Abstract Background and Aims The diagnosis of AKI, according to the KDIGO guidelines, is still based on a tangible increase in serum creatinine which, however, cannot be detected until 24-48 hours after renal damage. Unfortunately, it has not been possible to identify among the various new biomarkers the one that is potentially able to detect AKI early, to intervene promptly to preserve renal function. The aim of this study was to analyze, in a population of patients undergoing major non-cardiac surgery, the most recent urinary biomarkers to evaluate their predictive potential for AKI and compare them with creatinine levels. Method 22 patients (18 males, 4 females) with an average age of 76 (67-85) years were enrolled for the study. 22 urine samples were analyzed by: Results Carrying out a correlation between the new biomarkers for AKI (Nephrocheck, NGALds and SEPP1) with creatinine levels at different times (pre-operative, post-operative and 24 h post-operative) shows a significant correlation only with NGALds (respectively p = 0.017, p = 0.035 and p = 0.012) (Table). Subdividing patients based on the increase in creatinine levels from pre-operation to 24 hours post-operation, the only biomarker that showed an increase in values was NGALds, while the others showed levels discordant with creatinine. Conclusion By analyzing the new biomarkers and comparing them with the creatinine data, it emerged that NGALds alone significantly correlated with the latter at different times. The other urinary biomarkers (Nephrocheck and SEPP1) showed no correlation with creatinine levels. Based on this outcome, it could be assumed that NGALds is the biomarker which, due to its characteristics already stated in numerous studies and its correlation with creatinine, could be used and replace the latter as an early biomarker of AKI.