Temporal Relationship and Predictive Value of Urinary Acute Kidney Injury Biomarkers After Pediatric Cardiopulmonary Bypass

The Heart Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Journal of the American College of Cardiology (Impact Factor: 16.5). 11/2011; 58(22):2301-9. DOI: 10.1016/j.jacc.2011.08.017
Source: PubMed


We investigated the temporal pattern and predictive value (alone and in combination) of 4 urinary biomarkers (neutrophil gelatinase-associated lipocalin [NGAL], interleukin [IL]-18, liver fatty acid-binding protein [L-FABP], and kidney injury molecule [KIM]-1) for cardiac surgery-associated acute kidney injury (AKI).
Serum creatinine (S(Cr)) is a delayed marker for AKI after cardiopulmonary bypass (CPB). Rapidly detectable AKI biomarkers could allow early intervention and improve outcomes.
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 S(Cr) from baseline within 48 h 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 area under the curve (AUC), net reclassification improvement, and integrated discrimination improvement.
AKI occurred in 27% of patients. Urine NGAL significantly increased in AKI patients at 2 h after CPB initiation. IL-18 and L-FABP increased at 6 h, and KIM-1 increased at 12 h. Biomarker elevations were correlated with AKI severity and clinical outcomes and improved AKI prediction above a clinical model. At 2 h, addition of NGAL increased the AUC from 0.74 to 0.85 (p < 0.0001). At 6 h, 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 net reclassification improvement and integrated discrimination improvement. Biomarker combinations further improved AKI prediction.
Urine NGAL, IL-18, L-FABP, and KIM-1 are sequential predictive biomarkers for AKI and are correlated 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.

  • Source
    • "It is therefore expected to increase in dogs with heatstroke , which invariably have severe kidney tubular injury (Bruchim et al., 2009). In humans, NGAL is induced as early as 2 h following kidney injury, and it is also extremely sensitive for detecting AKI in dogs at risk, early in the course of disease (Mishra et al., 2003; Krawczeski et al., 2011). Confirming the results of previous canine studies, UNGAL was increased in all dogs with heatstroke, further indicating that dogs with heatstroke have already sustained kidney injury at presentation, even though sCr was within reference intervals in some. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Heatstroke is often associated with acute kidney injury (AKI). The objectives of this study were to characterize the kidney damage occurring in canine heatstroke using routine and novel biomarkers and to assess their diagnostic and prognostic performance. Thirty dogs with naturally occurring heatstroke were enrolled prospectively. Blood and urine specimens were collected at presentation, at 4 h post-presentation and every 12 h until discharge or death. The glomerular filtration rate (GFR) and electrolyte fractional excretion (FE) at 4 h post-presentation were also calculated, based on urinary clearances. AKI was further characterized by evaluating urine neutrophil gelatinase-associated lipocalin/creatinine ratio (UNGAL), urine retinol-binding protein/creatinine ratio (URBP), urine C-reactive protein/creatinine ratio (UCRP) and urine protein to creatinine ratio (UPC). These biomarkers were compared to those for 13 healthy dogs. Thirteen dogs (43%) died and 17 (57%) survived. Median serum creatinine concentration at presentation was 1.69 mg/dL (range, 0.5-4.7 mg/dL), while concurrent GFR was markedly decreased (median 0.60 mL/min/kg; range, 0.00-3.10 mL/min/kg). Median Na fractional excretion was 0.08 (range, 0.01-0.41) and was an accurate predictor of AKI (area under curve 0.89; 95% confidence intervals 0.76-1.00). Median UPC at presentation was 4.8 (range, 0.4-46.0). Median UCRP, URBP and UNGAL were increased in all dogs with heatstroke, and were mean 232, 133, and 1213-fold higher than healthy control dogs, respectively. In conclusion, although AKI occurs invariably in dogs with heatstroke, it is often subclinical at presentation. Damage occurs in both the renal tubules and the glomeruli. Novel kidney function tests for the characterization of renal injury and its severity are superior to conventional markers and could be used to facilitate early diagnosis of AKI.
    Full-text · Article · Sep 2015 · The Veterinary Journal
  • Source
    • "Although plasma NGAL was increased in AKI patients in this study, neither increased levels of plasma or urinary NGAL were reliable predictors of AKI post cardiac surgery. Several other studies reporting increased NGAL as a sensitive and specific predictor of AKI after cardiac surgery have used urinary NGAL and described paediatric populations (Bennett et al., 2008; Krawczeski et al., 2011; Mishra et al., 2005). In the adult cardiac surgery population, several authors, in line with our findings, have reported NGAL as a postoperative marker with variable performance in the prediction of AKI (Liangos et al., 2009; Peco-Antic et al., 2013; Sargentini et al., 2012; Wagener et al., 2008). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Context: Cardiac surgery. Objective: To compare plasma and urinary neutrophil gelatinase-associated lipocalin (P-/U-NGAL) in on-pump (n = 43) versus off-pump (n = 40) surgery. Materials and methods: We obtained perioperative P-/U-NGAL and outcome data. Results: P-/U-NGAL increased after surgery. P-NGAL was higher post-surgery in on pump patients (139 versus 67 µg L(-1); p < 0.001), but not at 24 h. There were no differences in U-NGAL. Correlation between P-/U-NGAL and plasma creatinine was weak. Discussion: P-NGAL acts like a neutrophil activation biomarker and U-NGAL like a tubular injury marker. Conclusion: On-pump patients had greater neutrophil activation. On- versus off-pump surgery had similar impact on tubular cells.
    Full-text · Article · Feb 2014 · Biomarkers
  • Source
    • "Finally, our AKI definition has significant shortcomings. It did not include urine output as intraoperative ultrafiltration and early postoperative diuretics could have influenced it [21]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Acute kidney injury (AKI) is significant problem in children undergoing cardiopulmonary bypass (CPB). The aims of this study were to assess the diagnostic validity of serum CysC (sCysC), serum (sNGAL) and urine neutrophil gelatinase lipocalin (uNGAL), urine kidney injury molecule (uKIM)-1, and urine liver fatty acid-binding protein (uL-FABP) to predict AKI presence and severity in children undergoing CPB. We performed a prospective single-center evaluation of sCysC, sNGAL, uNGAL, uKIM-1 and uL-FABP at 0, 2, 6, 24 and 48 hours postoperatively in children undergoing CBP during cardiac surgery. AKI was defined as≥25% decrease in the estimated creatinine clearance (eCCl) from pre-operative baseline at 48h after surgery. Of the 112 patients, 18 patients (16.1 %) developed AKI; four of them needed acute dialysis treatment and three AKI patients died. In AKI compared to no AKI group, sCysC at 2 h, uNGAL and uL-FABP at 2-48 h were significantly increased, as well as CPB, aortic cross clamp time and length of hospital stay. Biomarkers increased with worsening AKI severity. At 2 h after CPB the best accuracy for diagnosis of AKI had uL-FABP and sCysC with area under the receiver operator curve (AUC) of 0.89 and 0.73, respectively. At 6 and 24 h after CPB the best AUC was found for uL-FABP (0.75 and 0.87 respectively) and for uNGAL (0.70 and 0.93, respectively). sCysC, uNGAL and uL- FABP are reliable early predictors for AKI after CBP. By allowing earlier timing of injury, and earlier intervention they could improve AKI outcome.
    Full-text · Article · Jul 2013 · Clinical biochemistry
Show more