Comparison of urinary TIMP-2 and IGFBP7 cut-offs to predict acute kidney injury in critically ill patients A PRISMA-compliant systematic review and meta-analysis

Background: Tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) are recently identified urinary biomarkers of acute kidney injury (AKI) in critically ill patients. Because their predictive accuracies vary widely, a meta-analysis was performed to evaluate the accuracy of previously reported urinary TIMP-2 and IGFBP7 cut-offs for predicting AKI. Methods: This meta-analysis was reported following the guideline of PRISMA. Four databases, PubMed, the Cochrane Library, the ISI Web of Knowledge, and Embase, were systematically searched from inception to June 2018 by 2 investigators, who independently selected studies, extracted relevant data, and evaluated study quality. A bivariate model was used to calculate the pooled estimates. Results: The search identified 5 studies with 1619 critically ill patients. Urinary TIMP-2 and IGFBP7 cut-off points of 0.3 (ng/ml)(2)/1000 had a sensitivity of 0.89 [95% confidence interval (CI) 0.85-0.93], a specificity of 0.48 (95% CI 0.45-0.51) and a diagnostic odds ratio (DOR) of 8.33 (95% CI 5.55-12.52). The area under the curve (AUC) estimated by the summary receiver operating characteristic (SROC) curve was 0.748. Based on 891 critically ill patients from 4 studies, urinary TIMP-2 and IGFBP7 cut-off points of 2.0 (ng/ml)(2)/1000 had a sensitivity of 0.45 (95% CI 0.37-0.53), a specificity of 0.93 (95% CI 0.91-0.95) and a DOR of 11.43 (95% CI 7.43-17.57). The AUC estimated by SROC was 0.844. Conclusion: Cut-off values around 0.3 (ng/ml)(2)/1000 (high sensitivity) and 2.0 (ng/ml)(2)/1000 (high specificity) could be accurate surrogate biomarkers predicting AKI in critically ill patients. The urinary TIMP-2 and IGFBP7 cut-off point of 2.0 (ng/mL)(2)/1000 appears to have the highest overall accuracy. Trial registration: PROSPERO registration number 2018: CRD42018084457 Registered on 11 February 2018.