a b s t r a c t

Chest pain is one of the most common reasons for emergency department visits worldwide, and troponins play a central role in diagnosing acute coronary syndrome (ACS) in these patients. Hence, the tests for these molecules are imperative in triage for ACS. Presently, multiple high-sensitivity Troponin tests are available, including those for troponin T and I. However, in the presence of physiological and pathological alterations such as chronic kidney disease (CKD) and muscle dysfunction, these tests lose their sensitivity and specificity, especially if not interpreted in the right clinical background. Further, no guidelines exist for interpreting the results in patients with CKD. We identified studies that compared the relative efficacy, sensitivity, and specificity of tests for tropo- nin T and I in patients with CKD to understand the practical problems in the clinical interpretation of these results in the specific setting of CKD and highlight the measures to be taken into consideration.

(C) 2020

1. To the editor

Troponins are widely used to rule out acute coronary syndrome (ACS) in the emergency department, because they are intrinsic to the cardiac muscles and are released during periods of stress leading to myocardial injury. As a rule, any elevation of troponins above the assay reference range (95% confidence interval) is considered positive. This, when combined with clinical symptoms and electrocardiographic abnormalities, is used to diagnose ACS [1]. However, there are instances where troponins are found to be elevated even without ACS. The largest subset of such patients includes patients with chronic kidney disease (CKD), in whom unnecessary cardiac catheterizations that require nephrotoxic contrast must be avoided.

Studies have shown that in patients with end-stage renal disease who are not on dialysis and do not have ACS, the prevalence of positive troponin T (TnT) is 39% to 68%; while the prevalence of positive tropo- nin I (TnI) is only 3% to 38% by high-sensitive (hs) assays [2]. For pa- tients on dialysis (either hemodialysis or Peritoneal dialysis) who do not have ACS, the prevalence of positive TnT is 39% to 98% and positive TnI is 3% to 67.4% by hs assays [2]. Thus, even though both types of tro- ponins are elevated, the prevalence of elevated TnT is greater than TnI. A study by Kraus et al. showed that the specificity of hs-assay TnT for di- agnosing ACS was 73% without renal dysfunction, but in patients with

* Corresponding author at: Division of Cardiology, Department of Medicine, New York Medical College – Metropolitan Hospital Center, 1901 First Avenue, Room 704, New York, NY 10029, United States of America.

E-mail address: [email protected] (T. Kansara).

CKD, the specificity dropped to 26% [3]. A study by Abbas et al. showed that with the progression of CKD, the prevalence of TnT and TnI increased, but at each stage the prevalence of TnT was much higher than that of TnI [4].

The explanation for the above data lies in the metabolism and excre- tion of troponins. TnT is excreted almost exclusively by the kidneys, while TnI is excreted by the liver and kidneys. As a result, in conditions of renal dysfunction, TnT may be positive because of failure of excretion, even though its production is normal. Another etiology for elevated tro- ponins in patients with CKD includes left ventricular hypertrophy, which causes stress on cardiac muscles, leaking small amounts of tropo- nins in the serum (a term called “non-thrombotic leak”). This chroni- cally elevated troponin reduces the sensitivity of the test to rule out ACS. However, this leak is constant and does not show serial changes.

A rise/fall in troponin levels (by 20%) helps in the diagnosis of ACS.1 Kraus et al. showed that to maintain a specificity between 85% and 90%, the troponin should be elevated to 280% for TnI and 250% for TnT in patients with CKD [3].

With renal dysfunction, diagnostic cardiac catheterization poses a greater risk because of contrast utilization. As the prevalence of chroni- cally elevated TnI is less than TnT in patients with renal dysfunction, in our practice, we prefer TnI over TnT to rule out ACS. Regardless, with a higher prevalence of false positive troponins, physicians must be dili- gent to include the recommendation for serial monitoring of troponins with serial electrocardiograms prior to an invasive strategy in patients with CKD.

https://doi.org/10.1016/j.ajem.2020.12.051

0735-6757/(C) 2020

T. Kansara, M. Majmundar, C. Basman et al. American Journal of Emergency Medicine 41 (2021) 14–15

References

1. Thygesen K, Alpert J, Jaffe A, et al. What’s new in the fourth Universal Definition of Myocardial Infarction? Eur Heart J. 2018;39(42):3757-8. https://doi.org/10.1093/ eurheartj/ehy655.
2. Arnadottir A, Klein CF, Iversen K. Head-to-head comparison of Cardiac troponin T and troponin I in patients without acute coronary syndrome: a systematic review. Biomarkers. 2017;22(8):701-8. https://doi.org/10.1080/1354750x.2017.1335779.
3. Kraus D, Jeinsen BV, Tzikas S, et al. cardiac troponins for the diagnosis of acute myo- cardial infarction in chronic kidney disease. J Am Heart Assoc. 2018;7(19). https://doi. org/10.1161/jaha.117.008032.
4. Abbas NA, John RI, Webb MC, et al. Cardiac troponins and renal function in nondialysis patients with chronic kidney disease. Clin Chem. 2005;51(11):2059-66. https://doi.org/10.1373/clinchem.2005.055665.

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