Neutrophil Gelatinase-Associated Lipocalin and Acute Kidney Injury after Cardiac Surgery: The Effect of Baseline Renal Function on Diagnostic Performance

Background and objectives: Neutrophil Gelatinase-Associated Lipocalin (NGAL) is rapidly released by renal tubules after injury, potentially allowing early identification of acute kidney injury (AKI) after cardiac surgery. However, the diagnostic performance of NGAL has varied widely in clinical studies, and it remains unknown what factors modify the relationship between NGAL and AKI. We hypothesized the relationship between urinary NGAL and AKI would vary with baseline renal function, allowing a stratified analysis to improve diagnostic performance of this novel biomarker.Design, setting, participants, & measurements: We performed a prospective observational study in 426 adult cardiac surgical patients. Urinary NGAL was serially determined, commencing preoperatively and continuing 24 hours postoperatively. AKI was defined as increase in serum creatinine from baseline by either >50% or >0.3 mg/dl within 48 hours postoperatively. Patients were stratified by baseline estimated GFR (eGFR). NGAL levels were compared between patients with and without AKI and diagnostic characteristics determined according to baseline eGFR.Results: In patients with baseline eGFR ≥60 ml/min, urinary NGAL was higher at all postoperative time points in patients who developed AKI compared with those who did not. In patients with baseline eGFR <60 ml/min, urinary NGAL did not differ at any time between those who did and those who did not develop AKI. Postoperative NGAL best identified AKI in patients with baseline eGFR 90 to 120 ml/min.Conclusions: The relationship between urinary NGAL and AKI after cardiac surgery varies with baseline renal function, with optimal discriminatory performance in patients with normal preoperative function.Acute Kidney Injury (AKI) is a common complication after cardiac surgery, with reported incidence varying from 20% to 50% depending on the definition used (1–4). Early detection of injury is desirable to facilitate early intervention aimed at limiting associated morbidity and mortality. Neutrophil Gelatinase-Associated Lipocalin (NGAL) is rapidly released by renal tubules in response to injury, and an acute rise in urinary NGAL has been reported to accurately identify evolving AKI in both pediatric and adult populations within 2 to 8 hours of cardiac surgery (5–9). However, other studies have found urinary NGAL to have only modest discriminant ability for AKI after cardiac surgery (3,10). Studies reporting excellent discriminant ability have generally excluded patients with preoperative renal dysfunction, whereas those studies reporting a more modest performance have included patients with a heterogeneous mix of baseline renal function. Although it is unknown whether baseline renal function modifies the relationship between NGAL and AKI, the existence of such a relationship may contribute to the limited predictive ability in these studies. Although NGAL is proposed as a real-time marker of acute renal injury rather than renal function, the nonlinear relationship between GFR and serum creatinine may mean that a relatively larger injury, producing a larger reduction in GFR, is required to cause a rise in serum creatinine sufficient to meet diagnostic criteria for AKI in a patient with normal baseline GFR. Conversely, a much smaller injury (and smaller incremental reduction in GFR) may be sufficient to cause a rise in creatinine that would diagnose AKI in a patient with impaired GFR at baseline. If true, the diagnostic utility of urinary NGAL for a creatinine-based diagnosis of AKI may be enhanced using an approach stratified by baseline renal function. We have previously reported a modest performance of urinary NGAL for early identification of evolving AKI in a large, unselected adult population undergoing cardiac surgery, with a wide range of baseline renal function. In this posthoc analysis we sought to investigate this potential source of effect modification to the relationship between NGAL and postoperative AKI. We hypothesized that the relationship between postoperative urinary NGAL and AKI would vary with baseline renal function, measured by estimated GFR (eGFR). We further hypothesized that the diagnostic performance of NGAL for postoperative AKI would be improved using an analysis stratified by baseline function, allowing the use of different diagnostic thresholds.