Cardiac Troponin T Circulates in the Free, Intact Form in Patients with Kidney Failure

Abstract

Background:The clinical significance of the increased concentrations of cardiac troponins observed in patients with end stage renal disease (ESRD) in the absence of an acute coronary syndrome (ACS) is controversial. One proposed explanation is that immunoreactive fragments of cardiac troponin T (cTnT) accumulate in ESRD. We used gel-filtration chromatography (GFC) to ascertain whether fragments of cTnT, which could cross-react in the commercial diagnostic immunoassay (Roche Diagnostics), were the cause of the increased cTnT in the serum of patients with ESRD. Methods: We subjected sera from ESRD patients (n ‫؍‬ 21) receiving dialysis and having increased cTnT concentrations to size-separation GFC. We detected cTnT in the chromatography fractions by use of the same antibodies used in the commercial assay for serum cTnT. Results: In all patients, cTnT immunoreactivity eluted as a major, homogeneous peak in an identical position between the peaks of serum prolactin [relative molecular mass (M r ) 23 000] and albumin (M r 67 000): the elution pattern of cTnT in samples obtained from ACS patients was identical to that of the ESRD patients. There was no evidence that low-molecular-mass (M r <23 000) cTnT fragments were the cause of the increased cTnT in the patients studied. Conclusions: The form of cTnT observed in the serum of patients with kidney failure and immunoreactive in the diagnostic assay is predominantly the free intact form, as in patients with ACS. Our data are consistent

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

“…Given that cTnI has a lower molecular mass than cTnT (about 22,000 vs. 37,000 Da) [129], the results reported in various studies [9,12,26,47,120,[122][123][124] indicate that there is a larger number of circulating cTnI-related molecules than cTnT-related molecules in healthy subjects. Furthermore, since cTnI and cTnT are present in the sarcomeric complex in a molecular ratio of 1:1, these differences between the circulating cTns are probably related to differences in intra- [130] or extra-cellular [131][132][133] catabolism and the peripheral turnover of cTnI and cTnT.…”

Effect of hemodialysis on traditional and innovative cardiac markers

“…Some explanations that have been provided include accumulation of immunoreactive fragments of cardiac troponins due to reduced renal clearance (15,16) or continuous cardiac release from limited areas of clinically silent myocardial necrosis (17). Other possible hypotheses are the reexpression of cTnT isoforms in the skeletal muscle fibers during uremic-induced skeletal myopathy (18), the increase of left ventricular mass index (LVMI) (19), the loss of membrane integrity, constant outflow from the free cytosolic troponin pool (20), and uremic damage on myocardial cells (21).…”

Cardiac Biomarkers in End-Stage Renal Disease

“…Diris et al (Diris et al, 2004) have shown the presence of immunoreactive cTnT fragments, which are small enough to be cleared by the kidneys and which might accumulate in ESRD patients. Others, however, have found only intact cTnT in patients with kidney failure, (Fahie-Wilson et al, 2006) and to date there is still a great deal of debate on the mechanisms underlying the cTn elevation in ESRD patients. Whatever the exact mechanism, the elevations should not be taken lightly as they are highly predictive for adverse cardiovascular events (Apple, Murakami, Pearce, & Herzog, 2002;Khan, Hemmelgarn, Tonelli, Thompson, & Levin, 2005;Sommerer, Beimler, et al, 2007).…”