Ventilator-Associated Pneumonia: The Role of Kidney-Lung Crosstalk and Renal Replacement Therapy, a Narrative Review.

Background/Objectives: Multiple organ dysfunction syndrome (MODS) results from dynamic inter-organ interactions rather than isolated organ failures. Among these, kidney-lung crosstalk is a key determinant of outcomes in critically ill patients. Acute kidney injury (AKI) promotes pulmonary dysfunction through hemodynamic, inflammatory, endothelial, and metabolic mechanisms, while acute respiratory failure and mechanical ventilation may aggravate renal injury. Ventilator-associated pneumonia (VAP) may represent a clinical consequence of these interactions, although causality remains uncertain. Renal replacement therapy (RRT) may further influence kidney-lung crosstalk through several physiological mechanisms. To summarize current evidence on kidney-lung crosstalk, evaluate its potential contribution to VAP susceptibility, and examine the role of RRT in modulating these interactions. Methods: Narrative review of experimental, translational, and clinical studies investigating bidirectional kidney-lung interactions in critical illness. Results: Kidney-to-lung crosstalk involves fluid overload, venous congestion, immune activation, endothelial dysfunction, and metabolic disturbances. Lung-to-kidney signaling is driven by mechanical ventilation, ventilator-induced lung injury, hypoxemia, and hypercapnia. Clinical evidence is strongest for fluid overload, venous congestion, and mechanical ventilation, whereas endothelial dysfunction and uremic toxins remain supported mainly by experimental data. AKI-associated immune dysfunction and prolonged mechanical ventilation provide biologically plausible mechanisms linking AKI to VAP, but definitive causal evidence is lacking because of methodological limitations. RRT may influence these interactions through optimized fluid balance, correction of acid-base disorders, improved antimicrobial pharmacokinetics, and potentially extracorporeal immunomodulation. However, no randomized trial has demonstrated a direct reduction in VAP incidence attributable to RRT. Conclusions: Kidney-lung crosstalk is a major driver of organ dysfunction in critical illness, yet translation into targeted therapies remains limited. Current evidence supports integrated organ-protective strategies-including lung-protective ventilation, individualized fluid management, VAP prevention, and optimized antimicrobial therapy-while future advances will rely on biological phenotyping, biomarker-guided risk stratification, and robust causal inference approaches.