Troponin T release in hemodialysis patients.

To the Editor: We read with interest the recent article by Diris et al1 investigating the reason for elevated serum concentrations of cardiac troponin T (cTnT) in hemodialysis patients. The authors found variable amounts of different cTnT fragments in the blood of hemodialysis patients, ranging in size from 8 to 25 kDa. In contrast, intact cTnT (39 kDa) was found only in the cTnT-spiked, pooled serum from healthy subjects. Median concentrations of cTnT increased significantly with longer duration of hemodialysis. From these findings, the authors speculated that in vivo fragmentation of cTnT occurs only in hemodialysis patients and that impaired renal function causes the unexplained accumulation of these fragments in blood. The authors further hypothesized that elevated cTnT is not the result of a cardiac troponin T release due to impaired hemodynamics or underlying cardiac disease but is rather the result of accumulating cTnT fragments from small amounts of troponin released continuously from physiological cardiomyocyte decay. We believe that these conclusions are not justified for several reasons, as follows. First, Western blot is extremely sensitive to accumulation and nonspecific binding of antibodies on the electrophoresis gel. However, information on the specificity of the monoclonal mouse antibody prepared from clone 4C5 (Fortron) has not been provided. Thus, it may be that not cardiac but skeletal troponin T is identified by the antibodies. It may even be that it is not cTnT fragments at all that are detected. Properly designed experimental investigation would have required amino acid sequencing of the protein bands on Western blot. Such an analysis is a standard procedure in proteomic research and definitely required before an interpretation is allowed on the protein nature of antibody staining in Western blot. Second, we agree with the authors that renal dysfunction impairs the clearance of intact cTnT from blood, resulting in an amplification of the marker concentration in blood.2 We also agree that there might be a continuous release of cardiac constituents in healthy persons, but this is not yet measurable with current assay formats. However, we disagree with the hypothesis that elevated cTnT in hemodialysis patients is due to the accumulation of a physiological troponin release after microloss of myocytes. Patients with end-stage renal disease are not healthy subjects by definition. A consistent body of evidence from large observational trials has established beyond doubt that cTnT concentrations are inversely related to prognosis in patients with end-stage renal disease.3,4 Thus, increasing concentrations of cTnT with duration of hemodialysis support the concept of progressive cardiac or coronary disease and the prevalence of complex lesion morphology and multiple comorbid conditions such as diabetes, hypertension, congestive heart failure, a history of previous myocardial infarction, or a history of previous coronary artery bypass grafting5 rather than the concept of a time-dependent accumulation of cTnT fragments. How could the authors otherwise explain the increased mortality and cardiac morbidity associated with cTnT at the lowest detectable range?3,4 The authors seemingly ignore the important clinical information and may mislead the readers by unconfirmed and inaccurately conducted Western blot analyses. This may prevent responsible physicians from reacting to elevated cTnT levels in hemodialysis patients. Also, the reasoning that minor elevations of cTnT in the presence of normal CK-MB mass “are unlikely due to recent myocardial ischemia” is in contrast with accumulated scientific evidence from large clinical trials. Evangelos Giannitsis, MD Hugo A. Katus, MD Medizinische Klinik Abtlg Innere Medizin III Universitaetsklinikum Heidelberg Heidelberg, Germany Prof Katus invented the troponin T assay and holds a patent jointly with Roche Diagnostics, Germany.