Objective:To investigate the predictive value of serum proenkephalin A 119-159 (penKid) on incidence and the 28-day mortality in patients with sepsis-associated acute kidney injury (SA-AKI).Methods:This study was a single center, observational cohort study. Sepsis/septic shock patients admitted to Department of Critical Care Medicine of Taizhou People's Hospital Affiliated to Nanjing Medical University from September 2021 to September 2022 were selected and divided into the SA-AKI group and the non-SA-AKI group according to whether acute kidney injury (AKI) occurred within 28 days. Patients in the SA-AKI group were subdivided into the death group and the survival group according to whether death occurred within 28 days. Baseline data and laboratory indicators such as penKid concentration were compared among different groups. COX regression analysis was used to explore the risk factors of death within 28 days in the SA-AKI patients, And Kaplan-Meier curve was used to analyze patient prognosis.Result:A total of 161 patients were included in this study, of whom 66 (41.0%) developed AKI. The baseline penKid concentration in the SA-AKI group was significantly higher than that in the non-SA-AKI group [(2.99 ± 0.68) μg/L vs. (1.86±0.75) μg/L, P<0.05]. Multivariate COX regression analysis showed that the baseline penKid ( HR=5.608, 95% CI: 3.507-8.967, P<0.001) and lactate (LA) ( HR=1.089, 95% CI: 1.003-1.183, P=0.043) were independent risk factors for AKI in sepsis/septic shock patients. Of the 66 SA-AKI patients, 27 (40.9%) died within 28 days, and the baseline penKid concentration in the death group was significantly higher than that in the survival group [ (3.55 ± 0.54) μg/L vs. (2.60±0.47) μg/L, P<0.05]. COX regression analysis showed that penKid ( HR=5.892, 95% CI: 2.457-14.132, P<0.001) was an independent risk factor for mortality in SA-AKI patients. Kaplan-Meier curve showed that the 28-day mortality of patients with baseline penKid ≥ 3.24 μg/L was significantly higher than that of patients with baseline penKid <3.24 μg/L ( P<0.001). Conclusions:In sepsis/septic shock patients, the penKid concentration measured on the first day in the SA-AKI group is significantly higher than that in the non-SA-AKI group. In SA-AKI patients, the penKid concentration measured in patients who survived within 28 days is significantly lower than that in the death group. PenKid is an independent risk factor for the occurrence and death of SA-AKI.