Urinary neutrophil gelatinase-associated lipocalin as a predictor of cardiovascular events in patients with chronic kidney disease

Abstract

Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular (CV) events. Recently, elevated neutrophil gelatinase-associated lipocalin (NGAL) levels have been reported in patients with heart failure, coronary heart disease, or stroke. Our aim was to assess urinary NGAL as a predictor of CV events in patients with CKD. This was a prospective observational cohort study of 404 patients with predialysis CKD. CV events were defined as CV death, acute coronary syndrome, hospitalization for worsening heart failure, stroke and dissection of aorta. During a mean follow-up period of 33 months, 77 CV events (19.1 %) occurred. After adjustment for gender, age, diabetes, previous cardiovascular disease, urinary albumin/creatinine ratio (UACR), estimated glomerular filtration rate, hemoglobin, and high-sensitivity C-reactive protein, patients with the other quartiles of urinary NGAL had significantly higher risk of CV events compared with patients with the lowest quartile (hazard ratio (HR) 2.81, 95 % confidence interval (CI) 1.01-7.81, P = 0.047 for Q2, HR 3.31, 95 % CI 1.22-9.00, P = 0.019 for Q3, and HR 3.27, 95 % CI 1.15-9.29, P = 0.026 for Q4). Regarding the combination of urinary NGAL with UACR, we also stratified patients into four groups according to whether the level of each marker was above or below the median (61.8 μg per gram creatinine (gCr) for NGAL and 351.1 mg/gCr for UACR). Four-year CV event-free survival rates were 89.2, 79.6, 71.8, and 51.5 % in order for the four respective groups (P < 0.0001). Elevated urinary NGAL was able to predict future CV events in CKD patients, and had incremental predictive value with elevated UACR.