Abstract

OBJECTIVES: Although preclinical evidence indicates that injurious mechanical ventilation may lead to acute kidney injury (AKI), relevant clinical evidence is limited. We aimed to investigate the association of driving pressure (a marker of injurious mechanical ventilation) with subsequent development of AKI in patients with acute respiratory distress syndrome (ARDS). DESIGN: Secondary analysis of individual patient-level data from seven ARDS Network and Prevention and Early Treatment of Acute Lung Injury (PETAL) Network randomized controlled clinical trials. SETTING: Adult ICUs participating in the ARDS Network and PETAL Network trials. PATIENTS: After exclusion of patients with early AKI (i.e., those who met AKI criteria within the first 2 d following ARDS onset), we classified the study population into two groups: "late AKI" and "no AKI." The "late AKI" group included patients who developed AKI more than 2 days but no longer than 7 days following ARDS onset. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 5367 patients with ARDS initially enrolled in trials, 2960 patients were included in the main analysis. Late AKI developed in 1000 patients (33.8%). After controlling for confounders, baseline driving pressure was independently associated with development of late AKI (each 1 sd increase in driving pressure was associated with a 35% increase in the odds of late AKI [odds ratio, 1.35; 95% CI, 1.15-1.58]). This result persisted in the sensitivity analysis, which did not exclude patients with early AKI, and in the sensitivity analysis, which included patients who developed AKI later than 7 days following ARDS onset. There was a threshold of driving pressure equal to 15 cm H 2 O for its association with development of late AKI. CONCLUSIONS: Driving pressure was associated with subsequent development of AKI in patients with ARDS suggesting that injurious mechanical ventilation may lead to AKI.