Clinical specificity of a second-generation cardiac troponin T assay in patients with chronic renal failure

Abstract We report on the evaluation of the second-generation assay for cardiac troponin T (cTnT) on the Enzymun®system. This new assay is completely specific for the cardiac isoform of TnT, utilizing two cardiospecific monoclonal antibodies. The assay time is reduced to 45 min. The interassay precision shows a median CV of 5.5%; 20% interassay CV was found between 0.05 and 0.1 μg/L. The cardiosensitivity of the second-generation cTnT assay in patients with ischemic myocardial injury appears equivalent when compared with the first-generation assay. We found no falsely positive results in patients with skeletal muscle damage including multitraumas, surgery patients, and marathon runners who showed highly increased values with the unspecific first-generation assay. In Duchenne disease cTnT was still increased, but to a much lower extent. cTnT remains increased in renal failure, but to a lesser degree than with the first-generation assay. The cause of this increase remains unclear. Although a cross-reactivity of skeletal muscle TnT in the second-generation assay could be excluded by our findings, minor myocardial damage or expression of the cardiac isoform of TnT in regenerating muscles cannot be ruled out in those cases with apparently falsely increased cTnT values. The second-generation cTnT assay is a step forward in the combination of cardiosensitivity and cardiospecificity in biochemical markers for diagnosis of heart disease.

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Multisite Study of a Second Generation Whole Blood Rapid Assay for Cardiac Troponin T

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/000456329903600406 ◽

1999 ◽

Vol 36 (4) ◽

pp. 438-446 ◽

Cited By ~ 3

Author(s):

H. M. E. Azzazy ◽

S.-H. Duh ◽

R. L. Fitzgerald ◽

R. W. McLawhon ◽

M. Rosenthal ◽

...

Keyword(s):

Whole Blood ◽

Cardiac Troponin ◽

Second Generation ◽

Troponin T ◽

Cardiac Troponin T ◽

Rapid Assay

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Cardiac troponin T isoforms expressed in renal diseased skeletal muscle will not cause false-positive results by the second generation cardiac troponin T assay by Boehringer Mannheim

Clinical Chemistry ◽

10.1093/clinchem/44.9.1919 ◽

1998 ◽

Vol 44 (9) ◽

pp. 1919-1924 ◽

Cited By ~ 129

Author(s):

Vincent Ricchiuti ◽

Ellen M Voss ◽

Arthur Ney ◽

Mark Odland ◽

Page A W Anderson ◽

...

Keyword(s):

Skeletal Muscle ◽

Molecular Mass ◽

Cardiac Troponin ◽

Second Generation ◽

Troponin T ◽

Chronic Renal Disease ◽

Polyacrylamide Gel Electrophoresis ◽

Sodium Dodecyl ◽

Cardiac Troponin T ◽

Muscle Biopsies

Abstract The purpose of this study was to determine whether the two monoclonal anti-cardiac troponin T (cTnT) antibodies (MAbs) used in the second generation cTnT assay by Boehringer Mannheim (BM, capture Ab, M11.7; detection Ab, M7) would detect cTnT isoforms expressed in human skeletal muscle in response to chronic renal disease (CRD). cTnT expression was examined in skeletal muscle biopsies obtained from 45 CRD patients, as well as nondiseased human heart (n = 3) and skeletal muscle (n = 3). cTnT proteins were resolved by modified 7.5% sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred to nitrocellulose, and probed with the following anti-cTnT MAbs: M11.7; M7; JS-2, Lakeland Biomedical; and 13–11, Duke University. All four antibodies detected the cTnT isoforms (Ta, Te) expressed in human myocardium. In 20 of 45 skeletal muscle biopsies, MAb M11.7 recognized its epitope in one to three proteins, molecular mass 34–36 kDa, designated Te, Td, and Tc; the strongest signal was that of Te. The same proteins were recognized by MAbs JS-2 and 13–11. The BM M7 antibody did not detect the cTnT isoforms in the molecular mass range of 34–36 kDa. However, MAb M7 did detect a cTnT isoform, molecular mass 39 kDa, in 2 of 45 biopsies. This isoform had an electrophoretic mobility similar to the predominant heart cTnT isoform, Ta. We conclude that cTnT isoforms are expressed in the skeletal muscle of CRD patients. However, given the epitopes recognized by the BM MAbs M7 and M11.7 and the variable presence of these cTnT isoforms in skeletal muscle, the second generation BM cTnT assay will not detect these isoforms if they are released from skeletal muscle into the circulation.

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Cardiac Troponin T and Creatine Kinase MB Are Not Increased in Exterior Oblique Muscle of Patients with Renal Failure

Clinical Chemistry ◽

10.1093/clinchem/47.6.1023 ◽

2001 ◽

Vol 47 (6) ◽

pp. 1023-1030 ◽

Cited By ~ 14

Author(s):

Salim Fredericks ◽

Joanne F Murray ◽

Michael Bewick ◽

René Chang ◽

Paul O Collinson ◽

...

Keyword(s):

Skeletal Muscle ◽

Renal Failure ◽

Creatine Kinase ◽

Cardiac Troponin ◽

Troponin T ◽

Oblique Muscle ◽

Cardiac Troponin T ◽

Healthy Controls ◽

Creatine Kinase Mb ◽

Significant Difference

Abstract Background: Serum cardiac troponin T (cTnT) concentrations may be increased in patients with renal dysfunction without evidence of cardiac damage, as assessed by conventional methods. It has been suggested that these positive measurements result from the expression in skeletal muscle of fetal isoforms of cTnT, which are detected by the cTnT immunoassay. Methods: Skeletal muscle (exterior oblique) biopsies were taken from healthy living kidney donors (n = 5) and transplant recipients (n = 19). The amounts of cTnT and creatine kinase (CK) isoenzymes in skeletal muscle of healthy controls were compared with those in patients with renal failure (Wilcoxon–Mann–Whitney test). cTnT was measured quantitatively by a second-generation assay, with a limit of detection of 1 μg/g of protein, and qualitatively by immunohistochemistry and immunoblotting. CK-MB was measured by quantitative electrophoresis. Results: Minute quantities of cTnT were detected in 2 of the 5 (40%) control samples and 9 of the 19 (47%) renal failure samples, respectively, at mean concentrations of <5 μg/g of protein for both subject groups. This was <1/6000th that found in heart muscle. There was no significant difference in cTnT or CK-MB content in skeletal muscle between healthy controls and patients with renal failure. Increased serum cTnT did not predict detectable cTnT in skeletal muscle. cTnT was not detected qualitatively by immunoblotting or immunohistochemistry in any skeletal muscle samples. Conclusions: Uremia does not affect the content of cTnT or CK-MB in exterior oblique muscle, suggesting that cTnT detected in serum from patients with renal failure does not originate from skeletal muscle.

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