Mechanical ventilation–associated AKI: toward a multimodal and kidney-protective ventilatory framework

Abstract Mechanical ventilation–associated acute kidney injury (AKI) represents a complex manifestation of lung–kidney cross-talk driven by hemodynamic alterations, neurohumoral activation, systemic inflammation and disturbances in gas exchange and acid–base homeostasis. Beyond static ventilatory settings, increasing evidence suggests that dynamic fluctuations in airway and perfusion parameters, including static driving pressure (ΔP), positive end-expiratory pressure (PEEP), mean airway pressure (P mean ), and effective renal perfusion pressure (eRPP) may substantially influence renal vulnerability during mechanical ventilation. This comprehensive narrative review synthesizes current mechanistic and clinical evidence on the relationship between mechanical ventilation and AKI and proposes an integrated framework for future research on the interplay between ventilatory stress, venous congestion, renal perfusion, and inflammatory injury. Emerging bedside tools such as renal Doppler indices, venous excess ultrasound score (VExUS), and kidney injury biomarkers are discussed as components of an integrated physiologic approach for early recognition and risk stratification of ventilator-associated AKI. We further propose a multimodal conceptual framework integrating respiratory mechanics, congestion assessment, perfusion monitoring, and biomarkers to support individualized kidney-protective ventilation strategies. Future research should prioritize standardized physiologic monitoring, time-varying exposure analyses, causal mediation approaches, and prospective multicenter studies to better define renal-protective ventilatory targets and advance precision critical care.