Prediction of cardiac surgery associated acute kidney injury using response to loop diuretic and urine neutrophil gelatinase associated lipocalin

Abstract

Abstract Background Cardiac surgery associated acute kidney injury (CS-AKI) is common. Urine response to loop diuretic and urine neutrophil gelatinase associated lipocalin (uNGAL) are separately associated with CS-AKI. We aimed to determine whether urine response to loop diuretic and uNGAL together were associated with postoperative day 2–4 CS-AKI. Methods Two-center prospective observational study (ages 0–18 years). uNGAL (8–12 h after admission) (ng/mL) and urine response to loop diuretic (6 h for bolus furosemide and 12 h for infusion bumetanide) (mL/kg/hr) were measured. All diuretic doses were converted to furosemide equivalents. The primary outcome was day 2–4 CS-AKI. Patients were sub-phenotyped using a priori cutoffs (uNGAL +  ≥ 100 ng/mL and UOP +  < 1.5 mL/kg/hr) and optimal cutoffs (uNGAL +  ≥ 127 ng/mL and UOP +  ≤ 0.79 mL/kg/hr): 1) uNGAL–/UOP–, 2) uNGAL–/UOP + , 3) uNGAL + /UOP–, and 4) uNGAL + /UOP + . Multivariable regression was used to assess the association of uNGAL, UOP and each sub-phenotype with outcomes. Results 476 patients were included. CS-AKI occurred in 52 (10.9%). uNGAL was associated with 2.59-fold greater odds (95%CI: 1.52–4.41) of CS-AKI. UOP was not associated with CS-AKI. Compared with uNGAL + alone, uNGAL + /UOP + improved prediction of CS-AKI using a priori and optimal cutoffs respectively (AUC 0.70 vs. 0.75). Both uNGAL + /UOP + (IQR OR:4.63, 95%CI: 1.74–12.32) and uNGAL + /UOP– (IQR OR:5.94, 95%CI: 2.09–16.84) were associated with CS-AKI when compared with uNGAL–/UOP–. Conclusions uNGAL is associated with CS-AKI. The sub-phenotype association was largely driven by uNGAL. Future studies standardizing diuretic dose and timing may be needed to refine the combined performance for clinical decision making. Graphical abstract