Comparison of urinary TIMP-2 and IGFBP7 cut-offs to predict acute kidney injury in critically ill patients

Abstract

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.

Insulin-Like Growth Factor Binding Protein 7 Predicts Renal and Cardiovascular Outcomes in the Canagliflozin Cardiovascular Assessment Study

“…Recent work regarding IGFBP7 has mainly focused on the biomarker in patients with heart failure (11)(12)(13)(14)(15)(16), where concentrations of IGFBP7 are higher in those with more severe disease and are associated with structural abnormalities of the heart (15,16). Though urinary IGFBP7 has been associated with acute kidney injury (8), no data exist regarding the role of urine or circulating IGFBP7 to predict chronic kidney outcomes in patients with type 2 diabetes. Our results are thus highly novel and considerably extend results for blood-based measurement of IGFBP7 for renal and cardio-renal outcomes.…”

“…It is a member of the senescence-associated secretory phenotype with pluripotent in vivo roles, notably including induction of G1/S cell cycle arrest (7). Prior work has linked urinary concentrations of IGFBP7 (measured together with tissue inhibitor of metalloproteinase-2) for prediction of acute kidney injury (8).…”

Acute kidney injury in the critically ill: an updated review on pathophysiology and management

“…High sensitivity (> 0.3) and high specificity (> 2.0) cutoffs have been defined, allowing risk stratification [13]. Two recent meta-analyses showed an AUROC 0.83 for the prediction of AKI within 24 h in cardiac surgery [14] and 0.74 for the prediction of stage 2 and 3 within 12 h in the critically ill [15]. A meta-analysis on the accuracy of urinary NGAL showed an AUROC of 0.75 for severe AKI with cut-offs of 12 ng/ml for 95% sensitivity and 580 ng/ ml for 95% specificity [16].…”

Rational selection of a biomarker panel targeting unmet clinical needs in kidney injury

“…Evidence of clinical performance for the prediction of AKI, AKI severity and RRT in critically ill patients was obtained from meta-analyses. Meta-analyses were available for the urinary biomarkers kidney injury molecule-1 (KIM-1) [ 50 ], neutrophil gelatinase-associated lipocalin (NGAL) [ 51 – 56 ], interleukin-18 (IL-18) [ 52 , 54 , 57 , 58 ], N -acetyl-β- d -glucosaminidase (NAG) [ 54 ], cystatin C [ 52 , 54 , 59 ], liver-type fatty acid binding protein (L-FABP) [ 54 , 60 ], metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) [ 52 , 61 – 64 ] (Additional file 2 : Table S2.2).…”