Diagnostic value of urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein 7 for acute kidney injury: a meta-analysis

Abstract

BackgroundTissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7), inducers of G1 cell cycle arrest, are two recently discovered good biomarkers for early diagnosis of acute kidney injury (AKI). To obtain a more robust performance measurement, the present meta-analysis was performed, pooling existing studies.MethodsLiterature in the MEDLINE (via PubMed), Ovid, Embase, and Cochrane Library databases was systematically searched from inception to 12 October 2016. Studies that met the set inclusion and exclusion criteria were identified by two independent investigators. The diagnostic value of urinary [TIMP-2] × [IGFBP7] for AKI was evaluated by pooled sensitivity, specificity, likelihood ratio (LR), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curve analyses. The causes of heterogeneity were explored by sensitivity and subgroup analyses.ResultsA total of nine published and eligible studies assessing 1886 cases were included in this meta-analysis. Early diagnostic value of urinary [TIMP-2] × [IGFBP7] for AKI was assessed using a random-effects model. Pooled sensitivity and specificity with corresponding 95% CIs were 0.83 (95% CI 0.79–0.87, heterogeneity I 2 = 68.8%) and 0.55 (95% CI 0.52–0.57, I 2 = 92.9%), respectively. Pooled positive LR, negative LR, and DOR were 2.37 (95% CI 1.87–2.99, I 2 = 82.6%), 0.30 (95% CI 0.21–0.41, I 2 = 43.4%), and 9.92 (95% CI 6.09–16.18, I 2 = 38.5%), respectively. The AUC estimated by SROC was 0.846 (SE 0.027) with a Q* value of 0.777 (SE 0.026). Sensitivity analysis indicated that one study significantly affected the stability of pooled results. Subgroup analysis showed that population setting and AKI threshold were the key factors causing heterogeneity in pooled sensitivity and specificity.ConclusionsOn the basis of recent evidence, urinary [TIMP-2] × [IGFBP7] is an effective predictive factor of AKI.Trial registrationPROSPERO registration number: CRD42016051186. Registered on 10 November 2016.

Prognostic value of cell cycle arrest biomarkers in patients at high risk for acute kidney injury: A systematic review and meta‐analysis

“…Therefore, multiple studies have focused on early detection of renal damage in order to implement early intervention, and decrease morbidity and mortality of AKI . In a previous study, we confirmed the predictive values of tissue inhibitor of metalloproteinase‐2 (TIMP‐2) and insulin‐like growth factor binding protein 7 (IGFBP7) for AKI . However, the prognostic value of urinary [TIMP‐2]·[IGFBP7] in predicting the need for RRT and mortality remains unclear.…”

“…The predictive value of urinary [TIMP‐2]·[IGFBP7] for AKI was discussed in our previous study . Further, Su Y also identified the diagnostic value of this parameter for AKI.…”

“…5,6 In a previous study, we confirmed the predictive values of tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) for AKI. 7 However, the prognostic value of urinary [TIMP-2]·[IGFBP7] in predicting the need for RRT and mortality remains unclear. Predicting major adverse kidney events in patients at high risk for AKI may provide useful information for clinical decision-making and early implementation of supportive measures, reducing the need for RRT as well as mortality.…”

“…[9][10][11] Accumulating evidence suggests that urinary [TIMP-2]·[IGFBP7] of 0.3 (ng/mL) 2 /1000 indicates a high risk for AKI. 7 Meanwhile, greater values of urinary [TIMP-2]·[IGFBP7] are promising predictors of RRT requirement or mortality. We systematically searched the literature and performed the current systematic review to evaluate the prognostic accuracy of urinary [TIMP-2]•[IGFBP7] in predicting the need for RRT as well as mortality.…”

“…Renal cells subsequently repair the injury of genomic integrity, cellular senescence, and apoptosis through G1 cell‐cycle arrest effectors . Accumulating evidence suggests that urinary [TIMP‐2]·[IGFBP7] of 0.3 (ng/mL) 2 /1000 indicates a high risk for AKI . Meanwhile, greater values of urinary [TIMP‐2]·[IGFBP7] are promising predictors of RRT requirement or mortality.…”