Research Article: Diagnostic Value of Urine Tissue Inhibitor of Metalloproteinase-2 and Insulin-Like Growth Factor-Binding Protein 7 for Acute Kidney Injury: A Meta-Analysis

Date Published: January 20, 2017

Publisher: Public Library of Science

Author(s): Yuanyuan Su, Zhiyan Gong, Yan Wu, Yuan Tian, Xiaohui Liao, Umberto Simeoni.


Tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein-7 (IGFBP7) are both involved in renal tubular epithelial cell cycle arrest in acute kidney injury (AKI). Several recent studies showed that urine TIMP-2 times IGFBP7 ([TIMP-2]*[IGFBP7]) is a promising biomarker to predict AKI.

The aim of this meta-analysis was to assess the diagnostic value of urine [TIMP-2]*[IGFBP7] for early diagnosis of AKI. Relevant studies were retrieved from the PubMed, EMBASE, and Cochrane Library databases. The sensitivity and specificity were determined, and summary receiver operating characteristic (SROC) curves were constructed.

Ten full-text prospective studies were included in this meta-analysis. The estimated sensitivity of urine [TIMP-2]*[IGFBP7] for the early diagnosis of AKI was 0.84 (95% CI = 0.80–0.88) and the specificity was 0.57 (95%CI = 0.55–0.60). The SROC analysis showed an area under the curve of 0.8813.

The limited number of included studies, small sample size, unpublished negative results and language limitation might have affected the evaluation.

Urine [TIMP-2]*[IGFBP7] is a promising candidate for early detection of AKI, especially in ruling-out AKI. However, the potential of this biomarker should be validated in larger studies with a broader spectrum of clinical settings.

Partial Text

Acute kidney injury (AKI) is a common and serious clinic syndrome that presents as a rapid decrease in kidney function over a short period of time and is associated with a high risk of morbidity and mortality. Various factors that are known to induce AKI include cardiac surgery, infection, and drug toxicity, among others. The morbidity rate of AKI is about 5% among inpatients and 30%-50% among those in the intensive care unit (ICU). Among patients with AKI, about 6% will require dialysis, which is associated with a mortality rate of 60% [1–3]. The prognosis of AKI is dependent on early diagnosis and treatment. Therefore, early diagnosis is a key to successful AKI treatment [4].

Early treatment can improve the prognosis or even reverse the acute renal damage in AKI. Various biomarkers of AKI have been evaluated in recent years, including NGAL, KIM-1, L-FABP, and CysC, among others. These recently identified biomarkers seem to behave better as diagnostic values during the early stage of AKI than more conventional biomarkers in some studies, but there are some disadvantages. For example, a study by Kooiman et al. [23] found that KIM-1 and NGAL did not fluctuate in 511 patients monitored by post-intravenous contrast-enhanced computed tomography, including those with contrast-induced AKI (CI-AKI). This result raises concern about the accuracy of NGAI and KIM-1 in CI-AKI. In addition, NGAL is reportedly influenced by many other common clinical factors, including baseline renal function, inflammation, pregnancy, cancer, etc. [24–27]. IL-18 was reported to be affected by inflammation [28]. Furthermore, the concentrations of NGAL, KIM-1, IL-18 and L-FABP are higher in patients with chronic kidney disease than healthy controls [29–35], which might interfere in the differentiation between AKI and chronic kidney disease. Hence, these biomarkers are not sufficient to differentially diagnose AKI.

The result of this meta-analysis demonstrated that the AUC-ROC for diagnostic accuracy of urine [TIMP-2]*[IGFBP7] for AKI was good. The summary AUC-ROC, sensitivity and specificity of this meta-analysis were 0.8813, 0.84 and 0.57, respectively.




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