Intraoperative prediction of cardiac surgery-associated acute kidney injury using urinary biomarkers of cell cycle arrest

Objective: Tissue inhibitor of metalloproteinases 2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) are postoperative urinary biomarkers of renal stress and acute kidney injury (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 8 perioperative timepoints in 400 patients who participated in a randomized controlled trial of atorvastatin for AKI in cardiac surgery. We compared [TIMP-2].[IGFBP7] between subjects who did and did not develop KDIGO stage 2 or 3 AKI within 48 hours of surgery, adjusted for AKI risk factors. Results: Fourteen patients (3.5%) met the primary endpoint of stage 2 or 3 AKI within 48 hours of surgery, and an additional 77 patients (19.3%) developed stage 1 AKI. Patients who developed stage 2 or 3 AKI displayed bimodal elevations of [TIMP-2].[IGFBP7], with a first elevation (median, 0.45 [ng/mL](2)/1000) intraoperatively and a second elevation (1.45 [ng/mL] 2/1000) 6 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 or 3 AKI (P =.01), and each 10-fold increase in the 6 hours postoperative [TIMP-2].[IGFBP7] was independently associated with a 650% increase in the odds of stage 2 or 3 AKI (P<. 001). The maximum [TIMP-2].[IGFBP7] between these 2 timepoints provided an area under the receiver operating characteristic curve of 0.82 (95% confidence interval [CI], 0.73-0.90), 100% sensitivity, and 100% negative predictive value using the >0.3 cutoff to predict stage 2 or 3 AKI. Conclusions: Intraoperative elevations of [TIMP-2].[IGFBP7] can predict moderate or severe AKI and could provide an opportunity to alter postoperative management to prevent kidney injury.