Clinical and analytical evaluation of kits for measurement of creatine kinase isoenzyme MB.

Abstract We studied the analytical and clinical performance of six methods for creatine kinase (EC 2.7.3.2) isoenzyme MB (CK-MB): three immunoassays (Behring, Hybritech, and International Immunoassay Labs); one immunoinhibition assay (Roche); one immunoinhibition/column method (Du Pont); and one electrophoretic method (Beckman). Between-day precision for all kits was poor at the upper reference limit. All methods gave results linearly related to CK-MB concentration and all were free from CK-MM, CK-BB, and adenylate kinase interference. Only the Du Pont method was adversely affected by atypical isoenzymes. For diagnosis of acute myocardial infarction in a coronary care population (n = 40; prevalence = 45%), all methods were approximately 95% efficient, when appropriate reference criteria were used. Some manufacturers fail to provide data for an appropriate (acutely ill, non-infarct) reference population; decreased diagnostic specificity may result from use of reference ranges based on results for healthy subjects. Expression of CK-MB as a percent of total CK degrades efficiency unless total CK is markedly increased.

Download Full-text

A sensitive bioluminescent immunoinhibition test for CK-B subunit activity and a CK-MB specific ELISA compared: correlation with agarose electrophoresis and influence of CK-isoenzyme profile on results.

Clinical Chemistry ◽

10.1093/clinchem/34.7.1474 ◽

1988 ◽

Vol 34 (7) ◽

pp. 1474-1478 ◽

Cited By ~ 2

Author(s):

F Gorus ◽

V Claessens ◽

P Goubert ◽

M Laureys

Keyword(s):

Creatine Kinase ◽

Regression Analysis ◽

Linear Regression Analysis ◽

Test Results ◽

Electrophoretic Method ◽

Reference Limit ◽

B Subunit ◽

Highly Sensitive ◽

Agarose Electrophoresis ◽

Upper Reference Limit

Abstract Searching for alternatives to the imprecise spectrophotometric tests for low-concentration creatine kinase (EC 2.7.3.2) isoenzyme MB (CK-MB), we investigated the analytical performance of two potentially superior approaches--a bioluminescent immunoinhibition assay (I, LKB-Wallac) and an ELISA (enzyme-labeled immunosorbent assay) technique (II, Hybritech)--in comparison with an electrophoretic method (III, Beckman). Only I showed good between-day precision (CV 8.3%) at the upper reference limit, allowing reproducible assay of CK-B subunit activity down to at least 3 U/L. In conditions where CK isoenzyme assays remained unaffected by CK-MM concentrations, test results were proportional to the amount of CK-MB in the sample up to at least 50 U/L for I, 120 micrograms/L for II, and 100 U/L for III (r greater than 0.998 by linear regression analysis). For CK-MB-positive samples, the data by I correlated more closely with values by III (n = 24; r = 0.994) than did results by II (n = 15; r = 0.909), but both methods were equally effective in discriminating between samples with or without electrophoretically supranormal CK-MB activity (93% sensitivity). II was entirely CK-MB specific, whereas CK-B activity by I was consistently (18/18) increased in CK-MB-negative samples containing CK-BB (n = 6; r = 0.996) or macro CK, types 1 or 2 (n = 12; r = 0.930). I is highly sensitive for screening for increased non-MM CK activity, the nature of which should be subsequently clarified by electrophoresis.

Download Full-text

Multicenter harmonization of common enzyme results by fresh patient-pool sera

Clinical Chemistry ◽

10.1093/clinchem/44.3.614 ◽

1998 ◽

Vol 44 (3) ◽

pp. 614-621 ◽

Cited By ~ 6

Author(s):

Paul F H Franck ◽

Gerard Steen ◽

Arnold J P F Lombarts ◽

John H M Souverijn ◽

Robert K A van Wermeskerken

Keyword(s):

Creatine Kinase ◽

Certified Reference Materials ◽

Parametric Method ◽

Reference Population ◽

Reference Laboratory ◽

Reference Ranges ◽

Clinical Laboratories ◽

Individual Laboratory ◽

The Individual ◽

Regional Reference

Abstract A region consisting of 19 clinical laboratories harmonized their calibration of seven common enzymes by using fresh patient-pool sera. One of the laboratories was chosen to act as Regional Reference Laboratory (RRL). This laboratory used internationally accepted (mostly IFCC) methods at 37 °C, with an intralaboratory CV ≤2.5%. First, the reference ranges of the RRL were verified by analysis of a reference population and calculation of the results by a parametric method. Next, all laboratories, including the RRL, received six patient-pool sera and analyzed them at the same time on the same date. Enzyme calibration factors at each laboratory were converted on the basis of the slope, and occasionally the intercept, of regression analysis with the RRL and the individual laboratory. Before harmonization, the interlaboratory CVs varied from 16.9% to 61.6%. After harmonization, CVs decreased to between 5.0% and 9.5%. These results proved to be reproducible over a period of more than a year. Using internationally accepted inaccuracy and imprecision criteria, the achieved interlaboratory CVs permit the use of one set of reference ranges by all participating laboratories. Certified Reference Materials were analyzed, resulting in interlaboratory CVs as low as those achieved with patient-pool sera. These materials can act as commutable reference preparations, except for creatine kinase.

Download Full-text

Sampling from a skewed population distribution as exemplified by estimation of the creatine kinase upper reference limit.

Clinical Chemistry ◽

10.1093/clinchem/30.1.18 ◽

1984 ◽

Vol 30 (1) ◽

pp. 18-23 ◽

Cited By ~ 20

Author(s):

W G Miller ◽

V M Chinchilli ◽

H D Gruemer ◽

W E Nance

Keyword(s):

Mathematical Model ◽

Creatine Kinase ◽

Adult Female ◽

Parametric Analysis ◽

Population Distribution ◽

Male And Female ◽

Reference Limit ◽

Mathematical Formulas ◽

Upper Reference Limit ◽

Larger Sample

Abstract Creatine kinase (EC 2.7.3.2) was measured in sera from 580 females, ages 1-77 years, and 550 males, ages 1-63 years. The distribution of results for male and female groups shows pronounced skewing toward higher values. The observed distribution of results could not be described by any of six mathematical formulas for skewed distributions, an indication of the unsuitability of such formulas to transform these data for parametric analysis. The range of 97.5 percentile estimates produced by six independent samples of 100, 200, and 400 observations randomly selected from a mathematical model defined by the adult female distribution showed progressive narrowing from the 150-380 U/L interval for the samples of 100 observations to 200-265 U/L for the samples of 400 observations; no further improvement was seen when 800 observations were used. The samples of 100 and 200 observations contained extreme value points that might appear as "outliers" but were shown to be valid members of the population distribution when larger sample sizes were collected.

Download Full-text

Clinical evaluation of immunoinhibition determination of creatine kinase B subunits in coronary care.

Clinical Chemistry ◽

10.1093/clinchem/29.2.353 ◽

1983 ◽

Vol 29 (2) ◽

pp. 353-355 ◽

Cited By ~ 1

Author(s):

J Booth ◽

P J McCarthy ◽

R N Walmsley

Keyword(s):

Creatine Kinase ◽

Chest Pain ◽

Normal Values ◽

Clinical Findings ◽

Reference Ranges ◽

B Subunit ◽

Creatine Kinase B ◽

Coronary Care ◽

Total Creatine

Abstract One hundred patients with chest pain of cardiac origin were evaluated on the basis of clinical findings, electrocardiograph results, and total creatine kinase (CK) and creatine kinase B-subunit (CK-B) activity (as determined by immunoinhibition with the Boehringer CK-MB kit) in serum. All patients diagnosed as having had an acute myocardial infarction had increased values for both CK-B and total CK. In no case was normal total CK activity associated with an increased CK-B, nor was normal CK-B associated with an increased total CK. During collection of data for reference ranges, we found 10 patients who had no evidence of cardiac disease but had various other diseases, who exhibited high values for CK-B in serum; four of these had normal values for total CK. We conclude that estimations of CK-B in serum by this method added no more diagnostic information than did data on total CK in the evaluation of chest pain.

Download Full-text

Albumin and calcium reference interval using healthy individuals and a data-mining approach

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/0004563220944204 ◽

2020 ◽

Vol 57 (5) ◽

pp. 373-381 ◽

Cited By ~ 2

Author(s):

N Jassam ◽

A Luvai ◽

D Narayanan ◽

D Turnock ◽

G Lee ◽

...

Keyword(s):

Metrological Traceability ◽

Reference Interval ◽

Reference Population ◽

Reference Intervals ◽

Healthy Individuals ◽

Reference Limit ◽

Common Reference ◽

Age Related ◽

Upper Reference Limit ◽

Analytical Platforms

Background Harmonization of reference intervals for analytes that have a sound calibration and metrological traceability is a widely recommended practice. The UK Pathology Harmony has recently harmonized reference intervals for calcium and albumin. In this study, we have determined the reference intervals for calcium and albumin on the UK’s most commonly used analytical platforms. Method A prospective reference population of healthy individuals was recruited according to the IFCC CRIDL criteria. A second indirect population was collected from 14 primary care setting and measured in laboratories using various analytical platforms and methods (Roche, Abbott, Beckman and Siemens analytical platforms). Results In total, 299 subjects were recruited; the central 95th centile values for calcium for three out of four analytical platforms were in a close agreement with UK Pathology Harmony reference intervals of 2.2–2.6 mmol/L. Reference intervals of BCG methods from both cohorts and irrespective of analytical platforms were higher for both lower and upper reference limits than those for BCP. In comparison, the indirect study showed an age-related variation. The younger population reference intervals varied by up to 5.7% at the lower reference limit and up to 12% at the upper reference limit compared with Pathology Harmony reference intervals, and the older population showed a variation of up to 14% at both limits. Conclusion While calcium reference intervals can be a subject for harmonization, albumin reference intervals studied showed large variation which is unsupportive of embracing a common reference interval for albumin.

Download Full-text

Mass concentration and activity concentration of creatine kinase isoenzyme MB compared in serum after acute myocardial infarction

Clinical Chemistry ◽

10.1093/clinchem/36.1.149 ◽

1990 ◽

Vol 36 (1) ◽

pp. 149-153 ◽

Cited By ~ 14

Author(s):

J R Delanghe ◽

A M De Mol ◽

M L De Buyzere ◽

I K De Scheerder ◽

R J Wieme

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Creatine Kinase ◽

Catalytic Activity ◽

Conformational Changes ◽

Mass Concentration ◽

Activity Concentration ◽

Steady Increase ◽

Reference Limit ◽

Upper Reference Limit

Abstract We compared three current methods (immunoinhibition, "Isomune-CK" immunoprecipitation, and the Tandem-E CKMB II immunoenzymometric assay) for determination of creatine kinase (CK; EC 2.7.3.2) isoenzyme MB in serum. Although results inter-correlated well, the immunoinhibition assay gave higher activity values. Atypical CK forms did not interfere with the immunoprecipitation and immunoenzymometric methods. In acute myocardial infarction the catalytic properties of CK decreased with the enzyme's age, as reflected by a steady increase in activation energy of the catalyzed reaction. In septicemia patients with very low CK and CK-MB catalytic activity, mean CK-MB mass concentration exceeded the upper reference limit, suggesting an increased rate of loss of activity concentration in these patients' sera. Because of the assay's lesser susceptibility to conformational changes at the active site of the enzyme, we suggest that measurement of CK-MB mass concentration is better suited for infarct sizing than measurement of catalytic activity.

Download Full-text

The 99th percentile of reference population for cTnI and cTnT assay: methodology, pathophysiology and clinical implications

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2016-0933 ◽

2017 ◽

Vol 55 (11) ◽

Cited By ~ 18

Author(s):

Aldo Clerico ◽

Martina Zaninotto ◽

Andrea Ripoli ◽

Silvia Masotti ◽

Concetta Prontera ◽

...

Keyword(s):

Task Force ◽

Clinical Decision ◽

Reference Population ◽

Clinical Implications ◽

Factors Affecting ◽

Reference Limit ◽

Physiological Variables ◽

Mathematical Algorithms ◽

Regulatory Bodies ◽

Upper Reference Limit

AbstractAccording to recent international guidelines, including the 2012 Third Universal Definiton of Myocardial Infarction by the Joint ESC/ACCF/AHA/WHF Task Force, an increase in cardiac troponin (cTn) levels over the 99th percentile upper reference limit (99th URL) should be considered clinically relevant, this cut-off being measured with an imprecision ≤10 CV%. In theory 99th URL values strongly depend not only on demographic and physiological variables (i.e. criteria for considering the reference population “healthy”), but also on the analytical performance of cTn methods and mathematical algorithms used for the calculation. The aim of the present article was therefore to review the methodological and pathophysiological factors affecting the evaluation and calculation of the 99th URL for cTn assay. The critical analysis made showed that no uniform procedure is followed, and nor have experts or regulatory bodies provided uniform guidelines for researchers or cTn assays manufacturers as an aid in “their quest to define normality”. In particular, little attention has been paid to the way in which a healthy reference population is to be selected, or the criteria for calculating the 99th URL value for cTn assays, thus highlighting the need for international recommendations not only for demographic and physiological variables criteria for defining a healthy reference population, but also for calculating mathematical algorithms for establishing/calculating clinical decision values. An expert consensus group, comprising laboratory and clinical scientists, biomedical statisticians, industrial and regulatory representatives, should be responsible for drawing up these guidelines.

Download Full-text

99th percentile upper reference limit of AccuTnI+3 in a Korean reference population: a multicenter study using fresh serum

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2019-0189 ◽

2019 ◽

Vol 57 (11) ◽

pp. e282-e284 ◽

Cited By ~ 1

Author(s):

Soo Young Moon ◽

Namhee Kim ◽

Sun Min Lee ◽

Shinae Yu ◽

Kyung Ran Jun ◽

...

Keyword(s):

Multicenter Study ◽

Reference Population ◽

Reference Limit ◽

Fresh Serum ◽

Upper Reference Limit

Download Full-text

Radioimmunoassay of serum myoglobin: evaluation and modification of a commercial kit and assessment of its usefulness for detecting acute myocardial infarction.

Clinical Chemistry ◽

10.1093/clinchem/24.11.2047 ◽

1978 ◽

Vol 24 (11) ◽

pp. 2047-2049 ◽

Cited By ~ 11

Author(s):

N P Kubasik ◽

W Guiney ◽

K Warren ◽

J P D'Souza ◽

H E Sine ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Creatine Kinase ◽

Care Facility ◽

Medical Systems ◽

Normal Ranges ◽

Coronary Care ◽

Commercial Kit ◽

Creatine Kinase Isoenzyme Mb ◽

Serum Myoglobin

Abstract We evaluated a modified procedure for a commercially available myoglobin radioimmunoassay kit (Nuclear Medical Systems). Within-run and run-to-run precision was acceptable. Normal ranges were established and paralelism studies performed. Clinical usefulness was assessed in 100 consecutive patients admitted to our coronary-care facility. The determinations were done daily, along with creatine kinase and its isoenzymes, and lactate dehydrogenase and its isoenzymes. Fifty of the 100 patients ultimately were shown to have had acute myocardial infarction. Myoglobinemia was present in most of the patients with acute myocardial infarction, but information on its presence was less usefull clinically than was detection of creatine kinase isoenzyme MB.

Download Full-text

Multicenter Evaluation of an Automated Assay for Troponin I

Clinical Chemistry ◽

10.1093/clinchem/48.6.869 ◽

2002 ◽

Vol 48 (6) ◽

pp. 869-876 ◽

Cited By ~ 82

Author(s):

Denise Uettwiller-Geiger ◽

Alan HB Wu ◽

Fred S Apple ◽

Anthony W Jevans ◽

Per Venge ◽

...

Keyword(s):

Detection Limit ◽

Troponin I ◽

Reference Population ◽

Reference Limit ◽

Automated Assay ◽

Heparin Plasma ◽

Edta Plasma ◽

Upper Reference Limit ◽

Matched Samples ◽

Assay Interference

Abstract Background: Cardiac troponin I (cTnI) is a powerful tool to aid in the diagnosis of myocardial infarction and cardiac muscle damage. We describe an assay that overcomes problems of early assays that were often affected by cTnI degradation, assay interference, poor sensitivity, and imprecision. Methods: The analytical performance of the Access® AccuTnITM assay (Beckman Coulter) was evaluated at five institutions. Controls, zero calibrator, and diluted patient samples were used to determine precision, detection limit, functional sensitivity, and linearity. The 97.5 and 99 percentiles of a reference population were determined. Common interferents and heterophilic patient samples were tested. Equimolarity was determined by assaying samples with various ratios of free and complexed cTnI. Matched samples drawn into serum, EDTA, lithium heparin, and sodium heparin sample tubes were compared. Results: Total imprecision (CVs) was 4.0–8.8% between 0.40 and 31 μg/L cTnI. The detection limit was <0.01 μg/L. The 97.5 percentile upper reference limit (URL) was 0.03 μg/L (CV = 20%), and the 99 percentile URL was 0.04 μg/L (CV = 14%). Total CVs of 10% and 20% were seen at and above 0.06 and 0.03 μg/L, respectively. The assay was linear to >60 μg/L and not affected by common assay interferents. An equimolar response was observed with free, complexed, phosphorylated, and dephosphorylated forms of cTnI. Results were 4% lower in serum and 14% lower in EDTA plasma than in lithium heparin plasma (P <0.01), independent of cTnI concentration. Conclusion: AccuTnI is a sensitive and precise assay for the measurement of cTnI.

Download Full-text