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2016 ; 44
(10
): 1851-60
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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
#MMPMID27355527
Honore PM
; Nguyen HB
; Gong M
; Chawla LS
; Bagshaw SM
; Artigas A
; Shi J
; Joannes-Boyau O
; Vincent JL
; Kellum JA
Crit Care Med
2016[Oct]; 44
(10
): 1851-60
PMID27355527
show ga
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.