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 stratification 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 stratification 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 single-marker positivity compared to a double-marker positivity using the widely used cut-off 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 confirmed in a large prospective study.

Routine Adoption of Urinary [IGFBP7]∙[TIMP-2] to Assess Acute Kidney Injury at Any Stage 12 hours After Intensive Care Unit Admission: a Prospective Cohort Study.

The urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 ([TIMP-2]∙[IGFBP7]) have been introduced to improve risk prediction of severe acute kidney injury (AKI) within 12 hours of measurement. We performed a prospective cohort study to evaluate if the predictive value of [TIMP-2]∙[IGFBP7] for AKI might continue after 12 hours. We enrolled 442 critically ill adult patients from June to December 2016. Urine samples were collected at admission for [TIMP-2]∙[IGFBP7] measurement. Baseline patient characteristics were recorded including patients' demographics, prior health history, and the main reason for admission to build a logistic regression model to predict AKI. AKI occurrence differed between patients with [TIMP-2]∙[IGFBP7] ≤0.3 and >0.3 (ng/ml)2/1000 (31.9% and 68.10% respectively; p < 0.001). Patients with AKI had higher biomarker values compared to those without AKI (0.66 (0.21-2.84) vs 0.22 (0.08-0.63) (ng/ml)2/1000; p < 0.001). [TIMP-2]∙[IGFBP7] at ICU admission had a lower performance in predicting AKI at any stage within 48 hours and 7 days after measurement (area under the receiver operating characteristic curve (AUC) equal to 0.70 (95%CI 0.65-0.76), AUC 0.68 (95%CI 0.63-0.73)). In the logistic regression model, 0.1 (ng/ml)2/1000-unit increment was likely to increase the risk of AKI by 2% (p = 0.002).

Development and validation of quick Acute Kidney Injury-score (q-AKI) to predict acute kidney injury at admission to a multidisciplinary intensive care unit.

AKI is associated with increased risk of death, prolonged length of stay and development of de-novo chronic kidney disease. The aim of our study is the development and validation of prediction models to identify the risk of AKI in ICU patients up to 7 days. We retrospectively recruited 692 consecutive patients admitted to the ICU at San Bortolo Hospital (Vicenza, Italy) from 1 June 2016 to 31 March 2017: 455 patients were treated as the derivation group and 237 as the validation group. Candidate variables were selected based on a literature review and expert opinion. Admission eGFR< 90 ml/min /1.73 mq (OR 2.78; 95% CI 1.78-4.35; p<0.001); SOFAcv ≥ 2 (OR 2.23; 95% CI 1.48-3.37; p<0.001); lactate ≥ 2 mmol/L (OR 1.81; 95% CI 1.19-2.74; p = 0.005) and (TIMP-2)•(IGFBP7) ≥ 0.3 (OR 1.65; 95% CI 1.08-2.52; p = 0.019) were significantly associated with AKI. For the q-AKI score, we stratified patients into different AKI Risk score levels: 0-2; 3-4; 5-6; 7-8 and 9-10. In both cohorts, we observed that the proportion of AKI patients was higher in the higher score levels.