Beyond creatinine: diagnostic accuracy of emerging biomarkers for AKI in the ICU–a systematic review

Abstract

Background: Acute kidney injury (AKI) affects 30–50% of critically ill patients and is associated with increased mortality, longer ICU stays, and chronic kidney dysfunction. Current diagnostic markers, serum creatinine and urine output are delayed and often insensitive. Novel biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and the combined urinary assay of tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 (TIMP-2·IGFBP7) have emerged as promising tools for early AKI detection. Objective: To systematically evaluate the diagnostic accuracy of NGAL, KIM-1, and TIMP-2·IGFBP7 in predicting AKI in critically ill adults. Methods: A systematic search of PubMed, Embase, and Cochrane Library was conducted for studies from January 2015 to April 2025. Eligible studies assessed the diagnostic accuracy of NGAL, KIM-1, or TIMP-2·IGFBP7 in adult ICU patients and reported sensitivity, specificity, or AUC. Methodological quality was appraised using QUADAS-2. PROSPERO registration: CRD420251038322. Results: Thirty-five studies were included: 13 assessed NGAL, 7 KIM-1, and 15 TIMP-2·IGFBP7. NGAL showed sensitivity of 65–89% and specificity of 60–85% (AUC: 0.70–0.91). KIM-1 showed moderate performance (AUC: 0.64–0.80). TIMP-2·IGFBP7, especially with higher cutoffs, demonstrated high specificity but variable sensitivity. Differences in assay thresholds, timing, and AKI definitions contributed to heterogeneity. Conclusion: NGAL and TIMP-2·IGFBP7 show the most consistent performance for early AKI detection in ICU settings. Standardized multicenter studies are needed to confirm clinical utility and support integration into AKI diagnostic workflows.