Plasma Neutrophil Gelatinase-Associated Lipocalin Associates with New-Onset Chronic Kidney Disease in the General Population

Abstract

Circulating levels of neutrophil gelatinase-associated lipocalin (NGAL) have been associated with acute kidney injury and the severity and progression of chronic kidney disease (CKD). This study investigated its potential utility as a biomarker for the risk of new-onset CKD in a population-based cohort study. Individuals without CKD at baseline (n = 4660) who participated in the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) prospective population-based cohort study in the Netherlands were included. Baseline plasma NGAL concentrations were investigated for their associations with new-onset CKD, defined as a composite outcome of an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, urinary albumin excretion (UAE) > 30 mg/24-h, or both. Mean (±SD) plasma NGAL concentrations were 104.0 (±34.7) μg/L and median eGFR was 96 [IQR: 85.3–105.8] mL/min/1.73 m2. After median follow-up of 8.3 [IQR: 7.8–8.9] years, 467 participants developed new-onset CKD. Plasma NGAL concentrations were significantly associated with an increased risk of new-onset CKD (hazard ratio [HR] per doubling 1.35 [95% CI: 1.11–1.63], p = 0.002), even after adjustment for potentially confounding factors (1.37 [1.09–1.73], p = 0.007) except baseline eGFR (1.09 [0.86–1.37], p = 0.490). In secondary analyses, plasma NGAL concentrations were significantly associated with new-onset CKD as defined by eGFR < 60 mL/min/1.73 m2 alone (adjusted HR per doubling 2.54 [1.69–3.80], p < 0.001), which was abrogated after adjustment for eGFR (1.05 [0.69–1.59], p = 0.828), also when UAE > 30 mg/24-h was set as individual outcome (1.05 [0.82–1.35], p = 0.705). Higher plasma NGAL concentrations are associated with an increased risk of developing CKD in the general population. This association is dependent on renal function, and mainly driven by new-onset CKD as defined by renal function decline.