Urinary biomarkers TIMP-2 and IGFBP7 early predict acute kidney injury after major surgery

PLoS One. 2015 Mar 23;10(3):e0120863. doi: 10.1371/journal.pone.0120863. eCollection 2015.

Abstract

Objective: To assess the ability of the urinary biomarkers IGFBP7 (insulin-like growth factor-binding protein 7) and TIMP-2 (tissue inhibitor of metalloproteinase 2) to early predict acute kidney injury (AKI) in high-risk surgical patients.

Introduction: Postoperative AKI is associated with an increase in short and long-term mortality. Using IGFBP7 and TIMP-2 for early detection of cellular kidney injury, thus allowing the early initiation of renal protection measures, may represent a new concept of evaluating renal function.

Methods: In this prospective study, urinary [TIMP-2]×[IGFBP7] was measured in surgical patients at high risk for AKI. A predefined cut-off value of [TIMP-2]×[IGFBP7] >0.3 was used for assessing diagnostic accuracy. Perioperative characteristics were evaluated, and ROC analyses as well as logistic regression models of risk assessment were calculated with and without a [TIMP-2]×[IGFBP7] test.

Results: 107 patients were included in the study, of whom 45 (42%) developed AKI. The highest median values of biomarker were detected in septic, transplant and patients after hepatic surgery (1.24 vs 0.45 vs 0.47 ng/l²/1000). The area under receiving operating characteristic curve (AUC) for the risk of any AKI was 0.85, for early use of RRT 0.83 and for 28-day mortality 0.77. In a multivariable model with established perioperative risk factors, the [TIMP-2]×[IGFBP7] test was the strongest predictor of AKI and significantly improved the risk assessment (p<0.001).

Conclusions: Urinary [TIMP-2]×[IGFBP7] test sufficiently detect patients with risk of AKI after major non-cardiac surgery. Due to its rapid responsiveness it extends the time frame for intervention to prevent development of AKI.

Publication types

  • Clinical Trial

MeSH terms

  • Acute Kidney Injury / diagnosis
  • Acute Kidney Injury / etiology
  • Acute Kidney Injury / pathology
  • Acute Kidney Injury / urine*
  • Biomarkers / urine
  • Cell Cycle Checkpoints
  • Female
  • Humans
  • Insulin-Like Growth Factor Binding Proteins / urine*
  • Kidney / pathology
  • Male
  • Middle Aged
  • Perioperative Period
  • Postoperative Complications / diagnosis
  • Postoperative Complications / etiology
  • Postoperative Complications / pathology
  • Postoperative Complications / urine*
  • ROC Curve
  • Risk Assessment
  • Time Factors
  • Tissue Inhibitor of Metalloproteinase-2 / urine*
  • 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

Grant support

The authors recieved no specific funding for this work.