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However, whether this association is direct or mediated by intraoperative hypotension (IOH) is unclear. We hypothesized that IOH mediates the relationship between preoperative comorbidities and postoperative AKI.Methods: Data from adult patients undergoing non-cardiac surgery under general anesthesia were analyzed. Inverse probability of treatment weighting (IPTW) was applied to achieve a balance between the exposure groups by reducing the baseline differences in the measured covariates. Structural equation modeling (SEM)-based mediation analysis was conducted using the American Society of Anesthesiologists physical status (ASA-PS) classification \u2265 3 as an input and postoperative AKI as an outcome. IOH (duration of mean arterial pressure &lt; 60 mmHg), along with albumin and hemoglobin levels, was considered a mediator. We also performed interaction analysis between patient sex and age.Results: After IPTW, 8643.9 (10.8%) patients had an ASA-PS of \u2265 3. AKI occurred more frequently (4.5% vs. 6.9%, P &lt; 0.001) in patients with ASA-PS \u2265 3. ASA-PS \u2265 3 was associated with a total effect estimate of 0.02 on the log-odds of postoperative AKI (P &lt; 0.001). Of the total effect of ASA-PS \u2265 3 on postoperative AKI, 48% was significantly mediated by IOH (26%) and hypoalbuminemia (26%), though anemia showed no significance. The effect of high ASA-PS scores on postoperative AKI was significantly modified by sex, but not by age.Conclusions: High ASA-PS scores increase AKI risk after non-cardiac surgery, a relationship partially mediated by statistically significant pathways involving IOH and hypoalbuminemia.<\/jats:p>","DOI":"10.4097\/kja.25765","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T02:09:58Z","timestamp":1771466998000},"page":"426-433","update-policy":"https:\/\/doi.org\/10.4097\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The impact of preoperative comorbidity and intraoperative hypotension on postoperative acute kidney injury after non-cardiac surgery: a structural equation modeling-based mediation 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