Mean airway pressure as an independent risk factor for developing acute kidney injury in mechanically ventilated critically ill patients: a multi-center retrospective analysis.

Mechanical ventilation is a well-recognized risk factor for acute kidney injury (AKI), but the specific role of mean airway pressure (P_mean) remains insufficiently defined. We conducted a multicenter retrospective cohort study including 17,428 mechanically ventilated patients from the MIMIC-IV and eICU-CRD databases. To evaluate the association between P_mean within the first 24 h of ventilation and subsequent AKI, we applied machine learning-based feature selection, multivariable regression, propensity score matching (PSM), and subgroup analyses. Across all analytical approaches, P_mean consistently emerged as the most influential ventilatory parameter associated with AKI. A non-linear dose-response relationship was observed, with threshold effects at approximately 8.8 cmH₂O in the MIMIC-IV cohort and 10.0 cmH₂O in the eICU-CRD cohort. Beyond these inflection points, each 1-cmH₂O increase in P_mean was associated with significantly higher risks of AKI and adverse outcomes, including mortality and the need for renal replacement therapy. These associations remained robust across regression models, PSM, and multiple subgroup analyses. Collectively, our findings indicate that elevated P_mean is independently associated with AKI risk in critically ill patients receiving mechanical ventilation. The identification of clinically relevant inflection points provides a pragmatic exposure definition that may inform risk stratification and the design of future prospective and randomized studies evaluating kidney-conscious ventilatory strategies.