<b><i>Background/Aims:</i></b> Early initiation of renal replacement therapy (RRT) is recommended in order to improve the clinical outcome of patients who develop an acute kidney injury (AKI). However, markers that guide an early RRT initiation do not really exist currently. <b><i>Methods:</i></b> Urine and serum samples were prospectively collected from 120 AKI patients. Depending on the necessity of initiating RRT, patients were divided into 2 different groups: dialysis (n = 52) and non-dialysis (n = 68). <b><i>Results:</i></b> Comparative urinary proteomic analyses identified 4 different proteins (fatty acid binding proteins 1 and 3 (FABP1 and FABP3), β-2-microglobulin (B2M), cystatin-M (CST6)) that discriminate AKI patients with high risk for RRT. Western blot analysis confirmed the proteomics data for FABP1 and FABP3 but not for B2M and CST6. Validation analysis confirmed that the FABP1 and FABP3 fulfilled the requirement of functioning as markers for AKI patients with risk to dialysis (p < 0.001). <b><i>Conclusion:</i></b> The release of high amounts of FABP1 and FABP3 in urine of AKI patients could serve as a diagnostic/prognosis marker for RRT initiation in these patients.