Urinary [TIMP-2] × [IGFBP7] and serum procalcitonin to predict and assess the risk for short-term outcomes in septic and non-septic critically ill patients

Background: Biomarkers can play a critical role by facilitating diagnosis and stratifcation of disease, as well as assessment or prediction of disease severity. Urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein 7 product ([TIMP-2]×[IGFBP7]) predict the development and progression of AKI and recently procalcitonin (PCT), a widely used biomarker for sepsis diagnosis and management, has been associated with AKI occurrence in ICU patients. To assess combinations of [TIMP-2]×[IGFBP7] and PCT results for prediction and risk stratifcation of short-term outcomes in septic and non-septic patients, a retrospective cohort analysis of critically ill patients was performed in a multidisciplinary ICU. ROC curve analysis was used in order to evaluate predictive performance of combined results of [TIMP-2]×[IGFBP7] and PCT at the time of admission for AKI development. To verify the utility of adding [TIMP-2]×[IGFBP7] and PCT results for risk assessment, we evaluated the predictive value of having a singlemarker positivity compared to a double-marker positivity using the widely used cut-of of 0.3 (ng/mL)2 /1000 for [TIMP-2]×[IGFBP7] and 0.5 μg/L for PCT. Risk assessment for AKI occurrence within 48 h, acute kidney disease (AKD) and mortality at 7 days was performed by logistic/Cox regression analysis. Results: 433 patients were analysed, of whom 168 had AKI within 48 h (93 septic and 65 non-septic patients). Combination of [TIMP-2]×[IGFBP7] and PCT showed a good predictive ability for AKI occurrence (AUC 0.81, 95% CI 0.77–0.86, p<0.001, Sens 78%, Spec 73%). Combinations of biomarkers increased the odd ratios (OR) considerably. A single-marker positivity showed a fourfold risk increase, while the double-marker positivity a 26-fold risk increase for AKI occurrence. Moreover, the double-marker positivity showed an elevated risk for AKD at 7 days in non-septic patients (OR 15.9, 95% CI 3,21–73,57, p<0.001) and for mortality within 7 days in septic patients (HR 4.1, 95% CI 1.4–11.8, p=0.001). Conclusions: Although combining the results of [TIMP-2]×[IGFBP7] and PCT may be a useful tool to identify and stratify ICU patients at high risk for septic AKI and short-term adverse outcomes, data should be confrmed in a large prospective study.