Predictive value of urinary cell cycle arrest biomarkers for all cause-acute kidney injury: a meta-analysis

The cell cycle arrest markers tissue inhibitor metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) have been identified as potential biomarkers of acute kidney injury (AKI) in critically ill adults in intensive care units and cardiac surgery-associated AKI (CSA-AKI). However, the clinical impact on all-cause AKI remains unclear. Here, we report a meta-analysis performed to evaluate the predictive value of this biomarker for all-cause AKI. The PubMed, Cochrane, and EMBASE databases were systematically searched up to April 1, 2022. We used the Quality Assessment Tool for Diagnosis Accuracy Studies (QUADAS-2) to assess the quality. We extracted useful information from these studies and calculated the sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC). Twenty studies with 3625 patients were included in the meta-analysis. The estimated sensitivity of urinary TIMP-2 × IGFBP7 in the diagnosis of all-cause AKI was 0.79 (95% CI 0.72, 0.84), and the specificity was 0.70 (95% CI 0.62, 0.76). The value of urine TIMP-2 × IGFBP7 in the early diagnosis of AKI was assessed using a random effects model. The pooled positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were 2.6 (95% CI 2.1, 3.3), 0.31 (95% CI 0.23, 0.40), and 8 (95% CI 6, 13), respectively. The AUROC was 0.81 (95% CI 0.78-0.84). No significant publication bias was observed in eligible studies. Subgroup analysis indicated that the diagnostic value was related to the severity of AKI, time measurement, and clinical setting. This study shows that urinary TIMP-2 × IGFBP7 is a reliable effective predictive test for all cause-AKI. However, whether and how urinary TIMP-2 × IGFBP7 can be used in clinical diagnosis still requires further research and clinical trials.