Urinary Tissue Inhibitor of Metalloproteinase-2 and Insulin-Like Growth Factor-Binding Protein 7 for Risk Stratification of Acute Kidney Injury in Patients with Sepsis

Patrick M. Honore, H. Bryant Nguyen, Michelle Gong, Lakhmir S. Chawla, Sean M. Bagshaw, Antonio Artigas, Jing Shi, Olivier Joannes-Boyau, Jean Louis Vincent, John A. Kellum

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Objectives: To examine the performance of the urinary biomarker panel tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 in patients with sepsis at ICU admission. To investigate the effect of nonrenal organ dysfunction on tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 in this population. Method: In this ancillary analysis, we included patients with sepsis who were enrolled in either of two trials including 39 ICUs across Europe and North America. The primary endpoint was moderate-severe acute kidney injury (equivalent to Kidney Disease Improving Global Outcome stage 2-3) within 12 hours of enrollment. We assessed biomarker performance by calculating the area under the receiver operating characteristic curve, sensitivity, specificity, and negative and positive predictive values at three cutoffs: 0.3, 1.0, and 2.0 (ng/mL) 2 /1,000. We also calculated nonrenal Sequential Organ Failure Assessment scores for each patient on enrollment and compared tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 results in patients with and without acute kidney injury and across nonrenal Sequential Organ Failure Assessment scores. Finally, we constructed a clinical model for acute kidney injury in this population and compared the performance of the model with and without tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7. Results: We included 232 patients in the analysis and 40 (17%) developed acute kidney injury. We observed significantly higher urine tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 in patients with acute kidney injury than without acute kidney injury in both patients with low and high nonrenal Sequential Organ Failure Assessment scores (p < 0.001). The area under the receiver operating characteristic curve (95% CI) of tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 was 0.84 (0.73-0.92) and 0.85 (0.76-0.94), in low and high nonrenal Sequential Organ Failure Assessment score subgroups. Performance of the tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 test was not modified by nonrenal Sequential Organ Failure Assessment (p = 0.70). In multivariate analysis, the addition of tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 significantly improved the performance of a clinical model for predicting acute kidney injury (p = 0.015). Conclusion: Urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 accurately predicts acute kidney injury in septic patients with or without other organ failures.

Original languageEnglish (US)
Pages (from-to)1851-1860
Number of pages10
JournalCritical care medicine
Volume44
Issue number10
DOIs
StatePublished - Oct 1 2016

Keywords

  • acute kidney injury
  • insulin-like growth factor-binding protein 7
  • organ dysfunction
  • risk prediction
  • sepsis
  • tissue inhibitor of metalloproteinase-2

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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    Honore, P. M., Nguyen, H. B., Gong, M., Chawla, L. S., Bagshaw, S. M., Artigas, A., Shi, J., Joannes-Boyau, O., Vincent, J. L., & Kellum, J. A. (2016). Urinary Tissue Inhibitor of Metalloproteinase-2 and Insulin-Like Growth Factor-Binding Protein 7 for Risk Stratification of Acute Kidney Injury in Patients with Sepsis. Critical care medicine, 44(10), 1851-1860. https://doi.org/10.1097/CCM.0000000000001827