Cell-cycle arrest biomarkers in urine to predict acute kidney injury in septic and non-septic critically ill patients

尿液中细胞周期阻滞生物标志物可用于预测脓毒症和非脓毒症危重患者的急性肾损伤

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Abstract

PURPOSE: To analyse the usefulness of the composite index of the tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) as urinary biomarkers for the early prediction of AKI in septic and non-septic patients. METHODS: This is a prospective, observational study including patients admitted to ICU from acute care departments and hospital length of stay <48 h. The main exclusion criteria were pre-existing eGFR <30 mL/min/1.73 m(2) and hospitalisation 2 months prior to current admission. The [TIMP-2]·[IGFBP7] index was analysed twice, within the first 12 h of ICU admission. RESULTS: The sample included 98 patients. AKI incidence during ICU stay was 50%. Sepsis was diagnosed in 40.8%. Baseline renal variables were comparable between subgroups except for a higher baseline eGFR in non-septic patients. Patients were stratified based on the presence of AKI and their highest level of [TIMP-2]·[IGFBP7] within the first 12 h of stay. [TIMP-2]·[IGFBP7] index values were dependent on the incidence of AKI but not of sepsis. [TIMP-2]·[IGFBP7] values were significantly related to AKI severity according to AKIN criteria (p < 0.0001). The AUROC curve to predict AKI of the worst [TIMP-2]·[IGFBP7] index value was 0.798 (sensitivity 73.5%, specificity 71.4%, p < 0.0001). Index values below 0.8 ruled out any need for renal replacement (NPV 100%), whereas an index >0.8 predicted a rate of AKI of 71% and AKIN ≥ 2 of 62.9%. CONCLUSIONS: In our study, urinary [TIMP-2]·[IGFBP7] was an early predictor of AKI in ICU patients regardless of sepsis. Besides, index values <0.8(ng/mL)(2)/1000 ruled out the need for renal replacement.

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