Utility of traditional circulating and imaging-based cardiac biomarkers in patients with predialysis CKD

Abstract

Cardiac biomarkers, such as cardiac troponin T (cTnT), brain natriuretic peptide (BNP), and N-terminal-pro-BNP (NT-pro-BNP), are commonly used to diagnose acute coronary syndrome and congestive heart failure exacerbation in symptomatic patients. Levels of these biomarkers are frequently chronically elevated in asymptomatic patients with ESRD who are receiving maintenance dialysis. Other imaging biomarkers commonly encountered in nephrologists' clinical practice, such as coronary artery calcium measured by computed tomography, left ventricular hypertrophy, and carotid intima-media thickness, are also frequently abnormal in asymptomatic patients with ESRD. This article critically reviews the limited observational data on associations between cTnT, BNP, NT-pro-BNP, coronary artery calcium, left ventricular hypertrophy, and carotid intima-media thickness with cardiovascular events and death in non-dialysis-dependent patients with CKD. Although sufficient evidence suggests that these biomarkers may be used for prognostication, the diagnostic utility of cTnT, BNP, and NT-pro-BNP remain challenging in patients with CKD. Decreased renal clearance may affect the plasma levels of these biomarkers, and upper reference limits were originally derived in patients without CKD. Until better data are available, higher cutoffs, or a rise in level compared with previous values, have been proposed to help distinguish acute myocardial infarction from chronic elevations of cTnT in symptomatic patients with CKD. Additionally, it is not known whether these biomarkers are modifiable and amenable to interventions that could change hard clinical outcomes in patients with CKD not yet undergoing long-term dialysis.

Keywords: cardiovascular disease; chronic kidney disease; clinical epidemiology; coronary calcification.

Figure 1.

Cardiac troponins in patients with CKD. In response to injury, including altered hemodynamics, inflammation, and endothelial dysfunction, cardiac myocytes release troponin T (cTnT) and troponin I (cTnI) into the circulation from the troponin I-troponin T-troponin C (troponin I-T-C) complex present on the thin filament of the contractile apparatus. Serum cTnI and cTnT levels are measured by electrochemiluminescence immunoassay (ECLIA). Compared with cTnI, cTnT assays are standardized. In addition, several reasons explain why serum cTnT, compared with cTnI levels, are elevated in asymptomatic patients with ESRD. In asymptomatic patients with CKD, cardiac troponin levels are associated with various surrogate and hard clinical outcomes.

Figure 2.

Brain natriuretic peptides in patients with CKD. In response to increased stretch or tension, left ventricular myocytes release brain natriuretic peptide (BNP) and N-terminal-pro-BNP (NT-pro-BNP) from precursors. BNP is an active molecule with a short plasma half-life and is degraded in the circulation by enzymatic action. NT-pro-BNP is the inactive form of BNP, with a longer half-life. It is primarily cleared by the kidneys. Reduced eGFR correlates to a greater extent with elevated plasma NT-pro-BNP than to BNP levels. Increased NT-pro-BNP/BNP ratio correlates with advancing CKD stages, especially if the eGFR is <30 ml/min per 1.73 m². However, both BNP and NT-pro-BNP are associated with surrogate and hard clinical outcomes in asymptomatic patients with CKD.

Figure 3.

Utility of cardiac biomarkers in patients with CKD. Ideally, cardiac biomarkers should be useful in diagnosing atherosclerotic cardiovascular disease (ASCVD), risk-stratifying patients according to disease severity, monitoring ASCVD progression, identifying patients who may benefit from early intervention, and/or monitoring response to such interventions. The potential utility of circulating and imaging cardiac biomarkers in patients with CKD is similar. It includes one or many of the features of an ideal biomarker in relation with ASCVD.