Elevated values in asymptomatic patients — The appropriate use of these enzymes in patients with renal insufficiency is less clear, since elevations i

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Elevated values in asymptomatic patients — The appropriate use of these enzymes in patients with renal insufficiency is less clear, since elevations in serum troponins are commonly observed in patients with renal insufficiency who do not have clinical evidence of myocardial damage [1,2]. Although newer assays are somewhat more accurate, these tests also demonstrate increased troponin levels, particularly cTnT, in those without myocardial necrosis.

In the largest study of 733 asymptomatic patients with ESRD, an extremely high percentage had increased troponin levels, despite the use of the latest generation assays [3]; the percentages varied markedly with the utilization of different cutoff criteria:


The use of cutoff values that were greater than that observed among 99 percent of a general reference population (which were defined as 0.01 and 0.1 µg/L for cTnT and cTnI, respectively) resulted in 82 and 6 percent of dialysis patients with increases in cTnT and cTnI values, respectively.
The use of the lowest values to give 10 percent imprecision (which were 0.03 and 0.5 µg/L for cTnT and cTnI, respectively) resulted in 53 and 1 percent of patients defined as having increased values, respectively.
The use of values that had been optimized for detection of myocardial infarction (which were 0.1 and 0.6 µg/L for cTnT and cTnI, respectively) resulted in 20 and 0.4 percent of dialysis patients having increased values, respectively.

The exact mechanisms underlying these increased levels are unclear [1]. Possible reasons include elevations of troponin with left ventricular hypertrophy, endothelial dysfunction, loss of membrane integrity with leakage of the free cytosolic troponin pool, stretch-mediated troponin release, and impaired renal excretion [4]. The finding that cTnT is more frequently elevated than cTnI among asymptomatic patients with renal insufficiency may be due to the relatively higher levels of an unbound cytosolic pool of cTnT and its higher molecular weight [5].

These observations illustrate the difficulty in accurately interpreting elevations in cardiac troponins, particularly cTnT, in patients with renal insufficiency. Despite this, the measurement of specific forms of troponin may provide clinically useful information in this patient population:


Serial elevations in troponins may be diagnostically accurate in patients with suspected myocardial infarction.
Elevations in serum troponins may be highly prognostic for both short-term and long-term outcomes in asymptomatic patients as well as those presenting with suspected myocardial ischemia.

Use in prognosis

Asymptomatic patients — There is an increasing evidence that elevations in serum troponin levels in stable asymptomatic patients with ESRD are predictive of worse long-term cardiovascular outcomes and poor survival [6-17]. A 2005 meta-analysis of 28 studies consisting of 3931 asymptomatic dialysis patients noted that elevated cTnT levels were associated with a poor prognosis [13]. At a mean follow-up of 23 months, increased cTnT levels (defined as >0.1 ng/mL) were associated an increased mortality risk (RR of 2.67, 95% CI, 2.17 to 3.20). Conclusions related to increased cTnI levels could not be performed due to the wide variety of assays and different cut points.

The reasons for the association between elevated levels of troponins and a poor prognosis among asymptomatic patients with ESRD are unknown. Some reported associations include the following:


A correlation between increased troponin levels and diffuse coronary artery disease in this patient population has been reported [8,17,18]. A similar association has been reported in asymptomatic patients with chronic kidney disease who are not dialysis-dependent [19]


In a study of dialysis patients on the kidney transplant wait list, increased cTnT levels correlated with abnormal echocardiographic findings and decreased survival [16].