Objective: Tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factorbinding protein 7 (IGFBP7) are postoperative urinary biomarkers of renal stress and AKI. We conducted this study to test the hypothesis that intraoperative concentrations of urinary [TIMP-2]•[IGFBP7] are associated with postoperative AKI. Methods: We measured urinary [TIMP-2]•[IGFBP7] at eight perioperative timepoints in 400 patients who participated in a RCT of statins for AKI in cardiac surgery. We compared [TIMP-2]•[IGFBP7] between subjects who did and did not develop KDIGO stage 2-3 AKI within 48 hours of surgery, adjusted for AKI risk factors. Results: Fourteen patients (3.5%) met the primary endpoint of stage 2-3 AKI within 48 hours of surgery, and an additional 77 patients (19.3%) developed stage 1 AKI. Patients who developed stage 2-3 AKI displayed bimodal elevations of [TIMP-2]•[IGFBP7], with a first elevation (median 0.45 [ng/mL] 2 /1000) intraoperatively and the second peak (1.45 [ng/mL] 2 /1000) six hours postoperatively. Patients who did not develop AKI did not have any elevations in [TIMP-2]•[IGFBP7]. Each 10-fold increase in intraoperative [TIMP-2]•[IGFBP7] was independently associated with a 290% increase in the odds of stage 2-3 AKI (P=0.01), and each 10-fold increase in six hours postoperative [TIMP-2]•[IGFBP7] a 650% increase (P<0.001). The maximum [TIMP-2]•[IGFBP7] between these two timepoints provided an AUROC of 0.82 (95% CI: 0.73-0.90), 100% sensitivity, and 100% negative predictive value using the >0.3 cutoff to predict stage 2-3 AKI.
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