Urine neutrophil gelatinase-associated lipocalin levels do not improve risk prediction of progressive chronic kidney disease

Abstract

Novel biomarkers may improve our ability to predict which patients with chronic kidney disease (CKD) are at higher risk for progressive loss of renal function. Here we assessed the performance of urine neutrophil gelatinase-associated lipocalin (NGAL) for outcome prediction in a diverse cohort of 3386 patients with CKD in the CRIC study. In this cohort, the baseline mean estimated glomerular filtration rate (eGFR) was 42.4 ml/min/1.73m ²; the median 24-hour urine protein was 0.2 gm/day; and the median urine NGAL concentration was 17.2 ng/mL. Over an average follow-up of 3.2 years, there were 689 cases in which the eGFR was decreased by half or incident end-stage renal disease developed. Even after accounting for eGFR, proteinuria and other known CKD progression risk factors, urine NGAL remained a significant independent risk factor (Cox model hazard ratio 1.70 highest to lowest quartile). The association between baseline urine NGAL levels and risk of CKD progression was strongest in the first two years of biomarker measurement. Within this time frame, adding urine NGAL to a model which included eGFR, proteinuria and other CKD progression risk factors led to net reclassification improvement of 24.7%; but the C-statistic remained nearly identical. Thus, while urine NGAL was an independent risk factor of progression among patients with established CKD of diverse etiology, it did not substantially improve prediction of outcome events.