TIMP-2 and IGFBP7 for the differentiation of functional and intrinsic pediatric acute kidney injury

Abstract Background Acute kidney injury (AKI) is frequent in critically ill neonates and children, increasing morbidity and mortality. Early distinction between functional and intrinsic (structural) AKI is crucial due to divergent management strategies. While urinary calprotectin shows promise in differentiating AKI, urinary tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding-protein 7 (IGFBP7) lack data in pediatrics. This study evaluated [TIMP-2]•[IGFBP7] ability to differentiate functional from intrinsic AKI in neonates and children. Methods A total of 179 neonates and children (0–18 years) were included: 54 with intrinsic AKI, 22 with functional AKI, 44 without AKI and 59 apparently healthy children. Urinary [TIMP-2]•[IGFBP7] was compared to urinary calprotectin, fractional excretion of sodium (FE Na ) and protein-to-creatinine ratio. Results ROC analysis for AKI diagnosis yielded AUCs of 0.76 (95% CI: 0.68–0.83) for [TIMP-2]•[IGFBP7], 0.69 (0.61–0.77) for calprotectin, 0.75 (0.66–0.84) for FE Na , and 0.88 (0.82–0.94) for protein-to-creatinine ratio. For differentiating functional from intrinsic AKI, AUCs were 0.68 (0.55–0.82) for [TIMP-2]•[IGFBP7], 0.85 (0.75–0.95) for calprotectin, 0.72 (0.60–0.85) for FE Na , and 0.89 (0.81–0.96) for protein-to-creatinine ratio. Conclusion In this study, urinary [TIMP-2]•[IGFBP7] was inferior to urinary calprotectin, FE Na and proteinuria in differentiating functional from intrinsic AKI. Impact Acute kidney injury (AKI) affects up to 48% of critically ill neonates and children and is independently associated with increased morbidity and mortality. Differentiating functional from intrinsic AKI is essential due to distinct treatment strategies, yet reliable laboratory biomarkers remain scarce. This study evaluated urinary TIMP-2 and IGFBP7 for diagnostic accuracy in AKI differentiation to improve patient outcome. While urinary [TIMP-2]•[IGFBP7] effectively diagnosed AKI, its differential diagnostic accuracy was moderate. Calprotectin, fractional excretion of sodium, and protein-to-creatinine ratio showed superior discriminatory ability. Our findings contribute important evidence on biomarker use and limitations in the vulnerable neonatal and pediatric population.