Plasma exosomal microRNAs as early predictors of subclinical acute kidney injury in septic patients undergoing major non-cardiac surgery: a prospective observational cohort study

Early identification of acute kidney injury (AKI), including subclinical AKI, remains a critical challenge in septic patients undergoing major non-cardiac surgery. Exosomal microRNAs (miRNAs) represent emerging biomarkers capable of reflecting early renal cellular stress before detectable changes in serum creatinine occur. This prospective observational cohort study enrolled 120 adult septic patients undergoing major non-cardiac surgery (> 2 h) at Imam Sajjad Hospital, Tabriz, between early 2025 and August 2025 (Ethics Approval ID: IR.IAU.TABRIZ.REC.1404.179). Peripheral blood was obtained at three perioperative time points (preoperative, intraoperative, and 24 h postoperative) for exosome isolation and miRNA quantification. Clinical AKI was defined according to KDIGO criteria. Subclinical AKI was defined as urinary TIMP-2 × IGFBP7 > 0.3 in the absence of any rise in serum creatinine. Diagnostic performance of candidate miRNAs was assessed using receiver operating characteristic (ROC) analysis based on observed patient data. Among the 120 enrolled patients, a proportion developed AKI during the 24-hour postoperative observation period (final numbers provided in the Results section). Patients who developed AKI demonstrated distinct perioperative alterations in specific exosomal miRNAs compared with those who did not develop AKI. Several miRNAs showed measurable discriminatory ability for early AKI detection across different sampling time points, with areas under the ROC curve (AUCs) ranging within clinically relevant thresholds (AUC values reported in the Results and Tables following recalculation using observed data with 95% confidence intervals). These findings suggest that perioperative plasma exosomal miRNAs may serve as promising early indicators of acute kidney injury in septic patients undergoing major surgery. Their potential role in identifying subclinical AKI warrants further investigation in studies specifically powered for this endpoint.