Abstract
BackgroundThe urine biomarkers tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) have been validated for predicting and stratifying AKI. In this study, we analyzed the utility of these biomarkers for distinguishing between transient and persistent AKI in the early phase of septic shock.MethodsWe performed a prospective, multicenter study in 11 French ICUs. Patients presenting septic shock, with the development of AKI within the first 6 h, were included. Urine [TIMP-2]*[IGFBP7] was determined at inclusion (0 h), 6 h, 12 h, and 24 h. AKI was considered transient if it resolved within 3 days. Discriminative power was evaluated by receiver operating characteristic (ROC) curve analysis.ResultsWe included 184 patients, within a median [IQR] time of 1.0 [0.0–3.0] h after norepinephrine (NE) initiation; 100 (54%) patients presented transient and 84 (46%) presented persistent AKI. Median [IQR] baseline urine [TIMP-2]*[IGFBP7] was higher in the persistent AKI group (2.21 [0.81–4.90] (ng/ml)2/1000) than in the transient AKI group (0.75 [0.20–2.12] (ng/ml)2/1000; p < 0.001). Baseline urine [TIMP-2]*[IGFBP7] was poorly discriminant, with an AUROC [95% CI] of 0.67 [0.59–0.73]. The clinical prediction model combining baseline serum creatinine concentration, baseline urine output, baseline NE dose, and baseline extrarenal SOFA performed well for the prediction of persistent AKI, with an AUROC [95% CI] of 0.81 [0.74–0.86]. The addition of urine [TIMP-2]*[IGFBP7] to this model did not improve the predictive performance.ConclusionsUrine [TIMP-2]*[IGFBP7] measurements in the early phase of septic shock discriminate poorly between transient and persistent AKI and do not improve clinical prediction over that achieved with the usual variables.Trial registrationNCT02812784
Highlights
The urine biomarkers tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factorbinding protein 7 (IGFBP7) have been validated for predicting and stratifying acute kidney injury (AKI)
Most recent studies assessing the ability of urine biochemistry and derived indices to discriminate between transient and persistent AKI in critically ill patients have reported conflicting findings and relatively limited performances incompatible with use in clinical practice [9,10,11,12,13,14,15]
Population characteristics We screened 345 patients screened during the study period, 184 (166 (90%) at the five principal centers) of whom were included a median [Interquartile range (IQR)] of 1.0 [0.0–3.0] h after the initiation of norepinephrine treatment (Fig. 1)
Summary
The urine biomarkers tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factorbinding protein 7 (IGFBP7) have been validated for predicting and stratifying AKI. We analyzed the utility of these biomarkers for distinguishing between transient and persistent AKI in the early phase of septic shock. A recent study estimated that 68% of patients with sepsis had AKI at admission, with 40% presenting severe AKI and 27% subsequently undergoing renal replacement therapy (RRT) during intensive care unit (ICU) stay [3]. Most recent studies assessing the ability of urine biochemistry and derived indices to discriminate between transient and persistent AKI in critically ill patients have reported conflicting findings and relatively limited performances incompatible with use in clinical practice [9,10,11,12,13,14,15]
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