th ed. Bd 1:TH-Books Verlagsgesellschaft 2012.

The determination of CK and CK‑isoenzyme activities is utilized in the diagnosis and monitoring of myocardial infarction and myopathies such as the progressive Duchenne muscular dystrophy. Following injury to the myocardium, such as occurs with acute myocardial infarction

LREFThomas L, ed. Labor und Diagnose, 8th ed. Bd 1:TH-Books Verlagsgesellschaft 2012.
, CK is released from the damaged myocardial cells. In early cases, a rise in the CK‑activity can be found just 4 hours after an infarction.
LREFThomas L, ed. Labor und Diagnose, 8th ed. Bd 1:TH-Books Verlagsgesellschaft 2012.
,
LREFStein W. Laboratory Diagnosis of Acute Myocardial Infarction. Darmstadt: GIT Verlag 1988;34-37.
The CK activity reaches a maximum after 12‑24 hours and then falls back to the normal range after 3‑4 days.
LREFThomas L, ed. Labor und Diagnose, 8th ed. Bd 1:TH-Books Verlagsgesellschaft 2012.
,
LREFStein W. Laboratory Diagnosis of Acute Myocardial Infarction. Darmstadt: GIT Verlag 1988;34-37.

The assay method using creatine phosphate and ADP was first described by Oliver

LREFOliver IT. A spectrophotometric method for the determination of creatine phosphokinase and myokinase. Biochem J 1955;61:116-122.
, modified by Rosalki
LREFRosalki SB. An improved procedure for serum creatine phosphokinase determination. J Lab Clin Med 1967;69:696-705.
and further improved for optimal test conditions by Szasz et al.
LREFSzasz G, Gruber W, Bernt E. Creatine kinase in serum: 1. Determination of optimum reaction conditions. Clin Chem 1976;22(5):650-656.
CK is rapidly inactivated by oxidation of the sulfhydryl groups in the active center. The enzyme can be reactivated by the addition of acetylcysteine (NAC).
LREFSzasz G, Gruber W, Bernt E. Creatine kinase in serum: 1. Determination of optimum reaction conditions. Clin Chem 1976;22(5):650-656.
Interference by adenylate kinase is prevented by the addition of diadenosine pentaphosphate
LREFStandard method for the determination of creatine kinase activity. J Clin Chem Clin Biochem 1977;15:249-260.
and AMP.
LREFSzasz G, Gruber W, Bernt E. Creatine kinase in serum: 1. Determination of optimum reaction conditions. Clin Chem 1976;22(5):650-656.
,
LREFStandard method for the determination of creatine kinase activity. J Clin Chem Clin Biochem 1977;15:249-260.

Standardized methods for the determination of CK with activation by NAC were recommended by the German Society for Clinical Chemistry (DGKC)

LREFStandard method for the determination of creatine kinase activity. J Clin Chem Clin Biochem 1977;15:249-260.
in 1977 and the International Federation of Clinical Chemistry (IFCC)
LREFHørder M, Elser RC, Gerhardt M, et al. Approved Recommendation on IFCC Methods for the Measurement of Catalytic Concentration of Enzymes. Part 7. IFCC Method for Creatine Kinase. Eur J Clin Chem Clin Biochem 1991;29:435-456.
in 1991. In 2002 the IFCC confirmed their recommendation and extended it to 37 °C.
LREFSchumann G, Bonora R, Ceriotti F, et al. IFCC Primary Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes at 37 °C – Part 2. Reference Procedure for the Measurement of Catalytic Concentration of Creatine Kinase. Clin Chem Lab Med 2002;40(6):635-642.
,
LREFKlauke R, Schmidt E, Lorentz K. Recommendations for carrying out standard ECCLS procedures (1988) for the catalytic concentrations of creatine kinase, aspartate aminotransferase, alanine aminotransferase and γ-glutamyltransferase at 37 °C. Eur J Clin Chem Clin Biochem 1993;31:901-909.
The method described here is derived from the formulation recommended by the IFCC and was optimized for performance and stability.

", "Language": "en" }, { "Name": "Reagents", "Value": "

Reagents - working solutions

R1

Imidazole buffer: 123 mmol/L, pH 6.5 (37 °C); EDTA: 2.46 mmol/L; Mg2+: 12.3 mmol/L; ADP: 2.46 mmol/L; AMP: 6.14 mmol/L; diadenosine pentaphosphate: 19 µmol/L; NADP+ (yeast): 2.46 mmol/L; N‑acetylcysteine: 24.6 mmol/L; HK (yeast): ≥ 36.7 µkat/L; G6PDH (E. coli): ≥ 23.4 µkat/L; preservative; stabilizers; additives.

R3

CAPSO* buffer: 20 mmol/L, pH 8.8 (37 °C); glucose: 120 mmol/L; EDTA: 2.46 mmol/L; creatine phosphate: 184 mmol/L; preservative; stabilizers.

*CAPSO: 3‑(cyclohexylamine)‑2‑hydroxy‑1‑propanesulfonic acid

R1 is in position B and R3 is in position C.

", "Language": "en" }, { "Name": "PrecautionsWarnings", "Value": "

Precautions and warnings

For in vitro diagnostic use.
Exercise the normal precautions required for handling all laboratory reagents.
Disposal of all waste material should be in accordance with local guidelines.
Safety data sheet available for professional user on request.

This kit contains components classified as follows in accordance with the Regulation (EC) No. 1272/2008:

For USA: Caution: Federal law restricts this device to sale by or on the order of a physician.

Danger

H360D

May damage the unborn child.

Prevention:

P201

Obtain special instructions before use.

P202

Do not handle until all safety precautions have been read and understood.

P280

Wear protective gloves/ protective clothing/ eye protection/ face protection/ hearing protection.

Response:

P308 + P313

IF exposed or concerned: Get medical advice/attention.

Storage:

P405

Store locked up.

Disposal:

P501

Dispose of contents/container to an approved waste disposal plant.

Product safety labeling follows EU GHS guidance.

Contact phone: 1-800-428-2336

", "Language": "en" }, { "Name": "Caution", "Value": "", "Language": "en" }, { "Name": "QualityControl", "Value": "

Quality control

For quality control, use control materials as listed in the \"Order information\" section.

In addition, other suitable control material can be used.

The control intervals and limits should be adapted to each laboratory’s individual requirements. It is recommended to perform quality control always after lot calibration and subsequently at least every 8 weeks. Values obtained should fall within the defined limits. Each laboratory should establish corrective measures to be taken if values fall outside the defined limits.

Follow the applicable government regulations and local guidelines for quality control.

", "Language": "en" }, { "Name": "SpecimenPreparation", "Value": "

Specimen collection and preparation

For specimen collection and preparation only use suitable tubes or collection containers.

Only the specimens listed below were tested and found acceptable.
Serum: Nonhemolyzed serum is the specimen of choice and also recommended by IFCC.
Plasma: Li‑heparin, K2‑, K3‑EDTA plasma.

Please note: Differences in the degree of hemolysis resulting from the blood sampling procedure used can lead to deviating results in serum and plasma.

The sample types listed were tested with a selection of sample collection tubes that were commercially available at the time of testing, i.e. not all available tubes of all manufacturers were tested. Sample collection systems from various manufacturers may contain differing materials which could affect the test results in some cases. When processing samples in primary tubes (sample collection systems), follow the instructions of the tube manufacturer.

Centrifuge samples containing precipitates before performing the assay.

See the limitations and interferences section for details about possible sample interferences.

Stability in serum:

LREFGuder WG, Narayanan S, Wisser H, et al. List of Analytes; Preanalytical Variables. Brochure in: Samples: From the Patient to the Laboratory. Darmstadt: GIT-Verlag 1996.

2 days at 20‑25 °C

7 days at 4‑8 °C

4 weeks at -20 °C

Stability in EDTA/heparin plasma:

2 days at 15‑25 °C

7 days at 2‑8 °C

4 weeks at (-15)‑(-25) °C

Sample stability claims were established by experimental data by the manufacturer or based on reference literature and only for the temperatures/time frames as stated in the method sheet. It is the responsibility of the individual laboratory to use all available references and/or its own studies to determine specific stability criteria for its laboratory.

", "Language": "en" } ] } }, { "ProductSpecVariant": { "MetaData": { "DocumentMaterialNumber": "0108057460190c503", "ProductName": "CK", "ProductLongName": "Creatine Kinase", "Language": "en", "DocumentVersion": "5", "DocumentObjectID": "FF0000000595DE0E", "DocumentOriginID": "FF000000045FE20E", "MaterialNumbers": [ "08057460190" ], "InstrumentReferences": [ { "ID": "9493", "BrandName": "cobas c 303" }, { "ID": "8481", "BrandName": "cobas c 503" } ], "DisclaimerText": "Product information shown on this page contains elements of the officially released Method Sheet. If you require further information please refer to the full Method Sheet PDF under the given link, or contact your local Roche country representative." }, "Chapters": [ { "Name": "IntendedUse", "Value": "

Intended use

In vitro test for the quantitative determination of creatine kinase (CK) in human serum and plasma on cobas c systems.

", "Language": "en" }, { "Name": "TestPrinciple", "Value": "

Test principle

UV‑test

Creatine phosphate + ADP

CK

creatine + ATP

ATP + D‑glucose

HK

ADP + G6P

G6P + NADP+

G6PDH

D‑6‑phosphogluconate + NADPH + H+

Equimolar quantities of NADPH and ATP are formed at the same rate. The photometrically measured rate of formation of NADPH is directly proportional to the CK activity.

", "Language": "en" }, { "Name": "MeasuringRange", "Value": "

Limits and ranges

Measuring range

7‑2000 U/L (0.12‑33.4 µkat/L)

Determine samples having higher activities via the rerun function. Dilution of samples via the rerun function is a 1:11 dilution. Results from samples diluted by the rerun function are automatically multiplied by a factor of 11.

Lower limits of measurement

Limit of Blank, Limit of Detection and Limit of Quantitation

Limit of Blank

= 7 U/L (0.12 µkat/L)

Limit of Detection

= 7 U/L (0.12 µkat/L)

Limit of Quantitation

= 7 U/L (0.12 µkat/L)

The Limit of Blank, Limit of Detection and Limit of Quantitation were determined in accordance with the CLSI (Clinical and Laboratory Standards Institute) EP17‑A2 requirements.

The Limit of Blank is the 95th percentile value from n ≥ 60 measurements of analyte‑free samples over several independent series. The Limit of Blank corresponds to the activity below which analyte‑free samples are found with a probability of 95 %.

The Limit of Detection is determined based on the Limit of Blank and the standard deviation of low activity samples.

The Limit of Detection corresponds to the lowest analyte activity which can be detected (value above the Limit of Blank with a probability of 95 %).

The Limit of Quantitation is the lowest analyte activity that can be reproducibly measured with a total error of 20 %. It has been determined using low activity creatine kinase samples.

", "Language": "en" }, { "Name": "ExpectedValues", "Value": "

Expected values

Reference intervals strongly depend on the patient group and the specific clinical situation.

U/L

For healthy people, according to Klein et al.:
LREFKlein G, Berger A, Bertholf R, et al. Abstract: Multicenter Evaluation of Liquid Reagents for CK, CK-MB and LDH with Determination of Reference Intervals on Hitachi Systems. Clin Chem 2001;47:Suppl. A30.

CK

Men

39‑308 U/L

Women

26‑192 U/L

Consensus values:
LREFThomas L, Müller M, Schumann G, et al. Consensus of DGKL and VDGH for interim reference intervals on enzymes in serum. J Lab Med 2005; 29(5):301-308.

CK

Men

< 190 U/L

Women

< 170 U/L

CK‑MB

Men/women

< 25 U/L

Myocardial infarction: There is a high probability of myocardial damage when the following three conditions are fulfilled:
LREFStein W. Strategie der klinischen-chemischen Diagnostik des frischen Myokardinfarktes. Med Welt 1985;36:572-577.

1

CKmen

> 190 U/L

CKwomen

> 167 U/L

2

CK‑MB

> 24 U/L

3

The CK‑MB activity accounts for 6‑25 % of the total CK‑activity.

According to Tietz:
LREFWu AHB, editor. Tietz Clinical Guide to Laboratory Tests, 4th edition. St. Louis (MO): Saunders Elsevier 2006;306-307.

CK

Adult males > 19 years

20‑200 U/L

Adult females > 19 years

20‑180 U/L

µkat/L

For healthy people, according to Klein et al.:
LREFKlein G, Berger A, Bertholf R, et al. Abstract: Multicenter Evaluation of Liquid Reagents for CK, CK-MB and LDH with Determination of Reference Intervals on Hitachi Systems. Clin Chem 2001;47:Suppl. A30.
*

CK

Men

0.65‑5.14 µkat/L

Women

0.43‑3.21 µkat/L

*calculated by unit conversion factor

Consensus values:
LREFThomas L, Müller M, Schumann G, et al. Consensus of DGKL and VDGH for interim reference intervals on enzymes in serum. J Lab Med 2005; 29(5):301-308.

CK

Men

< 3.20 µkat/L

Women

< 2.85 µkat/L

CK‑MB

Men/women

< 0.42 µkat/L

Myocardial infarction: There is a high probability of myocardial damage when the following three conditions are fulfilled:
LREFStein W. Strategie der klinischen-chemischen Diagnostik des frischen Myokardinfarktes. Med Welt 1985;36:572-577.

1

CKmen

> 3.17 µkat/L

CKwomen

> 2.79 µkat/L

2

CK‑MB

> 0.40 µkat/L

3

The CK‑MB activity accounts for 6‑25 % of the total CK‑activity.

According to Tietz:
LREFWu AHB, editor. Tietz Clinical Guide to Laboratory Tests, 4th edition. St. Louis (MO): Saunders Elsevier 2006;306-307.
*

CK

Adult males > 19 years

0.33‑3.34 µkat/L

Adult females > 19 years

0.33‑3.01 µkat/L

*calculated by unit conversion factor

The reference values according to Klein et al. are based on the 95th percentile of a group of healthy persons (202 men and 217 women) not involved in high‑intensity athletic activities.

In order to ensure high sensitivity in the diagnosis of heart diseases the values given by Tietz are recommended. The loss of diagnostic specificity thereby incurred can be compensated for by additionally determining CK‑MB and/or troponin T. When myocardial infarction is suspected the diagnostic strategy proposals in the consensus document of European and American cardiologists should in general be followed.

LREFMyocardial Infarction Redefined - A Consensus Document of the Joint European Society of Cardiology/ American College of Cardiology Committee for the Redefinition of Myocardial Infarction. Eur Heart J 2000;21:1502-1513.

If despite the suspicion of myocardial infarction the values found remain below the stated limits, a fresh infarction may be involved. In such cases, the determinations should be repeated after 4 hours.

CK varies with physical activity level and race in healthy individuals.

LREFWu AHB, editor. Tietz Clinical Guide to Laboratory Tests, 4th edition. St. Louis (MO): Saunders Elsevier 2006;306-307.
,
LREFBlack HR, Quallich H, Gareleck CB. Racial differences in serum creatine kinase levels. Am J Med 1986;81:479-487.

Each laboratory should investigate the transferability of the expected values to its own patient population and if necessary determine its own reference ranges.

", "Language": "en" }, { "Name": "LimitationInterference", "Value": "

Limitations - interference

Criterion: Recovery within ± 10 % of initial value at a creatine kinase activity of 140 U/L.

Icterus:

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an I index of 60 for conjugated and unconjugated bilirubin (approximate conjugated and unconjugated bilirubin concentration: 1026 µmol/L or 60 mg/dL).

Hemolysis:

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an H index of 100 (approximate hemoglobin concentration: 62.1 µmol/L or 100 mg/dL). The level of interference may be variable depending on the exact content of erythrocytes.

Lipemia (Intralipid):

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an L index of 1000. There is poor correlation between the L index (corresponds to turbidity) and triglycerides concentration. Highly lipemic specimens (L index > 1000) may cause high absorbance flagging.

Drugs: No interference was found at therapeutic concentrations using common drug panels.

LREFBreuer J. Report on the Symposium "Drug effects in Clinical Chemistry Methods". Eur J Clin Chem Clin Biochem 1996;34:385-386.
,
LREFSonntag O, Scholer A. Drug interference in clinical chemistry: recommendation of drugs and their concentrations to be used in drug interference studies. Ann Clin Biochem 2001;38:376-385.
Exception: Cyanokit (hydroxocobalamin) at therapeutic concentrations interferes with the test.

In very rare cases, gammopathy, in particular type IgM (Waldenström’s macroglobulinemia), may cause unreliable results.

LREFBakker AJ, Mücke M. Gammopathy interference in clinical chemistry assays: mechanisms, detection and prevention. Clin Chem Lab Med 2007;45(9):1240-1243.

For diagnostic purposes, the results should always be assessed in conjunction with the patient’s medical history, clinical examination and other findings.

ACTION REQUIRED
Special Wash Programming: The use of special wash steps is mandatory when certain test combinations are run together on cobas c systems. All special wash programming necessary for avoiding carry-over is available via the cobas link. The latest version of the carry-over evasion list can be found with the NaOHD/SMS/SCCS Method Sheet for information. For further instructions refer to the operator’s manual.

", "Language": "en" }, { "Name": "OrderInformation", "Value": "

OrderInformation (CC Reagents - cobas + Integra)

Order information

Analyzer(s) on which cobas c pack(s) can be used

08057460190

Creatine Kinase (500 tests)

System-ID 2042 001

cobas c 303, cobas c 503

Materials required (but not provided):

10759350190

Calibrator f.a.s. (12 x 3 mL)

Code 20401

05117003190

PreciControl ClinChem Multi 1 (20 x 5 mL)

Code 20391

05947626190

PreciControl ClinChem Multi 1 (4 x 5 mL)

Code 20391

05117216190

PreciControl ClinChem Multi 2 (20 x 5 mL)

Code 20392

05947774190

PreciControl ClinChem Multi 2 (4 x 5 mL)

Code 20392

08063494190

Diluent NaCl 9 % (123 mL)

System-ID 2906 001

", "Language": "en" }, { "Name": "SystemInformation", "Value": "

System information

CK2: ACN 20420

", "Language": "en" }, { "Name": "Handling", "Value": "

Reagent handling

Ready for use

", "Language": "en" }, { "Name": "TestDefinition", "Value": "

Application for serum and plasma

Test definition

Reporting time

10 min

Wavelength (sub/main)

546/340 nm

Reagent pipetting

Diluent (H2O)

R1

79 µL

R3

16 µL

Sample volumes

Sample

Sample dilution

Sample

Diluent (NaCl)

Normal

2.2 µL

Decreased

2.2 µL

10 µL

100 µL

Increased

2.2 µL

For further information about the assay test definitions refer to the application parameters setting screen of the corresponding analyzer and assay.

", "Language": "en" }, { "Name": "StorageStability", "Value": "

Storage and stability

Shelf life at 2‑8 °C:

See expiration date on cobas c pack label.

On‑board in use and refrigerated on the analyzer:

8 weeks

", "Language": "en" }, { "Name": "Calibration", "Value": "

Calibration

Calibrators

S1: H2O

S2: C.f.a.s.

Calibration mode

Linear

Calibration frequency

Automatic full calibration
- after reagent lot change

Full calibration
- as required following quality control procedures

Calibration interval may be extended based on acceptable verification of calibration by the laboratory.

Traceability: This method has been standardized against the IFCC Method for Creatine Kinase.

LREFSchumann G, Bonora R, Ceriotti F, et al. IFCC Primary Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes at 37 °C – Part 2. Reference Procedure for the Measurement of Catalytic Concentration of Creatine Kinase. Clin Chem Lab Med 2002;40(6):635-642.

", "Language": "en" }, { "Name": "Limitations", "Value": "", "Language": "en" }, { "Name": "PerformanceData", "Value": "

Specific performance data

Representative performance data on the analyzers are given below. These data represent the performance of the analytical procedure itself.

Results obtained in individual laboratories may differ due to heterogenous sample materials, aging of analyzer components and mixture of reagents running on the analyzer.

", "Language": "en" }, { "Name": "Precision", "Value": "

Precision

Precision was determined using human samples and controls in accordance with the CLSI (Clinical and Laboratory Standards Institute) EP05-A3 requirements with repeatability (n = 84) and intermediate precision (2 aliquots per run, 2 runs per day, 21 days). Results for repeatability and intermediate precision were obtained on the cobas c 503 analyzer.

Repeatability

Mean
U/L

SD
U/L

CV
%

PCCC1a)

155

0.764

0.5

PCCC2b)

287

0.988

0.3

Human serum 1

19.5

0.524

2.7

Human serum 2

85.7

0.510

0.6

Human serum 3

176

1.12

0.6

Human serum 4

900

3.28

0.4

Human serum 5

1588

4.52

0.3

Intermediate precision

Mean
U/L

SD
U/L

CV
%

PCCC1

FREFPreciControl ClinChem Multi 1

155

1.04

0.7

PCCC2

FREFPreciControl ClinChem Multi 2

287

2.02

0.7

Human serum 1

19.4

0.582

3.0

Human serum 2

85.7

1.01

1.2

Human serum 3

176

1.96

1.1

Human serum 4

895

10.7

1.2

Human serum 5

1588

18.7

1.2

The data obtained on cobas c 503 analyzer(s) are representative for cobas c 303 analyzer(s).

", "Language": "en" }, { "Name": "MethodComparison", "Value": "

Method comparison

Creatine kinase values for human serum and plasma samples obtained on a cobas c 503 analyzer (y) were compared with those determined using the corresponding reagent on a cobas c 501 analyzer (x).

Sample size (n) = 80

Passing/Bablok

LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790.

Linear regression

y = 0.988x + 1.20 U/L

y = 0.993x − 0.788 U/L

τ = 0.996

r = 1.000

The sample activities were between 8.20 and 1938 U/L.

Creatine kinase values for human serum and plasma samples obtained on a cobas c 303 analyzer (y) were compared with those determined using the corresponding reagent on a cobas c 501 analyzer (x).

Sample size (n) = 110

Passing/Bablok

LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790.

Linear regression

y = 1.006x + 0.553 U/L

y = 1.013x − 1.03 U/L

τ = 0.990

r = 1.000

The sample activities were between 11.0 and 1959 U/L.

", "Language": "en" }, { "Name": "Summary", "Value": "

Summary

Creatine kinase (CK) is a dimeric enzyme occurring in four different forms: a mitochondrial isoenzyme and the cytosolic isoenzymes CK‑MM (skeletal muscle type), CK‑BB (brain type) and CK‑MB (myocardial type).

LREFThomas L, ed. Labor und Diagnose, 8th ed. Bd 1:TH-Books Verlagsgesellschaft 2012.

The determination of CK and CK‑isoenzyme activities is utilized in the diagnosis and monitoring of myocardial infarction and myopathies such as the progressive Duchenne muscular dystrophy. Following injury to the myocardium, such as occurs with acute myocardial infarction

LREFThomas L, ed. Labor und Diagnose, 8th ed. Bd 1:TH-Books Verlagsgesellschaft 2012.
, CK is released from the damaged myocardial cells. In early cases, a rise in the CK‑activity can be found just 4 hours after an infarction.
LREFThomas L, ed. Labor und Diagnose, 8th ed. Bd 1:TH-Books Verlagsgesellschaft 2012.
,
LREFStein W. Laboratory Diagnosis of Acute Myocardial Infarction. Darmstadt: GIT Verlag 1988;34-37.
The CK activity reaches a maximum after 12‑24 hours and then falls back to the normal range after 3‑4 days.
LREFThomas L, ed. Labor und Diagnose, 8th ed. Bd 1:TH-Books Verlagsgesellschaft 2012.
,
LREFStein W. Laboratory Diagnosis of Acute Myocardial Infarction. Darmstadt: GIT Verlag 1988;34-37.

The assay method using creatine phosphate and ADP was first described by Oliver

LREFOliver IT. A spectrophotometric method for the determination of creatine phosphokinase and myokinase. Biochem J 1955;61:116-122.
, modified by Rosalki
LREFRosalki SB. An improved procedure for serum creatine phosphokinase determination. J Lab Clin Med 1967;69:696-705.
and further improved for optimal test conditions by Szasz et al.
LREFSzasz G, Gruber W, Bernt E. Creatine kinase in serum: 1. Determination of optimum reaction conditions. Clin Chem 1976;22(5):650-656.
CK is rapidly inactivated by oxidation of the sulfhydryl groups in the active center. The enzyme can be reactivated by the addition of acetylcysteine (NAC).
LREFSzasz G, Gruber W, Bernt E. Creatine kinase in serum: 1. Determination of optimum reaction conditions. Clin Chem 1976;22(5):650-656.
Interference by adenylate kinase is prevented by the addition of diadenosine pentaphosphate
LREFStandard method for the determination of creatine kinase activity. J Clin Chem Clin Biochem 1977;15:249-260.
and AMP.
LREFSzasz G, Gruber W, Bernt E. Creatine kinase in serum: 1. Determination of optimum reaction conditions. Clin Chem 1976;22(5):650-656.
,
LREFStandard method for the determination of creatine kinase activity. J Clin Chem Clin Biochem 1977;15:249-260.

Standardized methods for the determination of CK with activation by NAC were recommended by the German Society for Clinical Chemistry (DGKC)

LREFStandard method for the determination of creatine kinase activity. J Clin Chem Clin Biochem 1977;15:249-260.
in 1977 and the International Federation of Clinical Chemistry (IFCC)
LREFHørder M, Elser RC, Gerhardt M, et al. Approved Recommendation on IFCC Methods for the Measurement of Catalytic Concentration of Enzymes. Part 7. IFCC Method for Creatine Kinase. Eur J Clin Chem Clin Biochem 1991;29:435-456.
in 1991. In 2002 the IFCC confirmed their recommendation and extended it to 37 °C.
LREFSchumann G, Bonora R, Ceriotti F, et al. IFCC Primary Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes at 37 °C – Part 2. Reference Procedure for the Measurement of Catalytic Concentration of Creatine Kinase. Clin Chem Lab Med 2002;40(6):635-642.
,
LREFKlauke R, Schmidt E, Lorentz K. Recommendations for carrying out standard ECCLS procedures (1988) for the catalytic concentrations of creatine kinase, aspartate aminotransferase, alanine aminotransferase and γ-glutamyltransferase at 37 °C. Eur J Clin Chem Clin Biochem 1993;31:901-909.
The method described here is derived from the formulation recommended by the IFCC and was optimized for performance and stability.

", "Language": "en" }, { "Name": "Reagents", "Value": "

Reagents - working solutions

R1

Imidazole buffer: 123 mmol/L, pH 6.5 (37 °C); EDTA: 2.46 mmol/L; Mg2+: 12.3 mmol/L; ADP: 2.46 mmol/L; AMP: 6.14 mmol/L; diadenosine pentaphosphate: 19 µmol/L; NADP+ (yeast): 2.46 mmol/L; N‑acetylcysteine: 24.6 mmol/L; HK (yeast): ≥ 36.7 µkat/L; G6PDH (E. coli): ≥ 23.4 µkat/L; preservative; stabilizers; additives.

R3

CAPSO* buffer: 20 mmol/L, pH 8.8 (37 °C); glucose: 120 mmol/L; EDTA: 2.46 mmol/L; creatine phosphate: 184 mmol/L; preservative; stabilizers.

*CAPSO: 3‑(cyclohexylamine)‑2‑hydroxy‑1‑propanesulfonic acid

R1 is in position B and R3 is in position C.

", "Language": "en" }, { "Name": "PrecautionsWarnings", "Value": "

Precautions and warnings

For in vitro diagnostic use for health care professionals. Exercise the normal precautions required for handling all laboratory reagents.

Infectious or microbial waste:
Warning: handle waste as potentially biohazardous material. Dispose of waste according to accepted laboratory instructions and procedures.

Environmental hazards:
Apply all relevant local disposal regulations to determine the safe disposal.

Safety data sheet available for professional user on request.

This kit contains components classified as follows in accordance with the Regulation (EC) No. 1272/2008:

Danger

H360D

May damage the unborn child.

Prevention:

P201

Obtain special instructions before use.

P202

Do not handle until all safety precautions have been read and understood.

P280

Wear protective gloves/ protective clothing/ eye protection/ face protection/ hearing protection.

Response:

P308 + P313

IF exposed or concerned: Get medical advice/attention.

Storage:

P405

Store locked up.

Disposal:

P501

Dispose of contents/container to an approved waste disposal plant.

Product safety labeling follows EU GHS guidance.

Contact phone: all countries: +49-621-7590

", "Language": "en" }, { "Name": "Caution", "Value": "", "Language": "en" }, { "Name": "QualityControl", "Value": "

Quality control

For quality control, use control materials as listed in the “Order information” section. In addition, other suitable control material can be used.

The control intervals and limits should be adapted to each laboratory’s individual requirements. It is recommended to perform quality control always after lot calibration and subsequently at least every 8 weeks. Values obtained should fall within the defined limits. Each laboratory should establish corrective measures to be taken if values fall outside the defined limits.

Follow the applicable government regulations and local guidelines for quality control.

", "Language": "en" }, { "Name": "SpecimenPreparation", "Value": "

Specimen collection and preparation

For specimen collection and preparation only use suitable tubes or collection containers.

Only the specimens listed below were tested and found acceptable.
Serum: Nonhemolyzed serum is the specimen of choice and also recommended by IFCC.
Plasma: Li‑heparin, K2‑, K3‑EDTA plasma.

Please note: Differences in the degree of hemolysis resulting from the blood sampling procedure used can lead to deviating results in serum and plasma.

The sample types listed were tested with a selection of sample collection tubes that were commercially available at the time of testing, i.e. not all available tubes of all manufacturers were tested. Sample collection systems from various manufacturers may contain differing materials which could affect the test results in some cases. When processing samples in primary tubes (sample collection systems), follow the instructions of the tube manufacturer.

Centrifuge samples containing precipitates before performing the assay.

See the limitations and interferences section for details about possible sample interferences.

Stability in serum:

LREFGuder WG, Narayanan S, Wisser H, et al. List of Analytes; Preanalytical Variables. Brochure in: Samples: From the Patient to the Laboratory. Darmstadt: GIT-Verlag 1996.

2 days at 20‑25 °C

7 days at 4‑8 °C

4 weeks at -20 °C

Stability in EDTA/heparin plasma:

2 days at 15‑25 °C

7 days at 2‑8 °C

4 weeks at (-15)‑(-25) °C

Sample stability claims were established by experimental data by the manufacturer or based on reference literature and only for the temperatures/time frames as stated in the method sheet. It is the responsibility of the individual laboratory to use all available references and/or its own studies to determine specific stability criteria for its laboratory.

", "Language": "en" } ] } }, { "ProductSpecVariant": { "MetaData": { "DocumentMaterialNumber": "07531389001", "ProductName": "CK", "ProductLongName": "Creatine Kinase", "Language": "en", "DocumentVersion": "3", "DocumentObjectID": "FF0000000596370E", "DocumentOriginID": "FF000000016CC30E", "MaterialNumbers": [ "07442017190" ], "InstrumentReferences": [ { "ID": "307", "BrandName": "cobas c 111" } ], "DisclaimerText": "Product information shown on this page contains elements of the officially released Method Sheet. If you require further information please refer to the full Method Sheet PDF under the given link, or contact your local Roche country representative." }, "Chapters": [ { "Name": "IntendedUse", "Value": "

Intended use

In vitro test for the quantitative determination of creatine kinase (CK) in human serum and plasma on the cobas c 111 system.

", "Language": "en" }, { "Name": "TestPrinciple", "Value": "

Test principle

UV‑test

Creatine phosphate + ADP

CK

creatine + ATP

ATP + D‑glucose

HK

ADP + G6P

G6P + NADP+

G6PDH

D‑6‑phosphogluconate + NADPH + H+

Equimolar quantities of NADPH and ATP are formed at the same rate. The photometrically measured rate of formation of NADPH is directly proportional to the CK activity.

", "Language": "en" }, { "Name": "MeasuringRange", "Value": "

Limits and ranges

Measuring range

7‑2000 U/L (0.12‑33.4 µkat/L)

Determine samples having higher activities via the rerun function. Dilution of samples via the rerun function is a 1:11 dilution. Results from samples diluted by the rerun function are automatically multiplied by a factor of 11.

Lower limits of measurement

Limit of Blank, Limit of Detection and Limit of Quantitation

Limit of Blank

= 7 U/L (0.12 µkat/L)

Limit of Detection

= 7 U/L (0.12 µkat/L)

Limit of Quantitation

= 7 U/L (0.12 µkat/L)

The Limit of Blank, Limit of Detection and Limit of Quantitation were determined in accordance with the CLSI (Clinical and Laboratory Standards Institute) EP17‑A2 requirements.
The Limit of Blank is the 95th percentile value from n ≥ 60 measurements of analyte-free samples over several independent series. The Limit of Blank corresponds to the concentration below which analyte-free samples are found with a probability of 95 %.
The Limit of Detection is determined based on the limit of blank and the standard deviation of low concentration samples. The Limit of Detection corresponds to the lowest analyte concentration which can be detected (value above the limit of blank with a probability of 95 %).
The Limit of Quantitation is the lowest analyte concentration that can be reproducibly measured with a precision of 20 % CV. It has been determined using low concentration creatine kinase samples.

", "Language": "en" }, { "Name": "ExpectedValues", "Value": "

Expected values

Reference intervals strongly depend on the patient group and the specific clinical situation.

For healthy people, according to Klein et al.:

LREFKlein G, Berger A, Bertholf R, et al. Abstract: Multicenter Evaluation of Liquid Reagents for CK, CK-MB and LDH with Determination of Reference Intervals on Hitachi Systems. Clin Chem 2001;47:Suppl. A30.

CK

U/L

µkat/L

Men

39‑308

0.65‑5.14

Women

26‑192

0.43‑3.21

Consensus values:

LREFThomas L, Müller M, Schumann G, et al. Consensus of DGKL and VDGH for interim reference intervals on enzymes in serum. J Lab Med 2005; 29(5):301-308.

CK

U/L

µkat/L

Men

< 190

< 3.20

Women

< 170

< 2.85

Consensus values:

LREFThomas L, Müller M, Schumann G, et al. Consensus of DGKL and VDGH for interim reference intervals on enzymes in serum. J Lab Med 2005; 29(5):301-308.

CK‑MB

U/L

µkat/L

Men/women

< 25

< 0.42

Myocardial infarction: There is a high probability of myocardial damage when the following three conditions are fulfilled:

LREFStein W. Strategie der klinischen-chemischen Diagnostik des frischen Myokardinfarktes. Med Welt 1985;36:572-577.

U/L

µkat/L

1

CKmen

> 190

> 3.17

CKwomen

> 167

> 2.79

2

CK‑MB

> 24

> 0.40

3

The CK‑MB activity accounts for 6‑25 % of the total CK‑activity.

According to Tietz:

LREFWu AHB, editor. Tietz Clinical Guide to Laboratory Tests, 4th edition. St. Louis (MO): Saunders Elsevier 2006;306-307.

CK

U/L

µkat/L

Adult males > 19 years

20‑200

0.33‑3.34

Adult females > 19 years

20‑180

0.33‑3.01

The reference values according to Klein et al. are based on the 95th percentile of a group of healthy persons (202 men and 217 women) not involved in high‑intensity athletic activities.

In order to ensure high sensitivity in the diagnosis of heart diseases the values given by Tietz are recommended. The loss of diagnostic specificity thereby incurred can be compensated for by additionally determining CK‑MB and/or troponin T. When myocardial infarction is suspected the diagnostic strategy proposals in the consensus document of European and American cardiologists should in general be followed.

LREFMyocardial Infarction Redefined - A Consensus Document of the Joint European Society of Cardiology/ American College of Cardiology Committee for the Redefinition of Myocardial Infarction. Eur Heart J 2000;21:1502-1513.

If despite the suspicion of myocardial infarction the values found remain below the stated limits, a fresh infarction may be involved. In such cases, the determinations should be repeated after 4 hours.

CK varies with physical activity level and race in healthy individuals.

LREFWu AHB, editor. Tietz Clinical Guide to Laboratory Tests, 4th edition. St. Louis (MO): Saunders Elsevier 2006;306-307.
,
LREFBlack HR, Quallich H, Gareleck CB. Racial differences in serum creatine kinase levels. Am J Med 1986;81:479-487.

Each laboratory should investigate the transferability of the expected values to its own patient population and if necessary determine its own reference ranges.

", "Language": "en" }, { "Name": "LimitationInterference", "Value": "

Limitations - interference

Criterion: Recovery within ± 10 % of initial value at a creatine kinase activity of 140 U/L (2.34 µkat/L).

Icterus:

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an I index of 60 for conjugated and unconjugated bilirubin (approximate conjugated and unconjugated bilirubin concentration: 1026 µmol/L or 60 mg/dL).

Hemolysis:

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an H index of 100 (approximate hemoglobin concentration: 62.1 µmol/L or 100 mg/dL). The level of interference may be variable depending on the exact content of erythrocytes.

Lipemia (Intralipid):

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an L index of 1000. There is poor correlation between the L index (corresponds to turbidity) and triglycerides concentration. Highly lipemic specimens (L index > 1000) may cause high absorbance flagging.

Drugs: No interference was found at therapeutic concentrations using common drug panels.

LREFBreuer J. Report on the Symposium "Drug effects in Clinical Chemistry Methods". Eur J Clin Chem Clin Biochem 1996;34:385-386.
,
LREFSonntag O, Scholer A. Drug interference in clinical chemistry: recommendation of drugs and their concentrations to be used in drug interference studies. Ann Clin Biochem 2001;38:376-385.

Cyanokit (Hydroxocobalamin) at therapeutic concentrations interferes with the test.

In very rare cases, gammopathy, in particular type IgM (Waldenström’s macroglobulinemia), may cause unreliable results.

LREFBakker AJ, Mücke M. Gammopathy interference in clinical chemistry assays: mechanisms, detection and prevention. Clin Chem Lab Med 2007;45(9):1240-1243.

For diagnostic purposes, the results should always be assessed in conjunction with the patient’s medical history, clinical examination and other findings.

ACTION REQUIRED
Special Wash Programming: The use of special wash steps is mandatory when certain test combinations are run together on the cobas c 111 analyzer. For information about test combinations requiring special wash steps, please refer to the latest version of the carry-over evasion list found with the CLEAN Method Sheet and the operator’s manual for further instructions.
Where required, special wash/carry-over evasion programming must be implemented prior to reporting results with this test.

", "Language": "en" }, { "Name": "OrderInformation", "Value": "

OrderInformation (CC Reagents - cobas + Integra)

Order information

Analyzer(s) on which kit(s) can be used

07442017190

Creatine Kinase (2 x 100 tests)

cobas c 111

Materials required (but not provided):

10759350190

Calibrator f.a.s. (12 x 3 mL)

Code 401

10759350360

Calibrator f.a.s. (12 x 3 mL, for USA)

Code 401

12149435122

Precinorm U plus (10 x 3 mL)

Code 300

12149435160

Precinorm U plus (10 x 3 mL, for USA)

Code 300

12149443122

Precipath U plus (10 x 3 mL)

Code 301

12149443160

Precipath U plus (10 x 3 mL, for USA)

Code 301

05117003190

PreciControl ClinChem Multi 1 (20 x 5 mL)

Code 391

05947626190

PreciControl ClinChem Multi 1 (4 x 5 mL)

Code 391

05947626160

PreciControl ClinChem Multi 1 (4 x 5 mL, for USA)

Code 391

05117216190

PreciControl ClinChem Multi 2 (20 x 5 mL)

Code 392

05947774190

PreciControl ClinChem Multi 2 (4 x 5 mL)

Code 392

05947774160

PreciControl ClinChem Multi 2 (4 x 5 mL, for USA)

Code 392

04774230190

NaCl Diluent 9 % (4 x 12 mL)

Code 951

", "Language": "en" }, { "Name": "SystemInformation", "Value": "

System information

CK2: ACN 550

", "Language": "en" }, { "Name": "Handling", "Value": "

Reagent handling

Ready for use

", "Language": "en" }, { "Name": "TestDefinition", "Value": "

Application for serum and plasma

cobas c 111 test definition

Measuring mode

Absorbance

Abs. calculation mode

Kinetic

Reaction direction

Increase

Wavelength A/B

340/552 nm

Calc. first/last

24-34

Unit

U/L (µkat/L)

Reaction mode

R1-S-SR

Pipetting parameters

Diluent (H2O)

R1

100 µL

-

Sample

2.75 µL

2 µL

SR

20 µL

-

Total volume

124.75 µL

", "Language": "en" }, { "Name": "StorageStability", "Value": "

Storage and stability

CK

Shelf life at 2‑8 °C:

See expiration date on reagent

On-board in use and refrigerated on the analyzer:

4 weeks

NaCl Diluent 9 %

Shelf life at 2‑8 °C:

See expiration date on reagent

On-board in use and refrigerated on the analyzer:

4 weeks

", "Language": "en" }, { "Name": "Calibration", "Value": "

Calibration

Calibrators

Calibrator f.a.s.
Deionized water is used automatically by the instrument as the zero calibrator.

Calibration mode

Linear regression

Calibration interval

Each lot and as required following quality control procedures.

Traceability: This method has been standardized against the IFCC Method for Creatine Kinase.

LREFSchumann G, Bonora R, Ceriotti F, et al. IFCC Primary Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes at 37 °C – Part 2. Reference Procedure for the Measurement of Catalytic Concentration of Creatine Kinase. Clin Chem Lab Med 2002;40(6):635-642.

", "Language": "en" }, { "Name": "Limitations", "Value": "", "Language": "en" }, { "Name": "PerformanceData", "Value": "

Specific performance data

Representative performance data on the cobas c 111 analyzer are given below. Results obtained in individual laboratories may differ.

", "Language": "en" }, { "Name": "Precision", "Value": "

Precision

Repeatability and intermediate precision were determined using human samples and controls in accordance with the CLSI (Clinical and Laboratory Standards Institute) EP5 requirements (2 aliquots per run, 2 runs per day, 21 days). The following results were obtained:

Repeatability

Mean

U/L (µkat/L)

SD

U/L (µkat/L)

CV

%

Human serum 1

94.6 (1.58)

1.0 (0.02)

1.1

Human serum 2

141 (2.35)

1.2 (0.02)

0.9

Human serum 3

320 (5.34)

2.7 (0.05)

0.9

Human serum 4

964 (16.1)

9.1 (0.15)

0.9

Human serum 5

1771 (29.6)

11 (0.18)

0.6

PCCC Multi 1*

149 (2.49)

1.4 (0.02)

1.0

PCCC Multi 2

273 (4.56)

4.0 (0.07)

1.5

Intermediate precision

Mean

U/L (µkat/L)

SD

U/L (µkat/L)

CV

%

Human serum 1

94.6 (1.58)

1.7 (0.03)

1.8

Human serum 2

141 (2.35)

2.2 (0.04)

1.5

Human serum 3

320 (5.34)

4.9 (0.08)

1.5

Human serum 4

964 (16.1)

22 (0.37)

2.2

Human serum 5

1771 (29.6)

24 (0.40)

1.4

PCCC Multi 1

149 (2.49)

1.7 (0.03)

1.2

PCCC Multi 2

273 (4.56)

4.0 (0.07)

1.5

*PCCC = PreciControl ClinChem

", "Language": "en" }, { "Name": "MethodComparison", "Value": "

Method comparison

Creatine kinase values for human serum and plasma samples obtained on the cobas c 111 analyzer (y) were compared with those determined using the corresponding reagent on a COBAS INTEGRA 400 plus analyzer (x).

Sample size (n) = 65

Passing/Bablok

LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790.

Linear regression

y = 0.972x + 10.4 U/L

y = 0.956x + 21.1 U/L

τ = 0.992

r = 0.999

The sample activities were between 7.7 and 1815 U/L (0.13 and 30.3 µkat/L).

", "Language": "en" }, { "Name": "Summary", "Value": "

Summary

Creatine kinase (CK) is a dimeric enzyme occurring in four different forms: a mitochondrial isoenzyme and the cytosolic isoenzymes CK‑MM (skeletal muscle type), CK‑BB (brain type) and CK‑MB (myocardial type).

LREFThomas L, ed. Labor und Diagnose, 8th ed. Bd 1:TH-Books Verlagsgesellschaft 2012.

The determination of CK and CK‑isoenzyme activities is utilized in the diagnosis and monitoring of myocardial infarction and myopathies such as the progressive Duchenne muscular dystrophy. Following injury to the myocardium, such as occurs with acute myocardial infarction,

LREFThomas L, ed. Labor und Diagnose, 8th ed. Bd 1:TH-Books Verlagsgesellschaft 2012.
CK is released from the damaged myocardial cells. In early cases, a rise in the CK‑activity can be found just 4 hours after an infarction.
LREFThomas L, ed. Labor und Diagnose, 8th ed. Bd 1:TH-Books Verlagsgesellschaft 2012.
,
LREFStein W. Laboratory Diagnosis of Acute Myocardial Infarction. Darmstadt: GIT Verlag 1988;34-37.
The CK activity reaches a maximum after 12‑24 hours and then falls back to the normal range after 3‑4 days.
LREFThomas L, ed. Labor und Diagnose, 8th ed. Bd 1:TH-Books Verlagsgesellschaft 2012.
,
LREFStein W. Laboratory Diagnosis of Acute Myocardial Infarction. Darmstadt: GIT Verlag 1988;34-37.

The assay method using creatine phosphate and ADP was first described by Oliver,

LREFOliver IT. A spectrophotometric method for the determination of creatine phosphokinase and myokinase. Biochem J 1955;61:116-122.
modified by Rosalki
LREFRosalki SB. An improved procedure for serum creatine phosphokinase determination. J Lab Clin Med 1967;69:696-705.
and further improved for optimal test conditions by Szasz et al.
LREFSzasz G, Gruber W, Bernt E. Creatine kinase in serum: 1. Determination of optimum reaction conditions. Clin Chem 1976;22(5):650-656.
CK is rapidly inactivated by oxidation of the sulfhydryl groups in the active center. The enzyme can be reactivated by the addition of acetylcysteine (NAC).
LREFSzasz G, Gruber W, Bernt E. Creatine kinase in serum: 1. Determination of optimum reaction conditions. Clin Chem 1976;22(5):650-656.
Interference by adenylate kinase is prevented by the addition of diadenosine pentaphosphate
LREFStandard method for the determination of creatine kinase activity. J Clin Chem Clin Biochem 1977;15:249-260.
and AMP.
LREFSzasz G, Gruber W, Bernt E. Creatine kinase in serum: 1. Determination of optimum reaction conditions. Clin Chem 1976;22(5):650-656.
,
LREFStandard method for the determination of creatine kinase activity. J Clin Chem Clin Biochem 1977;15:249-260.

Standardized methods for the determination of CK with activation by NAC were recommended by the German Society for Clinical Chemistry (DGKC)

LREFStandard method for the determination of creatine kinase activity. J Clin Chem Clin Biochem 1977;15:249-260.
in 1977 and the International Federation of Clinical Chemistry (IFCC)
LREFHørder M, Elser RC, Gerhardt M, et al. Approved Recommendation on IFCC Methods for the Measurement of Catalytic Concentration of Enzymes. Part 7. IFCC Method for Creatine Kinase. Eur J Clin Chem Clin Biochem 1991;29:435-456.
in 1991. In 2002 the IFCC confirmed their recommendation and extended it to 37 °C.
LREFSchumann G, Bonora R, Ceriotti F, et al. IFCC Primary Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes at 37 °C – Part 2. Reference Procedure for the Measurement of Catalytic Concentration of Creatine Kinase. Clin Chem Lab Med 2002;40(6):635-642.
,
LREFKlauke R, Schmidt E, Lorentz K. Recommendations for carrying out standard ECCLS procedures (1988) for the catalytic concentrations of creatine kinase, aspartate aminotransferase, alanine aminotransferase and γ-glutamyltransferase at 37 °C. Eur J Clin Chem Clin Biochem 1993;31:901-909.
The method described here is derived from the formulation recommended by the IFCC and was optimized for performance and stability.

", "Language": "en" }, { "Name": "Reagents", "Value": "

Reagents - working solutions

R1

Imidazole buffer: 123 mmol/L, pH 6.5 (37 °C); EDTA: 2.46 mmol/L; Mg2+: 12.3 mmol/L; ADP: 2.46 mmol/L; AMP: 6.14 mmol/L; diadenosine pentaphosphate: 19 µmol/L; NADP+ (yeast): 2.46 mmol/L; N‑acetylcysteine: 24.6 mmol/L; HK (yeast): ≥ 36.7 µkat/L; G6PDH (E. coli): ≥ 23.4 µkat/L; preservative; stabilizers; additives.

SR

CAPSO* buffer: 20 mmol/L, pH 8.8 (37 °C); glucose: 120 mmol/L; EDTA: 2.46 mmol/L; creatine phosphate: 184 mmol/L; preservative; stabilizers.

*CAPSO: 3‑(cyclohexylamine)‑2‑hydroxy‑1‑propanesulfonic acid

", "Language": "en" }, { "Name": "PrecautionsWarnings", "Value": "

Precautions and warnings

For in vitro diagnostic use for health care professionals. Exercise the normal precautions required for handling all laboratory reagents.

Infectious or microbial waste:
Warning: handle waste as potentially biohazardous material. Dispose of waste according to accepted laboratory instructions and procedures.

Environmental hazards:
Apply all relevant local disposal regulations to determine the safe disposal.

Safety data sheet available for professional user on request.

For USA: Caution: Federal law restricts this device to sale by or on the order of a physician.

This kit contains components classified as follows in accordance with the Regulation (EC) No. 1272/2008:

Danger

H360D

May damage the unborn child.

Prevention:

P201

Obtain special instructions before use.

P202

Do not handle until all safety precautions have been read and understood.

P280

Wear protective gloves/ protective clothing/ eye protection/ face protection/ hearing protection.

Response:

P308 + P313

IF exposed or concerned: Get medical advice/attention.

Storage:

P405

Store locked up.

Disposal:

P501

Dispose of contents/container to an approved waste disposal plant.

Product safety labeling follows EU GHS guidance.

Contact phone: all countries: +49-621-7590, USA: 1-800-428-2336

", "Language": "en" }, { "Name": "Caution", "Value": "", "Language": "en" }, { "Name": "QualityControl", "Value": "

Quality control

For quality control, use control materials as listed in the \"Order information\" section.

In addition, other suitable control material can be used.

The control intervals and limits should be adapted to each laboratory’s individual requirements. Values obtained should fall within the defined limits. Each laboratory should establish corrective measures to be taken if values fall outside the defined limits.

Follow the applicable government regulations and local guidelines for quality control.

", "Language": "en" }, { "Name": "SpecimenPreparation", "Value": "

Specimen collection and preparation

For specimen collection and preparation only use suitable tubes or collection containers.

Only the specimens listed below were tested and found acceptable.
Serum: Nonhemolyzed serum is the specimen of choice and also recommended by IFCC.
Plasma: Li‑Heparin, K2‑, K3‑EDTA plasma.

Please note: Differences in the degree of hemolysis resulting from the blood sampling procedure used can lead to deviating results in serum and plasma.

The sample types listed were tested with a selection of sample collection tubes that were commercially available at the time of testing, i.e. not all available tubes of all manufacturers were tested. Sample collection systems from various manufacturers may contain differing materials which could affect the test results in some cases. When processing samples in primary tubes (sample collection systems), follow the instructions of the tube manufacturer.

Centrifuge samples containing precipitates before performing the assay.

Stability in serum:

LREFGuder WG, Narayanan S, Wisser H, et al. List of Analytes; Preanalytical Variables. Brochure in: Samples: From the Patient to the Laboratory. Darmstadt: GIT-Verlag 1996.

2 days at 20‑25 °C

7 days at 4‑8 °C

4 weeks at -20 °C

Stability in EDTA/heparin plasma:

LREFData on file at Roche Diagnostics.

2 days at 15‑25 °C

7 days at 2‑8 °C

4 weeks at (-15)‑(-25) °C

", "Language": "en" } ] } }, { "ProductSpecVariant": { "MetaData": { "DocumentMaterialNumber": "0005168546190c701", "ProductName": "CK", "ProductLongName": "Creatine Kinase", "Language": "en", "DocumentVersion": "10", "DocumentObjectID": "FF00000005A09A0E", "DocumentOriginID": "FF0000000315BB0E", "MaterialNumbers": [ "05168546190", "05168546214" ], "InstrumentReferences": [ { "ID": "2492", "BrandName": "cobas c 702" }, { "ID": "310", "BrandName": "cobas c 701" } ], "DisclaimerText": "Product information shown on this page contains elements of the officially released Method Sheet. If you require further information please refer to the full Method Sheet PDF under the given link, or contact your local Roche country representative." }, "Chapters": [ { "Name": "IntendedUse", "Value": "

Intended use

In vitro test for the quantitative determination of creatine kinase (CK) in human serum and plasma on cobas c systems.

", "Language": "en" }, { "Name": "TestPrinciple", "Value": "

Test principle

Test principle
LREFHørder M, Elser RC, Gerhardt M, et al. Approved Recommendation on IFCC Methods for the Measurement of Catalytic Concentration of Enzymes. Part 7. IFCC Method for Creatine Kinase. Eur J Clin Chem Clin Biochem 1991;29:435-456.
,
LREFKlauke R, Schmidt E, Lorentz K. Recommendations for carrying out standard ECCLS procedures (1988) for the catalytic concentrations of creatine kinase, aspartate aminotransferase, alanine aminotransferase and γ-glutamyltransferase at 37 °C. Eur J Clin Chem Clin Biochem 1993;31:901-909.

UV‑test

Creatine phosphate + ADP

CK

creatine + ATP

ATP + D‑glucose

HK

ADP + G6P

G6P + NADP+

G6PDH

D‑6‑phosphogluconate + NADPH + H+

Equimolar quantities of NADPH and ATP are formed at the same rate. The photometrically measured rate of formation of NADPH is directly proportional to the CK activity.

", "Language": "en" }, { "Name": "MeasuringRange", "Value": "

Limits and ranges

Measuring range

7‑2000 U/L (0.117‑33.4 µkat/L)

Determine samples having higher activities via the rerun function. Dilution of samples via the rerun function is a 1:11 dilution. Results from samples diluted using the rerun function are automatically multiplied by a factor of 11.

Lower limits of measurement

Lower detection limit of the test

7 U/L (0.12 µkat/L)

The lower detection limit represents the lowest measurable analyte level that can be distinguished from zero. It is calculated as the value lying 3 standard deviations above that of the lowest standard (standard 1 + 3 SD, repeatability, n = 21).

Values below the lower detection limit (< 7 U/L) will not be flagged by the instrument.

", "Language": "en" }, { "Name": "ExpectedValues", "Value": "

Expected values

Reference intervals strongly depend on the patient group and the specific clinical situation.

For healthy people, according to Klein et al.:

LREFKlein G, Berger A, Bertholf R, et al. Abstract: Multicenter Evaluation of Liquid Reagents for CK, CK-MB and LDH with Determination of Reference Intervals on Hitachi Systems. Clin Chem 2001;47:Suppl. A30.

CK

U/L

µkat/L

Men

39‑308

0.65‑5.14

Women

26‑192

0.43‑3.21

Consensus values:

LREFThomas L, Müller M, Schumann G, et al. Consensus of DGKL and VDGH for interim reference intervals on enzymes in serum. J Lab Med 2005; 29(5):301-308.

CK

U/L

µkat/L

Men

< 190

< 3.20

Women

< 170

< 2.85

Consensus values:

LREFThomas L, Müller M, Schumann G, et al. Consensus of DGKL and VDGH for interim reference intervals on enzymes in serum. J Lab Med 2005; 29(5):301-308.

CK‑MB

U/L

µkat/L

Men/women

< 25

< 0.42

Myocardial infarction: There is a high probability of myocardial damage when the following three conditions are fulfilled:

LREFStein W. Strategie der klinischen-chemischen Diagnostik des frischen Myokardinfarktes. Med Welt 1985;36:572-577.

U/L

µkat/L

1

CKmen

> 190

> 3.17

CKwomen

> 167

> 2.79

2

CK‑MB

> 24

> 0.40

3

The CK‑MB activity accounts for 6‑25 % of the total CK‑activity.

According to Tietz:

LREFWu AHB, editor. Tietz Clinical Guide to Laboratory Tests, 4th edition. St. Louis (MO): Saunders Elsevier 2006;306-307.

CK

U/L

µkat/L

Adult males > 19 years

20‑200

0.33‑3.34

Adult females > 19 years

20‑180

0.33‑3.01

The reference values according to Klein et al. are based on the 95th percentile of a group of healthy persons (202 men and 217 women) not involved in high‑intensity athletic activities.

In order to ensure high sensitivity in the diagnosis of heart diseases the values given by Tietz are recommended. The loss of diagnostic specificity thereby incurred can be compensated for by additionally determining CK‑MB and/or troponin T. When myocardial infarction is suspected the diagnostic strategy proposals in the consensus document of European and American cardiologists should in general be followed.

LREFMyocardial Infarction Redefined - A Consensus Document of the Joint European Society of Cardiology/ American College of Cardiology Committee for the Redefinition of Myocardial Infarction. Eur Heart J 2000;21:1502-1513.

If despite the suspicion of myocardial infarction the values found remain below the stated limits, a fresh infarction may be involved. In such cases, the determinations should be repeated after 4 hours.

CK varies with physical activity level and race in healthy individuals.

LREFWu AHB, editor. Tietz Clinical Guide to Laboratory Tests, 4th edition. St. Louis (MO): Saunders Elsevier 2006;306-307.
,
LREFBlack HR, Quallich H, Gareleck CB. Racial differences in serum creatine kinase levels. Am J Med 1986;81:479-487.

Each laboratory should investigate the transferability of the expected values to its own patient population and if necessary determine its own reference ranges.

", "Language": "en" }, { "Name": "LimitationInterference", "Value": "

Limitations - interference

Criterion: Recovery within ± 10 % of initial value at a creatine kinase activity of 140 U/L (2.34 µkat/L).

Icterus:

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an I index of 60 for conjugated and unconjugated bilirubin (approximate conjugated and unconjugated bilirubin concentration: 1026 µmol/L or 60 mg/dL).

Hemolysis:

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an H index of 100 (approximate hemoglobin concentration: 62.1 µmol/L or 100 mg/dL). The level of interference may be variable depending on the exact content of erythrocytes.

Lipemia (Intralipid):

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an L index of 1000. There is poor correlation between the L index (corresponds to turbidity) and triglycerides concentration. Highly lipemic specimens (L index > 1000) may cause high absorbance flagging.

Drugs: No interference was found at therapeutic concentrations using common drug panels.

LREFBreuer J. Report on the Symposium "Drug effects in Clinical Chemistry Methods". Eur J Clin Chem Clin Biochem 1996;34:385-386.
,
LREFSonntag O, Scholer A. Drug interference in clinical chemistry: recommendation of drugs and their concentrations to be used in drug interference studies. Ann Clin Biochem 2001;38:376-385.

Cyanokit (Hydroxocobalamin) at therapeutic concentrations interferes with the test.

In very rare cases, gammopathy, in particular type IgM (Waldenström’s macroglobulinemia), may cause unreliable results.

LREFBakker AJ, Mücke M. Gammopathy interference in clinical chemistry assays: mechanisms, detection and prevention. Clin Chem Lab Med 2007;45(9):1240-1243.

For diagnostic purposes, the results should always be assessed in conjunction with the patient’s medical history, clinical examination and other findings.

ACTION REQUIRED
Special Wash Programming: The use of special wash steps is mandatory when certain test combinations are run together on cobas c systems. All special wash programming necessary for avoiding carry‑over is available via the cobas link, manual input is required in certain cases. The latest version of the carry‑over evasion list can be found with the NaOHD/SMS/SmpCln1+2/SCCS Method Sheet and for further instructions refer to the operator’s manual.

Where required, special wash/carry‑over evasion programming must be implemented prior to reporting results with this test.

", "Language": "en" }, { "Name": "OrderInformation", "Value": "

OrderInformation (CC Reagents - cobas + Integra)

Order information

Analyzer(s) on which cobas c pack(s) can be used

05168546190*

Creatine Kinase (800 tests)

System-ID 03 5923 6

cobas c 701/702

05168546214*

Creatine Kinase (800 tests)

System-ID 03 5923 6

cobas c 701/702

Materials required (but not provided):

10759350190

Calibrator f.a.s. (12 x 3 mL)

Code 401

10759350360

Calibrator f.a.s. (12 x 3 mL, for USA)

Code 401

12149435122

Precinorm U plus (10 x 3 mL)

Code 300

12149435160

Precinorm U plus (10 x 3 mL, for USA)

Code 300

12149443122

Precipath U plus (10 x 3 mL)

Code 301

12149443160

Precipath U plus (10 x 3 mL, for USA)

Code 301

05117003190

PreciControl ClinChem Multi 1 (20 x 5 mL)

Code 391

05947626190

PreciControl ClinChem Multi 1 (4 x 5 mL)

Code 391

05947626160

PreciControl ClinChem Multi 1 (4 x 5 mL, for USA)

Code 391

05117216190

PreciControl ClinChem Multi 2 (20 x 5 mL)

Code 392

05947774190

PreciControl ClinChem Multi 2 (4 x 5 mL)

Code 392

05947774160

PreciControl ClinChem Multi 2 (4 x 5 mL, for USA)

Code 392

05172152190

Diluent NaCl 9 % (119 mL)

System-ID 08 6869 3

* Some kits shown may not be available in all countries.

", "Language": "en" }, { "Name": "SystemInformation", "Value": "

System information

CK: ACN 8057

CK2: ACN 8550

", "Language": "en" }, { "Name": "Handling", "Value": "

Reagent handling

Ready for use

", "Language": "en" }, { "Name": "TestDefinition", "Value": "

Application for serum and plasma

cobas c 701/702 test definition

Assay type

Rate A

Reaction time / Assay points

10 / 27‑38

Wavelength (sub/main)

546/340 nm

Reaction direction

Increase

Units

U/L (µkat/L)

Reagent pipetting

Diluent (H2O)

R1

100 µL

R3

20 µL

Sample volumes

Sample

Sample dilution

Sample

Diluent (NaCl)

Normal

2.8 µL

Decreased

2.8 µL

15 µL

150 µL

Increased

5.6 µL

", "Language": "en" }, { "Name": "StorageStability", "Value": "

Storage and stability

CK

Shelf life at 2‑8 °C:

See expiration date on cobas c pack label.

On‑board in use and refrigerated on the analyzer:

4 weeks

On‑board on the Reagent Manager:

24 hours

Diluent NaCl 9 %

Shelf life at 2‑8 °C:

See expiration date on cobas c pack label.

On‑board in use and refrigerated on the analyzer:

4 weeks

On‑board on the Reagent Manager:

24 hours

", "Language": "en" }, { "Name": "Calibration", "Value": "

Calibration

Calibrators

S1: H2O

S2: C.f.a.s.

Calibration mode

Linear

Calibration frequency

2‑point calibration
• after reagent lot change
• as required following quality control procedures

Calibration interval may be extended based on acceptable verification of calibration by the laboratory.

Traceability: This method has been standardized against the IFCC Method for Creatine Kinase.

LREFSchumann G, Bonora R, Ceriotti F, et al. IFCC Primary Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes at 37 °C – Part 2. Reference Procedure for the Measurement of Catalytic Concentration of Creatine Kinase. Clin Chem Lab Med 2002;40(6):635-642.

", "Language": "en" }, { "Name": "Limitations", "Value": "", "Language": "en" }, { "Name": "PerformanceData", "Value": "

Specific performance data

Representative performance data on the analyzers are given below. Results obtained in individual laboratories may differ.

", "Language": "en" }, { "Name": "Precision", "Value": "

Precision

Precision was determined using human samples and controls in an internal protocol with repeatability (n = 21) and intermediate precision (3 aliquots per run, 1 run per day, 21 days). The following results were obtained:

Repeatability

Mean

U/L (µkat/L)

SD

U/L (µkat/L)

CV

%

Precinorm U

148 (2.47)

1 (0.02)

0.7

Precipath U

479 (8.00)

2 (0.03)

0.5

Human serum A

73.3 (1.22)

0.4 (0.01)

0.5

Human serum B

744 (12.4)

4 (0.1)

0.5

Human serum C

1990 (33.2)

11 (0.2)

0.5

Intermediate precision

Mean

U/L (µkat/L)

SD

U/L (µkat/L)

CV

%

Precinorm U

160 (2.67)

1.1 (0.02)

0.7

Precipath U

492 (8.20)

1.7 (0.03)

0.4

Human serum 1

183 (3.05)

2.5 (0.04)

1.4

Results for intermediate precision were obtained on the Roche/Hitachi 917 analyzer.

", "Language": "en" }, { "Name": "MethodComparison", "Value": "

Method comparison

Creatine kinase values for human serum and plasma samples obtained on a cobas c 701 analyzer (y) were compared with those determined using the corresponding reagent on a Roche/Hitachi 917 analyzer (x).

Sample size (n) = 176

Passing/Bablok

LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790.

Linear regression

y = 0.992x + 0.640 U/L

y = 0.999x - 1.25 U/L

τ = 0.991

r = 1.000

The sample activities were between 8.20 and 1953 U/L (0.137 and 32.6 µkat/L).

", "Language": "en" }, { "Name": "Summary", "Value": "

Summary

Creatine kinase (CK) is a dimeric enzyme occurring in four different forms: a mitochondrial isoenzyme and the cytosolic isoenzymes CK‑MM (skeletal muscle type), CK‑BB (brain type) and CK‑MB (myocardial type).

LREFThomas L, ed. Labor und Diagnose, 4th ed. Marburg: Die Medizinische Verlagsgesellschaft 1992.

The determination of CK and CK‑isoenzyme activities is utilized in the diagnosis and monitoring of myocardial infarction and myopathies such as the progressive Duchenne muscular dystrophy. Following injury to the myocardium, such as occurs with acute myocardial infarction

LREFThomas L, ed. Labor und Diagnose, 4th ed. Marburg: Die Medizinische Verlagsgesellschaft 1992.
, CK is released from the damaged myocardial cells. In early cases, a rise in the CK‑activity can be found just 4 hours after an infarction.
LREFThomas L, ed. Labor und Diagnose, 4th ed. Marburg: Die Medizinische Verlagsgesellschaft 1992.
,
LREFStein W. Laboratory Diagnosis of Acute Myocardial Infarction. Darmstadt: GIT Verlag 1988;34-37.
The CK‑activity reaches a maximum after 12‑24 hours and then falls back to the normal range after 3‑4 days.
LREFThomas L, ed. Labor und Diagnose, 4th ed. Marburg: Die Medizinische Verlagsgesellschaft 1992.
,
LREFStein W. Laboratory Diagnosis of Acute Myocardial Infarction. Darmstadt: GIT Verlag 1988;34-37.

The assay method using creatine phosphate and ADP was first described by Oliver

LREFOliver IT. A spectrophotometric method for the determination of creatine phosphokinase and myokinase. Biochem J 1955;61:116-122.
, modified by Rosalki
LREFRosalki SB. An improved procedure for serum creatine phosphokinase determination. J Lab Clin Med 1967;69:696-705.
and further improved for optimal test conditions by Szasz et al.
LREFSzasz G, Gruber W, Bernt E. Creatine kinase in serum: 1. Determination of optimum reaction conditions. Clin Chem 1976;22(5):650-656.
CK is rapidly inactivated by oxidation of the sulfhydryl groups in the active center. The enzyme can be reactivated by the addition of acetylcysteine (NAC).
LREFSzasz G, Gruber W, Bernt E. Creatine kinase in serum: 1. Determination of optimum reaction conditions. Clin Chem 1976;22(5):650-656.
Interference by adenylate kinase is prevented by the addition of diadenosine pentaphosphate
LREFStandard method for the determination of creatine kinase activity. J Clin Chem Clin Biochem 1977;15:249-260.
and AMP.
LREFSzasz G, Gruber W, Bernt E. Creatine kinase in serum: 1. Determination of optimum reaction conditions. Clin Chem 1976;22(5):650-656.
,
LREFStandard method for the determination of creatine kinase activity. J Clin Chem Clin Biochem 1977;15:249-260.

Standardized methods for the determination of CK with activation by NAC were recommended by the German Society for Clinical Chemistry (DGKC)

LREFStandard method for the determination of creatine kinase activity. J Clin Chem Clin Biochem 1977;15:249-260.
in 1977 and the International Federation of Clinical Chemistry (IFCC)
LREFHørder M, Elser RC, Gerhardt M, et al. Approved Recommendation on IFCC Methods for the Measurement of Catalytic Concentration of Enzymes. Part 7. IFCC Method for Creatine Kinase. Eur J Clin Chem Clin Biochem 1991;29:435-456.
in 1991. In 2002 the IFCC confirmed their recommendation and extended it to 37 °C.
LREFSchumann G, Bonora R, Ceriotti F, et al. IFCC Primary Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes at 37 °C – Part 2. Reference Procedure for the Measurement of Catalytic Concentration of Creatine Kinase. Clin Chem Lab Med 2002;40(6):635-642.
,
LREFKlauke R, Schmidt E, Lorentz K. Recommendations for carrying out standard ECCLS procedures (1988) for the catalytic concentrations of creatine kinase, aspartate aminotransferase, alanine aminotransferase and γ-glutamyltransferase at 37 °C. Eur J Clin Chem Clin Biochem 1993;31:901-909.
The method described here is derived from the formulation recommended by the IFCC and was optimized for performance and stability.

", "Language": "en" }, { "Name": "Reagents", "Value": "

Reagents - working solutions

R1

Imidazole buffer: 123 mmol/L, pH 6.5 (37 °C); EDTA: 2.46 mmol/L; Mg2+: 12.3 mmol/L; ADP: 2.46 mmol/L; AMP: 6.14 mmol/L; diadenosine pentaphosphate: 19 µmol/L; NADP+ (yeast): 2.46 mmol/L; N‑acetylcysteine: 24.6 mmol/L; HK (yeast): ≥ 36.7 µkat/L; G6PDH (E. coli): ≥ 23.4 µkat/L; preservative; stabilizers; additives.

R3

CAPSO* buffer: 20 mmol/L, pH 8.8 (37 °C); glucose: 120 mmol/L; EDTA: 2.46 mmol/L; creatine phosphate: 184 mmol/L; preservative; stabilizers.

*CAPSO: 3(‑cyclohexylamine)‑2‑hydroxy‑1‑propanesulfonic acid

R1 is in position B and R3 is in position C.

", "Language": "en" }, { "Name": "PrecautionsWarnings", "Value": "

Precautions and warnings

For in vitro diagnostic use for health care professionals. Exercise the normal precautions required for handling all laboratory reagents.

Infectious or microbial waste:
Warning: handle waste as potentially biohazardous material. Dispose of waste according to accepted laboratory instructions and procedures.

Environmental hazards:
Apply all relevant local disposal regulations to determine the safe disposal.

Safety data sheet available for professional user on request.

For USA: Caution: Federal law restricts this device to sale by or on the order of a physician.

This kit contains components classified as follows in accordance with the Regulation (EC) No. 1272/2008:

Danger

H360D

May damage the unborn child.

Prevention:

P201

Obtain special instructions before use.

P202

Do not handle until all safety precautions have been read and understood.

P280

Wear protective gloves/ protective clothing/ eye protection/ face protection/ hearing protection.

Response:

P308 + P313

IF exposed or concerned: Get medical advice/attention.

Storage:

P405

Store locked up.

Disposal:

P501

Dispose of contents/container to an approved waste disposal plant.

Product safety labeling follows EU GHS guidance.

Contact phone: all countries: +49-621-7590, USA: 1-800-428-2336

", "Language": "en" }, { "Name": "Caution", "Value": "", "Language": "en" }, { "Name": "QualityControl", "Value": "

Quality control

For quality control, use control materials as listed in the \"Order information\" section.

In addition, other suitable control material can be used.

The control intervals and limits should be adapted to each laboratory’s individual requirements. Values obtained should fall within the defined limits. Each laboratory should establish corrective measures to be taken if values fall outside the defined limits.

Follow the applicable government regulations and local guidelines for quality control.

", "Language": "en" }, { "Name": "SpecimenPreparation", "Value": "

Specimen collection and preparation

For specimen collection and preparation only use suitable tubes or collection containers.

Only the specimens listed below were tested and found acceptable.
Serum: Nonhemolyzed serum is the specimen of choice and also recommended by IFCC.
Plasma: Li‑Heparin, K2‑, K3‑EDTA plasma.

Please note: Differences in the degree of hemolysis resulting from the blood sampling procedure used can lead to deviating results in serum and plasma.

The sample types listed were tested with a selection of sample collection tubes that were commercially available at the time of testing, i.e. not all available tubes of all manufacturers were tested. Sample collection systems from various manufacturers may contain differing materials which could affect the test results in some cases. When processing samples in primary tubes (sample collection systems), follow the instructions of the tube manufacturer.

Centrifuge samples containing precipitates before performing the assay.

See the limitations and interferences section for details about possible sample interferences.

Sample stability claims were established by experimental data by the manufacturer or based on reference literature and only for the temperatures/time frames as stated in the method sheet. It is the responsibility of the individual laboratory to use all available references and/or its own studies to determine specific stability criteria for its laboratory.

Stability in serum:

LREFGuder WG, Narayanan S, Wisser H, et al. List of Analytes; Preanalytical Variables. Brochure in: Samples: From the Patient to the Laboratory. Darmstadt: GIT-Verlag 1996.

2 days at 20‑25 °C

7 days at 4‑8 °C

4 weeks at -20 °C

Stability in EDTA/heparin plasma:

2 days at 15‑25 °C

7 days at 2‑8 °C

4 weeks at (-15)‑(-25) °C

", "Language": "en" } ] } } ] }