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

J Thorac Cardiovasc Surg. 2019 Apr;157(4):1545-1553.e5. doi: 10.1016/j.jtcvs.2018.08.090. Epub 2018 Sep 26.

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 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.

Keywords: IGFBP7; NephroCheck, prediction; TIMP-2; acute kidney injury; biomarker; cardiac surgery.

Publication types

  • Comparative Study
  • Video-Audio Media

MeSH terms

  • Acute Kidney Injury / diagnosis
  • Acute Kidney Injury / etiology*
  • Acute Kidney Injury / urine
  • Aged
  • Biomarkers / urine
  • Cardiac Surgical Procedures / adverse effects*
  • Cell Cycle Checkpoints*
  • Female
  • Humans
  • Insulin-Like Growth Factor Binding Proteins / urine*
  • Intraoperative Period
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prospective Studies
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Tissue Inhibitor of Metalloproteinase-2 / urine*
  • Treatment Outcome
  • Up-Regulation
  • Urinalysis

Substances

  • Biomarkers
  • Insulin-Like Growth Factor Binding Proteins
  • TIMP2 protein, human
  • insulin-like growth factor binding protein-related protein 1
  • Tissue Inhibitor of Metalloproteinase-2