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. This evidence concerns the gene TIMP2 and acute kidney injury.