In recent decades, clinical research on early biomarkers of renal injury has been frequent and intensive, with proenkephalin (PENK) being indicated as a promising filtration biomarker (BM). From a cohort of 57 patients, blood samples were collected preoperatively and 48 h after liver transplantation (LT). The following BMs were analyzed: PENK, cystatin-C (CYS-C), and serum creatinine (Scr). Diagnosis of AKI was based on the KDIGO criteria. Of the 57 patients undergoing LT, 50 (88%) developed acute kidney injury (AKI) and were categorized as follows: no-AKI/mild-AKI - 21 (36.8%) and severe-AKI 36 (63.2%). During the preoperative period, only PENK was significantly higher in patients with severe AKI, with an AUC of 0.69 (CI 0.54-0.83), a cutoff of 55.30 pmol/l, a sensitivity of 0.86, a specificity of 0.52, and an accuracy of 0.75. In addition, subclinical AKI was determined preoperatively in 32 patients. Forty-eight hours after LT, PENK maintained its performance in determining severe AKI, with an AUC of 0.83 (CI 0.72-0.94), a cutoff of 119.05 pmol/l, a sensitivity of 0.81, a specificity of 0.90, and an accuracy of 0.84. PENK detected AKI 48 h earlier than serum creatinine. In a multivariate linear regression analysis, PENK was an independent predictor of severe AKI. This small study suggests that the filtration biomarker PENK shows promise for detecting AKI in patients undergoing LT, revealing greater accuracy and an earlier rise in patients with severe AKI. The combination of kidney functional and filtration BMs may aid in the management and prevention of AKI progression.