Urinary biomarkers IGFBP7 and TIMP-2 in the ICU: a multicenter prospective study on acute kidney injury outcomes

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Background: Acute kidney injury (AKI) is prevalent in critically ill patients, contributing to high morbidity, mortality, and healthcare costs. Early detection and differentiation between transient and persistent AKI are critical for guiding timely interventions. This study evaluates the NephroCheck® score, based on Tissue inhibitor of metalloproteinases-2 (TIMP-2) and Insulin-like growth factor-binding protein 7 (IGFBP7) biomarkers. The primary objective was to assess its ability to predict AKI risk and AKI subtype within the first seven days of Intensive Care Unit (ICU) admission. Secondary objectives included evaluating its association with the need for renal replacement therapy (RRT) and overall ICU outcomes in a heterogeneous critical care population. Methods: This prospective, multicenter observational study included 455 ICU patients from five hospitals in Barcelona, Spain. Biomarker analysis was conducted on urine samples collected at admission, and AKI was classified according to the kidney Disease: Improving Global Outcomes (KDIGO) criteria. Patients were grouped by TIMP-2·IGFBP7 values and AKI subtypes. Data was analyzed using Stata version 18.0 (StataCorp, College Station, TX). Results: AKI occurred in 51% of patients; with 29% transient and 71% persistent. High TIMP-2·IGFBP7 (TIMP-2·IGFBP7 > 2.0) levels were significantly associated with AKI (OR 19.44; 95% CI [2.57-146.5], p = 0.004), persistent AKI (OR 4.3; 95% CI [1.61-11.41], p = 0.003), and RRT requirements (OR 3.93; 95% CI [1.34-11.47], p = 0.012). Patients with high TIMP-2·IGFBP7 had longer ICU stays, more severe AKI, increased RRT duration, and higher mortality rates. TIMP-2·IGFBP7 values correlated positively with ICU and in-hospital mortality and reduced 90-day survival. Conclusion: TIMP-2·IGFBP7 showed modest performance for early AKI detection, identifying RRT requirements and risk stratification in critically ill patients. While moderately effective for predicting outcomes, its role in differentiating transient from persistent AKI remains inconsistent. Further research is warranted to optimize TIMP-2·IGFBP7 guided interventions and explore its application in diverse AKI etiologies.

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