Postoperative biomarkers predict acute kidney injury and poor outcomes after adult cardiac surgery

Abstract

Acute kidney injury (AKI) is a frequent complication of cardiac surgery and increases morbidity and mortality. The identification of reliable biomarkers that allow earlier diagnosis of AKI in the postoperative period may increase the success of therapeutic interventions. Here, we conducted a prospective, multicenter cohort study involving 1219 adults undergoing cardiac surgery to evaluate whether early postoperative measures of urine IL-18, urine neutrophil gelatinase-associated lipocalin (NGAL), or plasma NGAL could identify which patients would develop AKI and other adverse patient outcomes. Urine IL-18 and urine and plasma NGAL levels peaked within 6 hours after surgery. After multivariable adjustment, the highest quintiles of urine IL-18 and plasma NGAL associated with 6.8-fold and 5-fold higher odds of AKI, respectively, compared with the lowest quintiles. Elevated urine IL-18 and urine and plasma NGAL levels associated with longer length of hospital stay, longer intensive care unit stay, and higher risk for dialysis or death. The clinical prediction model for AKI had an area under the receiver-operating characteristic curve (AUC) of 0.69. Urine IL-18 and plasma NGAL significantly improved the AUC to 0.76 and 0.75, respectively. Urine IL-18 and plasma NGAL significantly improved risk prediction over the clinical models alone as measured by net reclassification improvement (NRI) and integrated discrimination improvement (IDI). In conclusion, urine IL-18, urine NGAL, and plasma NGAL associate with subsequent AKI and poor outcomes among adults undergoing cardiac surgery.

Trial registration: ClinicalTrials.gov NCT00774137.

Figure 1.

Flow of study population.

Figure 2.

Urine IL-18, urine NGAL, and plasma NGAL peaked within 6 hours after surgery. Yellow bar indicates the IQR of the day to the first evidence of AKI in patients with AKI. Blue and green bars represent the IQR (25th to 75th percentiles) for AKI and non-AKI patients, respectively. The solid lines denote the median values. AKI was defined by receipt of acute dialysis or a doubling in serum creatinine during the hospital stay. Day 1 is the day of surgery, with time 0 representing the point when the patient arrived in the postoperative ICU.

Figure 3.

Quintiles of urine IL-18, urine NGAL, and plasma NGAL had a graded relationship with the risk for AKI. Unadjusted P for trend is reported. Risk of AKI (%) is the percentage of AKI patients within each quintile. AKI was defined by receipt of acute dialysis or evidence of postoperative doubling of the preoperative serum creatinine value.

Figure 4.

Diagnostic performance of the first postoperative value of urine IL-18, urine NGAL, and plasma NGAL for the detection of AKI. Receiver-operating characteristic (ROC) curves show the diagnostic performance of the four biomarkers and the table shows the performance of each biomarker at the fifth quintile.