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

Abstract

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 singlemarker positivity compared to a double-marker positivity using the widely used cutoff 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.

Use of Biomarkers to Identify Acute Kidney Injury to Help Detect Sepsis in Patients With Infection

“…Pooled results for 23 studies including more than 150,000 non-ICU patients illustrate that quick SOFA has poor sensitivity for sepsis mortality (51%) and organ failure (47%) ( 15 ). Numerous studies have shown that urinary (TIMP-2) × (IGFBP7) is sensitive and specific for AKI including for patients with sepsis ( 5 , 16 – 18 ). Many patients with infection are admitted to hospital, and, in the absence of shock or respiratory failure, few are admitted to ICU.…”

Prognostic Value of Systemic Immune-Inflammation Index among Critically Ill Patients with Acute Kidney Injury: A Retrospective Cohort Study

“…Inflammation plays a significant role in the occurrence and development of AKI [ 8 , 9 , 10 ]. Many well-known inflammatory markers, including neutrophils [ 11 ], platelets [ 12 , 13 ] and procalcitonin [ 14 ] have been shown to be related to AKI. However, focusing on just one indicator is of limited use, as these biomarkers are always affected by other confounding factors.…”

Epidemiology and Outcomes of Acute Kidney Diseases: A Comparative Analysis

“…The limitations of using filtration markers, such as creatinine, to diagnose and assess recovery from acute and subacute kidney damage are well recognized. Although preliminary work assessing the utility of biomarkers to predict AKD is underway, these alternative measures of kidney function require further validation in this setting prior to clinical use [11, 15].…”

“…Despite this, AKD has not been systematically studied, and its relationship with long-term clinical outcomes is poorly understood. Data from previous studies have been variably limited by short follow-up time [7, 8], non-consensus definitions of exposure [7-11], clinically enriched populations [10, 12-16], lack of adjustment for confounders [7, 9, 12, 14-16], and pooling of heterogeneous data from community and hospital settings [17]. The only published study to examine AKD without AKI included patients with unknown baseline kidney function [17].…”