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Crit Care Med. 2016 Oct;44(10):1851-60. doi: 10.1097/CCM.0000000000001827.

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.

Author information

1
1Department of Intensive Care Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, VUB School of Medicine, Brussels, Belgium.2Department of Medicine, Pulmonary and Critical Care Medicine and Department of Emergency Medicine, Loma Linda University, Loma Linda, CA.3Division of Critical Care Medicine, Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY.4Department of Medicine, Division of Intensive Care Medicine and Division of Nephrology, Veterans Affairs Medical Center, and Department of Anesthesiology and Critical Care Medicine, George Washington University Medical Center, Washington, DC.5Division of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.6Critical Care Center, Sabadell Hospital, CIBER de Enfermedades Respiratorias, Corporacó Sanitaria Universitaria Parc Tauli, Autonomous University of Barcelona, Sabadell, Spain.7Walker Biosciences, Carlsbad, CA.8Department of Anesthesiology and Critical Care Medicine 2, Hospital Haut Leveque, University of Bordeaux 2, Bordeaux, France.9Department of Intensive Care, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium.10The Center for Critical Care Nephrology, CRISMA (Clinical Research, Investigation, and Systems Modeling of Acute Illness) Center, Pittsburgh, PA.11Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA.

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)/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.

PMID:
27355527
PMCID:
PMC5089124
DOI:
10.1097/CCM.0000000000001827
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Dr. Honore had also received research grants from Baxter, AM Pharma, Bellco, and Pfizer. Dr. Nguyen’s institution received funding from Astute Medical. Dr. Gong is supported by grants from the National Institutes of Health. Dr. Gong’s institution received funding from Astute. Dr. Chawla is employed by La Jolla Pharmaceutical Company and has received consulting fees from Astute Medical, Alere Medical, AM Pharma, and Baxter Medical, and has licensed unrelated technologies through George Washington University to Astute Medical. Dr. Bagshaw is supported by a Canada Research Chair in Critical Care Nephrology. Dr. Bagshaw has received consulting fees from Baxter Healthcare, Masimo. Dr. Artigas reports consultation fees from Baxter, Rubio and Grifols. Dr. Artigas received funding from Rubio Co and Grifols (consultancy and lectures) and disclosed other support (Ferrer farma). His institution received funding from Hill-Rom research grant. Dr. Shi received consulting fees from Astute Medical and has family disclosures (her husband also received consulting fees from Astute Medical). Dr. Joannes-Boyau received consulting fees from Gambro Baxter, B. Braun, and Merck Sharp & Dohme. His institution received funding from Astute. Dr. Kellum has received consulting fees from Astute Medical, Alere, Aethlon, AM Pharma, Cytosorbents, Bard, Fresenius, Baxter, Abbott Diagnostics, and Spectral Diagnostics. Dr. Kellum has also received research grants from Astute Medical, Alere, Cytosorbents, Bard, Baxter, and Spectral Diagnostics and has licensed unrelated technologies through the University of Pittsburgh to Astute Medical, and Cytosorbents; received funding from Astute Medical, Alere, Aethlon; other: Received consulting fees AM Pharma, Cytosorbents, Bard, Fresenius, Baxter, Abbott Diagnostics, and Spectral Diagnostics. He disclosed other support (Licensed unrelated technologies through University of Pittsburgh to Astute Medical and Cytosorbents). His institution received funding from Astute Medical, Alere, and Cytosorbents. Dr. Vincent disclosed that he does not have any potential conflicts of interest.

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