Diagnostic prediction of urinary TIMP-2 x IGFBP7 for acute kidney injury: A meta-analysis exploring detection time and cutoff levels

Acute kidney injury (AKI) most commonly occurs in critically ill and postoperative patients. Tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) are two newly-identified urinary biomarkers that can help to detect early AKI, yet their predictive accuracies range widely. Here, we conduct a systematic meta-analysis to evaluate the diagnostic values of TIMP-2 x IGFBP7 for AKI at different detection times and cutoff levels. Ten studies were meta-analyzed on 1606 patients. Overall, urinary TIMP-2 x IGFBP7 had a pooled sensitivity of 58% and specificity of 79%. Subgroup analysis showed that the sensitivity and specificity were 0.72 and 0.58 with a cutoff value of 0.3 (ng/mL)2/1000, and 0.38 and 0.94 with a cutoff value of 2.0 (ng/mL)2/1000, respectively. Moreover, when 0.3 was chosen as the cutoff value, restricting analysis to patients who were tested within 4 hours showed a sensitivity of 0.71 and specificity of 0.73, with the AUROC of 0.75. When 2.0 was chosen as the cutoff value, the sensitivity and specificity were 0.43 and 0.93, respectively in patients who were tested within 24 hours, with the AUROC of 0.70. In summary, urinary TIMP-2 x IGFBP7 can predict the occurrence of AKI with moderate diagnostic accuracy. In the earlier administrative periods (less than 4 hours), 0.3 (ng/mL)2/1000 is recommended to be used; whereas for patients who were administrated more than 24 hours, 2.0 (ng/mL)2/1000 is more appropriate.