The combination of mRAI with [TIMP-2]×[IGFBP7] yields the highest absolute predictive performance (AUC 0.82, 95% CI 0.72-0.93).<h4>Conclusions</h4>Sequential risk stratification combining clinical RAIs with targeted urinary biomarkers profiling significantly improves early prediction of severe AKI in critically ill adults' patients. Here, IGFBP7 is linked to acute kidney injury.