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The current study aimed to investigate whether prognostic nutritional index (PNI) is an independent predictor of acute kidney injury (AKI) and mortality of patients in the coronary care unit (CCU). In the present two-stage observational study of patients in the CCU, 6,444 patients from the Medical Information Mart for Intensive Care (MIMIC) III database were first enrolled (test cohort), after which 412 patients from Zhongnan Hospital of Wuhan University were recruited in the validation cohort. AKI was defined based on the Kidney Disease Improving Global Outcomes AKI criteria. The primary endpoint was the incidence of AKI stratified by severity, while the second endpoint included in-hospital mortality and 2-year mortality. In the test cohort, 4,457 (69.2%) patients developed AKI during hospitalization. Following multivariable adjustment, the highest quartile of the PNI value was associated with a 1.8-fold increased risk of AKI compared with the lowest quartile. For the prediction of AKI, the area under the receiver operating characteristic curve outperformed the acute physiology score III score and clinical model in patients with or without preexisting chronic kidney disease, and this was further validated in the hospital cohort used in the present study. A total of 2,219 patients suffered mortality during the 2-year follow-up, and PNI was indicated to independently predict the risk of in-hospital mortality and 2-year mortality in the test cohort and in the validation cohort. Decision curve analysis indicated that the PNI values were clinically useful; Therefore, the current study demonstrated that the PNI value is an independent predictor of AKI and mortality in patients within the CCU. [ABSTRACT FROM AUTHOR]