Jared J Cummings1, Andrew D Shaw1, Jing Shi2, Marcos G Lopez3, Jason B O'Neal1, Frederic T Billings4. 1. Division of Cardiothoracic Anesthesiology, Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tenn. 2. Department of Statistics, Walker Bioscience, Carlsbad, Calif. 3. Division of Critical Care Medicine, Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tenn. 4. Division of Cardiothoracic Anesthesiology, Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tenn; Division of Critical Care Medicine, Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tenn. Electronic address: frederic.t.billings@vanderbilt.edu.
Abstract
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 AKIin 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.
RCT Entities:
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.
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