Positive Troponin in CKD/ESRD: Clinical Relevance / Pearls & Pitfalls

Authors: Chris Belcher, MD, PGY-3 (@seebelcher236, Emergency Medicine Resident Physician, University of Kentucky Department of EM) and Jonathan Bronner, MD (@bronski, EM Assistant Professor and APD, University of Kentucky Department of EM) // Edited by: Alex Koyfman, MD (@EMHighAK) and Brit Long, MD (@long_brit)


A 57-year-old gentleman with a history of end stage renal disease (ESRD) presents with chest pain. The pain started this morning approximately two hours after his dialysis session. The pain was dull and left sided that didn’t radiate but was worse with movement of his left arm. He was seated watching television when the pain started. The pain was better with not moving and didn’t change with aspirin 325 mg or sublingual nitroglycerin 0.4 mg that was given en route via EMS. The pain is gone upon arrival after being present for about three hours. He’s never had pain like this before. He has no history of coronary artery disease (CAD) but takes an aspirin daily for “health”. Past medical history also includes hypertension and diabetes for which he takes insulin.

ECG shows some nonspecific T wave changes similar to prior in your system. His vital signs include BP 114/90, HR 95, RR 20, T 37°C, and oxygen saturation of 100% on the nonrebreather (NRB) that EMS administered. When you remove the NRB, his oxygen saturation is 96%. Patient used to smoke a pack per day for 10 years but quit years ago. He denies drug or alcohol use.  Chest x-ray shows bilateral tiny effusions and no other acute findings. Labs are notable for normal WBC, normal platelets, and a Hgb of 9 g/dL which is similar to prior evaluations. Electrolytes are within normal limits and BUN and Cr are elevated but lower than prior values. Troponin I is elevated at just above two times the upper limit of normal. There are no prior troponin values in your EMR.

Your astute intern asks if he should give further platelet inhibition and anticoagulate the patient for non ST-elevation myocardial infarction (NSTEMI). You re-evaluate the patient, and he’s still chest pain free and stable. Repeat ECG shows no dynamic changes. As chief resident, you advise that they should hold off given his ESRD and talk with cardiology. Cardiology advises you to trend the troponin, and they’ll likely discharge the patient if is troponin is stable. Your intern is confused. This seemed like a slam dunk diagnosis and admission. You’re waffling a bit yourself as his logic makes sense but cardiology rarely takes these elevations seriously. What should you do?


Acute coronary syndrome (ACS) is a cardiac emergency frequently encountered in the Emergency Department (ED) and encompasses the categories of ST-elevation myocardial infarction (STEMI), NSTEMI, and unstable angina. NSTEMI is defined by the elevation in serum biomarkers of myocardial necrosis (typically troponin in modern assays) without ST-elevation in patients with ischemic symptoms (1). A rise in serum troponin I (TnI) or T (TnT), with at least one value above the 99th percentile, is diagnostic for acute myocardial infarction (MI) in patients with symptoms consistent with ACS (2). Thus our patient above meets the diagnostic criteria for NSTEMI.

However,  according to the third universal definition of MI, small amounts of myocardial injury with necrosis may be detected, which are associated with congestive heart failure (CHF), renal failure, myocarditis, arrhythmias, pulmonary embolism or otherwise uneventful percutaneous or surgical coronary procedures. These should not be labeled as MI or a complication of the procedures, but rather as myocardial injury (2).

Equally confusing, low-level elevations in troponin correlate with higher risk for cardiovascular complications in renal failure, and renal failure patients may have elevations in troponin in the absence of ischemic symptoms (4). There are multiple theories as to why chronic kidney disease (CKD)/ESRD patients have elevated troponins. These include uremic skeletal myopathy, microinfarctions, left ventricular hypertrophy, decreased clearance, and unrecognized CHF (5). Little consensus is found in the literature regarding this.

What is an Emergency Physician to do with this confounding information? Below we present some pitfalls and pearls when dealing with elevated troponins in the CKD/ESRD patient.



Assuming an elevated troponin in CKD/ESRD patients does not represent ACS.


Not all CKD/ESRD patients have elevated troponins.

Do not take these elevated troponins lightly.  As above, these elevated troponins do represent higher risk for cardiovascular complications even if at a stable baseline. One study using high sensitivity troponin T (hs-cTnT) found that the adjusted hazard ratios (with 95% confidence intervals) for all-cause mortality were 2.00 (1.66 to 2.42), 2.92 (2.38 to 3.59), 4.07 (3.28 to 5.05), 6.77 (5.22 to 8.78), and 9.68 (7.18 to 13.00) in patients with hs-cTnT levels of 5 to 9, 10 to 14, 15 to 29, 30 to 49, and ≥50 ng/l, respectively, compared with patients with hs-cTnT levels <5 ng/l (6).   As stated by Freda et al (5),  “Whatever the mechanisms involved, sequential serum cardiac TnT or TnI elevation is indicative of acute myocardial damage and denotes increased risk of morbidity and mortality in patients with renal insufficiency.”  Assume ACS if the history coincides and advocate for these patients.



Not considering anginal equivalents in CKD/ESRD patients.


These patients may not exhibit typical anginal symptoms during ACS.

Consider including CKD/ESRD patients in your group of patients that present with atypical symptoms.   They may present with dyspnea, weakness or other atypical symptoms as their anginal equivalent (7).  They may even harbor “silent CAD” in which they’re asymptomatic.  One study found that 44% of a large cohort of asymptomatic hemodialysis patients had significant CAD (8).



Blaming an elevated troponin on decreased clearance.


Troponin is not likely cleared by the kidneys and is questionably dialyzable.

Troponin is a large molecule. Free TnT and bound TnT are relatively large molecules (37 and 77 kDa, respectively), similar in molecular weight to albumin (60 kDa), making it highly unlikely that the kidney would be responsible for their clearance (5).

Studies have yielded mix results regarding the dialyzability of troponin. One study from 2008 found that HD with a low flux membrane did not decrease troponins significantly but a high flux membrane did significantly decrease circulating troponin in asymptomatic patients (9). Another study from 2011 showed no difference in TnI pre and post HD (10).  This makes it difficult to generalize to all patients.  Logically, one should have not circulating troponins without underlying heart disease of some variety and we occasionally see ESRD patients without elevated troponins. As one of our wiser attendings often says, “Your kidneys don’t make troponins. This is a heart problem.”



Not utilizing troponin or not repeating troponin in these patients.


Even though it may increase time in department, obtain troponin if the clinical situation dictates and ALWAYS trend troponins in these high-risk patients.

Although they may have chronic elevation, these patients are at high risk for CAD/ACS. An acute rise in troponin is worrisome for ACS in the right clinical setting.  A significant difference is dependent upon your assay in your system but the Biochemistry Laboratory Practice Guidelines recommend a delta change of twenty percent as significant (11). This delta cannot be ascertained without obtaining troponins and trending them. Chronic elevation can also be useful for prognostication.



Not speaking with consultants on these patients.


Although you may receive push back from consultants regarding elevated troponins in your ESRD patient, these patients are high risk for CAD/ACS.

There is not robust guidance in the Cardiology (or Emergency Medicine) literature about how to manage these patients in the acute setting. Thus you should have a low threshold to get your consultant on board to help with disposition, further work up, and follow up in this high risk cohort.



Blaming the assay for the elevated troponin.


According to the National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines of 2007, Class I evidence supports measurement of cardiac troponin in renal failure patients with signs and symptoms of ACS for evaluation of MI (11).

Older studies have shown that serum troponin T was increased more frequently than troponin I in patients with renal failure, leading clinicians to question its specificity for the diagnosis of myocardial infarction (12).  Older assays had cross reactivity with skeletal muscle, lending credibility to the uremic skeletal myopathy theory (13).  However, newer assays are more cardio-specific and you should utilize your hospital’s assays for diagnosis and risk stratification in these patients (14).



Not considering other diagnoses that cause elevated troponin.


Many of the same risk factors that predispose these patients to kidney disease and CAD such as uncontrolled hypertension and diabetes also elevate the risks of other diagnoses that can lead to elevated troponin (15).

Pulmonary embolism (16) and aortic dissection (17) can lead to elevated troponins and may portend a higher mortality in pulmonary embolism. Tachyarrhythmias, sepsis, CHF, hypertensive crisis, and other entities can lead to type II NSTEMI (2). Consider other causes for an elevated troponin in this high-risk patient population.


Case Conclusion

Your intern checks on the three hour troponin repeat.  It has doubled again. You check on the patient who is still chest pain free and stable.  You immediately call cardiology who recommend heparinization, ticagrelor, and admission for further management.  Your intern feels justified and slightly less confused, and you feel relieved in getting the right care for your patient.

Take Away Points

  • CKD/ESRD patients are high risk patients for ACS/CAD.
  • An elevated troponin is not meaningless in these patients and confers higher risk of cardiovascular morbidity.
  • Always trend troponins and get consultants involved early as indicated.
  • Consider other causes of elevated troponins in this patient population.


References / Further Reading:

[1] Tintinalli, JE et al  Tintinalli’s Emergency Medicine: A Comprehensive Study Guide. 8th Ed. Chap 48 Chest pain and Chap 49 Acute Coronary Syndromes.

[2] Thygesen  K, Alpert  JS, Jaffee  AS,  et al Third universal definition of myocardial infarction. J Am Coll Cardiol. 2012; 60: 1581.

[3]  Antman  EM, Tanasijevic  MJ, Thompson  B,  et al Cardiac specific troponin I levels predict the risk of mortality in patients with acute coronary syndromes. N Engl J Med. 1996; 335: 1342.

[4] Hayashi  T, Obi  Y, Kimura  T  et al.: Cardiac troponin T predicts occult coronary artery stenosis in patients with chronic kidney disease at the start of renal replacement therapy. Nephrol Dial Transplant 23: 2936, 2008.

[5] Freda BJ, Wilson Tang WH, Van Lente F, Peacock WF, and Francis, GS. Cardiac troponins in renal insufficiency:  Review and clinical implications. Journal of the American College of Cardiology.   Volume 40, Issue 12, December 2002.

[6] Roos A, Bandstein N, Lundbäck M, Hammarsten O, Ljung R, Holzmann MJ. Stable High-Sensitivity Cardiac Troponin T Levels and Outcomes in Patients With Chest Pain. Journal of the American College of Cardiology. 2017 Oct 31;70(18):2226-2236

[7] Cai Q,. Mukku VK, Ahmad M. Coronary Artery Disease in Patients with Chronic Kidney Disease: A Clinical Update. Curr Cardiol Rev. 2013 Nov; 9(4): 331–339.

[8] deFilippi C, Wasserman S, Rosanio S, et al. Cardiac troponin T and C-reactive protein for predicting prognosis, coronary atherosclerosis, and cardiomyopathy in patients undergoing long-term hemodialysis, JAMA, 290 (2003), pp. 353-359

[9] Lippi G, Tessitore N, Montagnana M, Salvagno GL, Lupo A, Guidi GC. Influence of sampling time and ultrafiltration coefficient of the dialysis membrane on cardiac troponin I and T. Arch Pathol Lab Med. 2008 Jan;132(1):72-6.

[10] Kumar N, Michelis MF, DeVita MV, Panagopoulos G, Rosenstock JL. Troponin I levels in asymptomatic patients on haemodialysis using a high-sensitivity assay. Nephrology Dialysis Transplantation, Volume 26, Issue 2, 1 February 2011, Pages 665–670

[11] Wu AH, Jaffe AS, Apple FS, Jesse RL, Francis GL, Morrow DA et al.  NACB Writing Group National Academy of Clinical Biochemistry laboratory medicine practice guidelines: use of cardiac troponin and B-type natriuretic peptide or N-terminal proB-type natriuretic peptide for etiologies other than acute coronary syndromes and heart failure. Clin Chem. 2007 Dec;53(12):2086-96.

[12] Van Lente F, McErlean ES, DeLuca SA, Peacock WF, Rao JS, Nissen SE. Ability of troponins to predict adverse outcomes in patients with renal insufficiency and suspected acute coronary syndromes: a case-matched study. J Am Coll Cardiol. 1999 Feb;33(2):471-8

[13] McLaurin MD, Apple FS, Voss EM, Herzog CA, Sharkey SW. 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. Clin Chem. 1997 Jun;43(6 Pt 1):976-82.

[14] Nishank J and Hedayat S. How should clinicians interpret cardiac troponin values in patients with ESRD?  Semin Dial. 2011 Jul-Aug; 24(4): 398–400.

[15]  Smith C, Koyfman A, Long B.  The Elevated Troponin: What else Besides ACS could cause elevated troponin? E-article. Feb 2016. <http://www.emdocs.net/the-elevated-troponin-what-else-besides-acs-could-cause-troponin-elevation>

[16] Becattini C, Vedovati MC, Agnelli G. Prognostic value of troponins in acute pulmonary embolism: a meta-analysis. Circulation. 2007 Jul 24;116(4):427-33.

[17] Bonnefoy E, Godon P, Kirkorian G, Chabaud S, Touboul P. Significance of serum troponin I elevation in patients with acute aortic dissection of the ascending aorta. Acta Cardiol. 2005 Apr;60(2):165-70.

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