Plasma Neutrophil Gelatinase-Associated Lipocalin Reflects Both Inflammation and Kidney Function in Patients with Myocardial Infarction

Abstract

Background/Aims: Neutrophil gelatinase-associated lipocalin (NGAL) has emerged as a marker for acute kidney injury and cardiovascular outcome. However, the relative importance of inflammation versus kidney function on plasma NGAL levels is uncertain, making the interpretation of plasma NGAL unclear. Accordingly, we investigated the relationship between plasma NGAL, inflammation and kidney function in patients with myocardial infarction (MI). Methods: We prospectively included 584 patients with acute ST-segment elevation MI (STEMI) treated with primary percutaneous coronary intervention (PCI) from 2006 to 2008. Blood samples were drawn immediately before PCI. Additionally, we included 42 patients who had 4 blood samples drawn before and after PCI. Plasma NGAL was measured using a time-resolved immunofluorometric assay. Cross-sectional analyses were performed in these two single-center, prospective study cohorts. Results: Estimated glomerular filtration rate (eGFR) was associated significantly more strongly with plasma NGAL when eGFR was abnormal compared to normal eGFR: a decrease in eGFR of 10 ml/min was associated with an increase in NGAL of 27% (18-36%) versus 4% (1-7%), respectively (p < 0.001). Leukocyte count and C-reactive protein were the main determinants of plasma NGAL in patients with normal eGFR, whereas eGFR was the main determinant at reduced kidney function. Conclusions: eGFR determines the association of NGAL with either inflammation or kidney function; in patients with normal eGFR, plasma NGAL reflects inflammation but when eGFR is reduced, plasma NGAL reflects kidney function, highlighting the dual perception of plasma NGAL. From a clinical perspective, eGFR may be used to guide the interpretation of elevated NGAL levels in patients with STEMI.

Elevated Neutrophil Gelatinase-Associated Lipocalin for the Assessment of Structural versus Functional Renal Damage among ST-Segment Elevation Myocardial Infarction Patients

“…Elevated CRP level was also shown to be associated with higher risk for AKI in patients undergoing emergent PCI [25]. The interaction between NGAL and CRP in STEMI patients was previously described by Lindberg et al [22]. In that report, the combination of high CRP/high NGAL significantly conferred the highest mortality, whereas low CRP/low NGAL conferred the lowest mortality.…”

“…Elevated NGAL levels were previously shown to be associated with adverse outcomes in STEMI patients [22,23]. The utilization of NGAL in those reports was mainly as a biomarker of an inflammatory response and patient population included patients with CKD and cardiogenic shock, both known to be associated with increased NGAL expression due chronic renal damage [14] or severe inflammatory response [15] and thus may not truly reflect acute tubular damage.…”

Plasma neutrophil gelatinase-associated lipocalin levels are associated with the presence and severity of coronary heart disease

“…In previous studies, which evaluated renal dysfunction and heart failure, CAG and percutaneous coronary intervention (PCI) were associated with increased plasma NGAL levels [16, 17]. Some studies have shown high plasma NGAL levels independently predicts all-cause mortality in STEMI patients treated with PCI independent of eGFR[18, 19], but recent research indicates that plasma NGAL levels do not predict mortality and cardiovascular disease risk independent of renal function and eGFR was the main determinant of plasma NGAL in patients with reduced eGFR (<60 ml/min) [20–22]. Thus, eligible patients included in this study did not have kidney disease or heart failure.…”

More than a simple biomarker: the role of NGAL in cardiovascular and renal diseases

“…In heart failure and various other inflammatory pathologies, serum or plasma levels of NGAL have been shown to correlate with those of other inflammatory markers such as TNF-, CRP, IL-6 or leukocytes number (101,102). and MCP-1 (5).…”