Neutrophil Gelatinase-Associated Lipocalin Combined With Delta Serum Creatinine Provides Early Risk Stratification for Adverse Outcomes After Cardiac Surgery: A Prospective Observational Study

Objectives: Novel biomarkers of renal injury appear inconsistent in identifying a creatinine-based diagnosis of acute kidney injury. To be clinically useful, novel acute kidney injury biomarkers should identify patients at increased risk for adverse outcomes that are a consequence of acute kidney injury earlier and with greater utility than conventional creatinine-based metrics. We sought to determine the prognostic utility of both urinary neutrophil gelatinase-associated lipocalin and varying creatinine-based metrics of renal injury at multiple time points associated with cardiac surgery. Design: Prospective observational study. Setting: Academic medical center. Patients: Six hundred three adults undergoing cardiac surgery. Interventions: Nil. Measurements and Main Results: Urinary neutrophil gelatinase-associated lipocalin was measured at baseline and again less than 1 hour, 3 hours, and 18-24 hours after separation from cardiopulmonary bypass. Creatinine-based metrics included a Kidney Disease: Improving Global Outcomes definition of acute kidney injury through 7 days postoperatively as well as Delta SCr-initial, defined as the incremental change in S-Cr from baseline to first postoperative measure. Multivariable regression determined the prognostic utility of neutrophil gelatinase-associated lipocalin and creatinine, alone and in combination, for the primary composite outcome of hospital mortality or renal replacement therapy. The primary outcome occurred in 25 patients. Adjusted for covariates Delta SCr-initial greater than or equal to 0.0 mg/dL provided early prognostic utility for the primary outcome (odds ratio, 8.9; 95% CI, 3.0-26.6), the odds ratio comparable to a creatinine-based Kidney Disease: Improving Global Outcomes definition of acute kidney injury applied over 7 days postoperatively. The upper quartile of urinary neutrophil gelatinase-associated lipocalin best predicted the primary outcome when measured 18-24 hours post-cardiopulmonary bypass (odds ratio, 18.6; 95% CI, 5.1-68.4; p = 0.001) with earlier post-cardiopulmonary bypass measures of uncertain utility. Combining both Delta SCr-initial and neutrophil gelatinase-associated lipocalin measured 3 hours after cardiopulmonary bypass provided excellent early risk stratification for the primary outcome (odds ratio, 18.3; 95% CI, 4.5-75.0). Conclusions: Combining urinary neutrophil gelatinase-associated lipocalin with a novel creatinine-based metric, both available soon after completion of surgery, may provide previously unavailable early and effective risk stratification for serious adverse outcomes after cardiac surgery.