Evaluation of urinary tissue inhibitor of metalloproteinase-2 in acute kidney injury: a prospective observational studyReportar como inadecuado

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Critical Care

, 18:716

First Online: 19 December 2014Received: 27 July 2014Accepted: 11 December 2014


IntroductionTissue inhibitor of metalloproteinase-2 TIMP-2 is an emerging acute kidney injury AKI biomarker. We evaluated the performance of urinary TIMP-2 in an adult mixed ICU by comparison with other biomarkers that reflect several different pathways of AKI.

MethodsIn this study, we prospectively enrolled 98 adult critically ill patients who had been admitted to the adult mixed ICU. Urinary TIMP-2 and N-acetyl-β-d-glucosaminidase NAG and plasma neutrophil gelatinase-associated lipocalin NGAL, interleukin-6 IL-6 and erythropoietin EPO were measured on ICU admission. We evaluated these biomarkers’ capability of detecting AKI and its severity as determined by using the Kidney Disease Improving Global Outcomes serum creatinine criteria, as well as its capacity to predict in-hospital mortality. The impact of sepsis, the leading cause of AKI in ICUs, was also evaluated.

ResultsWe found AKI in 42 patients 42.9%. All biomarkers were significantly higher in AKI than in non-AKI. In total, 27 patients 27.6% developed severe AKI. Urinary TIMP-2 was able to distinguish severe AKI from non-severe AKI with an area under the receiver operating characteristic curve AUC-ROC of 0.80 95% confidence interval, 0.66 to 0.90. A total of 41 cases 41.8% were complicated with sepsis. Although plasma NGAL and IL-6 were increased by sepsis, urinary TIMP-2 and NAG were increased not by sepsis, but by the presence of severe AKI. Plasma EPO was increased only by septic AKI. In-hospital mortality was 15.3% in this cohort. Urinary TIMP-2 and NAG, and plasma NGAL, were significantly higher in non-survivors than in survivors, although plasma IL-6 and EPO were not. Among the biomarkers, only urinary TIMP-2 was able to predict in-hospital mortality significantly better than serum creatinine.

ConclusionUrinary TIMP-2 can detect severe AKI with performance equivalent to plasma NGAL and urinary NAG, with an AUC-ROC value higher than 0.80. Furthermore, urinary TIMP-2 was associated with mortality. Sepsis appeared to have only a limited impact on urinary TIMP-2, in contrast to plasma NGAL.

AbbreviationsADQIAcute Dialysis Quality Initiative

AKIAcute kidney injury

APACHEAcute Physiology and Chronic Health Evaluation

AUC-ROCArea under the receiver operating characteristic curve


ICUIntensive care unit

IDIIntegrated discrimination improvement

IGFBP-7Insulin-like growth factor-binding protein-7


KDIGOKidney Disease Improving Global Outcomes

L-FABPL-type fatty acid-binding protein


NGALNeutrophil gelatinase-associated lipocalin

NRINet reclassification improvement

ROCReceiver operating characteristic

TIMP-2Tissue inhibitor of metalloproteinase-2

Electronic supplementary materialThe online version of this article doi:10.1186-s13054-014-0716-5 contains supplementary material, which is available to authorized users.

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Autor: Tetsushi Yamashita - Kent Doi - Yoshifumi Hamasaki - Takehiro Matsubara - Takeshi Ishii - Naoki Yahagi - Masaomi Nangaku -

Fuente: https://link.springer.com/

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