Objectives We investigated the temporal pattern and predictive value (alone and in combination) of four urinary biomarkers [neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), liver fatty-acid binding protein (L-FABP) and kidney injury molecule-1 (KIM-1)] for cardiac surgery-associated acute kidney injury (AKI). Background Serum creatinine (SCr) is a delayed marker for AKI after cardiopulmonary bypass (CPB). Rapidly detectable AKI biomarkers could allow early intervention and improve outcomes. Methods Data from 220 pediatric patients were analyzed. Urine samples were obtained before and at intervals after CPB initiation. AKI was defined as a ≥50% increase in SCr from baseline within 48h after CPB. The temporal pattern of biomarker elevation was established and biomarker elevations were correlated with AKI severity and clinical outcomes. Biomarker predictive abilities were evaluated by AUC, net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Results AKI occurred in 27% of patients. Urine NGAL significantly increased in AKI patients at 2h after CPB initiation. IL-18 and L-FABP increased at 6h and KIM-1 increased at 12h. Biomarker elevations correlated with AKI severity and clinical outcomes, and improved AKI prediction above a clinical model. At 2h, addition of NGAL increased the AUC from 0.74 to 0.85 (p<0.0001). At 6h, NGAL, IL-18 and L-FABP each improved the AUC from 0.72 to 0.91, 0.84 and 0.77, respectively (all p<0.05). The added predictive ability of the biomarkers was supported by NRI and IDI. Biomarker combinations further improved AKI prediction. Conclusion Urine NGAL, IL-18, L-FABP, and KIM-1 are sequential predictive biomarkers for AKI and correlate with disease severity and clinical outcomes after pediatric CPB. These biomarkers, particularly in combination, may help establish the timing of injury and allow earlier intervention in AKI.

No abstract

Background Idiopathic nephrotic syndrome (NS) is the most common glomerular disorder of childhood. Invasive biopsy remains the diagnostic method of choice for NS. Prognosis correlates with steroid responsiveness, from sensitive (SSNS) to resistant (SRNS). Neutrophil gelatinase-associated lipocalin (NGAL) has been demonstrated to be a powerful risk marker of chronic kidney disease progression. We set out to determine if urine NGAL can distinguish between patients with SRNS, SSNS, and healthy controls. Methods Urine and clinical data were collected from patients at Cincinnati Children's Hospital who were recently diagnosed with active nephrotic syndrome as well as healthy controls. Participants included SRNS (n=15), SSNS (n=14), and healthy controls (n=10). Urinary NGAL was measured by ELISA and normalized to creatinine. Results Median NGAL was significantly (p <0.001) higher in SRNS (172.3 ng/ml, IQR 18.8–789) than both SSNS (6.3 ng/ml, IQR 4.9–9.9) and healthy controls (6.5 ng/ml, IQR 4.2–9.1). The area under the curve (AUC) for NGAL to distinguish SRNS from SSNS was 0.91 (p<0.0001). NGAL levels demonstrated a significant negative correlation with glomerular filtration rate (r=−0.5, p<0.001). Results did not change with NGAL corrected for urine creatinine and were independent of the degree of proteinuria. Conclusions NGAL levels differentiate SSNS from SRNS and correlate with disease severity in SRNS.