(TIMP2) x (IGFBP7) as early renal biomarker for the prediction of acute kidney injury in aortic surgery (TIGER). A single center observational study

PLoS One. 2021 Jan 7;16(1):e0244658. doi: 10.1371/journal.pone.0244658. eCollection 2021.

Abstract

Objective: Postoperative acute kidney injury (po-AKI) is frequently observed after major vascular surgery and impacts on mortality rates. Early identification of po-AKI patients using the novel urinary biomarkers insulin-like growth factor-binding-protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) might help in early identification of individuals at risk of AKI and enable timely introduction of preventative or therapeutic interventions with the aim of reducing the incidence of po-AKI. We investigated whether biomarker-based monitoring would allow for early detection of po-AKI in patients undergoing abdominal aortic interventions.

Methods: In an investigator-initiated prospective single-center observational study in a tertiary care academic center, adult patients with emergency/ elective abdominal aortic repair were included. Patients were tested for concentrations of urinary (TIMP-2) x (IGFBP7) at baseline, after surgical interventions (PO), and in the mornings of the first postoperative day (POD1). The primary endpoint was a difference in urinary (TIMP-2) x (IGFBP7) levels at POD1 in patients with/ without po-AKI (all KDIGO stages, po-AKI until seven days after surgery). Secondary endpoints included sensitivity/ specificity analyses of previously proposed cut-off levels and clinical outcome measures (e.g. need for renal replacement therapy).

Results: 93 patients (n = 71 open surgery) were included. Po-AKI was observed in 33% (31/93) of patients. Urinary (TIMP-2) x (IGFBP7) levels at POD1 did not differ between patients with/ without AKI (median 0.39, interquartile range [IQR] 0.13-1.05 and median 0.23, IQR 0.14-0.53, p = .11, respectively) and PO (median 0.2, IQR 0.08-0.42, 0.18, IQR 0.09-0.46; p = .79). Higher median (TIMP-2) x (IGFBP7) levels were noted in KDIGO stage 3 pAKI patients at POD1 (3.75, IQR 1.97-6.92; p = .003). Previously proposed cutoff levels (0.3, 2) showed moderate sensitivity/ specificity (0.58/0.58 and 0.16/0.98, respectively).

Conclusion: In a prospective monocentric observational study in patients after abdominal aortic repair, early assessment of urinary (TIMP-2) x (IGFBP7) did not appear to have adequate sensitivity/ specificity to identify patients that later developed postoperative AKI.

Clinicaltrials.gov: NCT03469765, registered March 19, 2018.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / etiology*
  • Acute Kidney Injury / urine
  • Aged
  • Aged, 80 and over
  • Aorta / surgery*
  • Biomarkers / urine
  • Female
  • Humans
  • Insulin-Like Growth Factor Binding Proteins / urine*
  • Male
  • Middle Aged
  • Postoperative Complications / etiology
  • Postoperative Complications / urine
  • Prospective Studies
  • Risk Assessment
  • Sensitivity and Specificity
  • Tissue Inhibitor of Metalloproteinase-2 / urine*
  • Vascular Surgical Procedures / adverse effects*

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

Associated data

  • ClinicalTrials.gov/NCT03469765

Grants and funding

JW received a fund by a scientific research fund of the Department of Anes-thesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern (Grant Nr. WAJD-1-18). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. There was no additional external funding received for this study.