Cardiac troponin I, cardiac troponin T, and creatine kinase MB in dialysis patients without ischemic heart disease: evidence of cardiac troponin T expression in skeletal muscle

Abstract

Serum cardiac troponin T (cTnT) concentrations are frequently increased in chronic dialysis patients as measured by the first-generation ELISA immunoassay, as is creatine kinase (CK) MB mass in the absence of acute ischemic heart disease. We designed this study to compare four serum markers of myocardial injury [CK-MB mass, first-generation ELISA cTnT, second-generation Enzymun cTnT, and cardiac troponin I (cTnI)] in dialysis patients without acute ischemic heart disease. We also evaluated skeletal muscle from dialysis patients as a potential source of serum cTnT. No patients in the clinical evaluation group (n = 24) studied by history and by physical examination, electrocardiography, and two-dimensional echocardiography had evidence of ischemic heart disease. Biochemical markers were measured in serial predialysis blood samples with specific monoclonal antibody-based immunoassays. For several patients at least one sample measured above the upper reference limit: CK-MB, 7 of 24 (30%); ELISA cTnT, 17 of 24 (71%); Enzymun cTnT, 3 of 18 (17%); and cTnI, 1 of 24 (4%). In a separate group of dialysis patients (n = 5), expression of cTnT, but not cTnI, was demonstrated by Western blot analysis in 4 of 5 skeletal muscle biopsies. Chronic dialysis patients without acute ischemic heart disease frequently had increased serum CK-MB and cTnT. The specificity of the second-generation cTnT (Enzymun) assay was improved over that of the first-generation (ELISA) assay; cTnI was the most specific of the currently available biochemical markers. cTnT, but not cTnI, was expressed in the skeletal muscle of dialysis patients.

Characteristics of a Subset of Patients With Reversible Systolic Dysfunction in Chronic Kidney Disease

“…Cardiac troponin I is specific for detection of myocardial injury in chronic renal failure as opposed to creatinine kinase enzyme levels. [12][13][14] Elevated troponin levels independently predicted increased left ventricular mass and systolic dysfunction in patients with CKD [15][16][17] with high positive predictive values for left ventricular hypertrophy and high negative predictive values for systolic dysfunction. [16][17][18] All patients in group 2 had ventricular hypertrophy, systolic dysfunction, and continued elevation of troponin I levels at follow-up.…”

Cardiac troponins T and I in patients with end‐stage renal disease: The relation with left ventricular mass and their prognostic value

“…In our study, we observed no correlation between elevated troponins and serum creatinine or BUN, which is in agreement with previous studies. 2,7,12 Since the kidney is unlikely to be responsible for the troponin clearance, it is impossible that the decreased clearance of troponin is responsible for the elevations. 9 Re-expression of the cardiac isoform of cTnT in myopathic skeletal muscle of patients with ESRD is controversial.…”

“…9 Re-expression of the cardiac isoform of cTnT in myopathic skeletal muscle of patients with ESRD is controversial. 7,8,18 Cross reactivity with skeletal muscle is unlikely, since the troponin T assay has been refined; cross reaction with skeletal muscle is not a problem with the second-and third-generation assays. 18 Troponin elevation may be due to repeated episodes of clinically silent, small MIs 8, 9 because CAD is common in these patients.…”

“…18 Troponin elevation may be due to repeated episodes of clinically silent, small MIs 8, 9 because CAD is common in these patients. However, increased cTnT is frequently encountered in patients at low risk for CAD, 2,5,7 and troponin elevations are as frequent in patients without CAD as in those with known CAD. 2,5,7,13 Our findings were not consistent with a major contribution from CAD since we excluded patients with CAD from the study.…”

“…Some studies suggest that elevation of cTnT may be due to the increased expression of cTnT in myopathic skeletal muscle in patients with renal disease. 7 The most accepted explanation is that the elevated levels of troponins reflect myocardial cell damage; however, causes of myocardial cell damage are not clear. Some suggest that troponin elevations in patients with ESRD indicate coronary artery disease (CAD).…”