Clinical implication of plasma neutrophil gelatinase-associated lipocalin (NGAL) concentrations in patients with advanced carotid atherosclerosis

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is well established as an early and specific biomarker of kidney disease. Recent evidence further suggests that NGAL may play a crucial role in vascular remodeling and plaque instability during the development of atherosclerosis. METHODS: Plasma NGAL concentrations measured using a solid-phase enzyme-linked immunosorbent assay (ELISA) were correlated with medical history, risk factors and medication intake in 141 patients with advanced carotid atherosclerotic lesions who underwent carotid endarterectomy for vascular repair. RESULTS: Plasma NGAL concentrations were associated with patient age (R(s)=0.2055, p=0.0144), plasma homocysteine (R(s)=0.4274, p<0.00001) and serum creatinine (R(s)=0.4640, p<0.00001) concentrations and estimated glomerular filtration rate (eGFR) (R(s)=-0.4911, p<0.00001). Hypertensive patients, as well as those receiving therapy with angiotensin converting enzyme (ACE) inhibitors, presented with significantly enhanced plasma NGAL concentrations when compared to normotensive (p=0.0341) patients and those not treated (p=0.0004). Enhanced NGAL concentrations did not meet statistical significance for patients with advanced stenosis grade (p=0.0971) or a history of peripheral artery disease (p=0.0827). Multiple regression analysis identified homocysteine, creatinine, eGFR and treatment with ACE inhibitors (p=0.0019, <0.00001, 0.0005 and 0.0219, respectively) as independent predictors of NGAL concentration. CONCLUSIONS: Plasma NGAL concentrations were associated with patient age, hypertension, eGFR, creatinine and homocysteine concentrations and therapy with ACE inhibitors. The role of NGAL in the development of atherosclerosis needs to be further explored taking into consideration the uncontrolled effect of renal disease in atherosclerotic patients with multiple risk factors.