Acute kidney injury (AKI) is a common complication of critical illness, and the mortality rate of AKI in the intensive care unit (ICU) is 30-50%. Recent studies have demonstrated that mechanical ventilation (MV) contributes to the development of AKI, yet few studies have investigated the impact of AKI during MV on ICU outcomes. We performed a retrospective analysis of a large ICU cohort to investigate the hypothesis that AKI would lead to increased duration of MV, length of ICU stay, and mortality. METHODS: Medical records of all patients admitted to the University of California, San Diego (UCSD) ICU between January 1, 2014 and November, 30 2016 were screened. Patients with ESRD were excluded, and those with AKI were identified based on KDIGO criteria. Outcomes were evaluated in 6 groups; 1) No MV or AKI, 2) No MV+AKI, 3) MV with no AKI, 4) AKI at initiation of MV, 5) AKI during MV, and 6) AKI post-MV. After tests for normality, differences in continuous, categorial and independent proportions were compared using two tailed Ttest or Mann Whitney U; Fisher's exact test; and Z-test respectively at a 0.05 level of significance. Kaplan-Meier time to event analysis was used to plot trends in ICU survival among the groups. RESULTS: 9704 patients were included in our analysis, and 4275 patients had AKI. The incidence of AKI in patients not treated with MV was 32% vs 58% in those who were (p-value :<0.001). Total days with AKI and need for CRRT were increased in groups who had AKI while on MV compared to the No MV+AKI (23.6% vs 0.6%, p and 16.3% vs 0.6, p) and AKI post-MV (23.6% vs 1.9%, p< 0.001 and 16.3% vs 1.9, p< 0.001) groups. Patients in the AKI at the initiation of MV and AKI during MV groups required significantly longer durations of ventilation days (4[2-8] vs. 2[2-3], p < 0.001; and 6[3 -12] vs. 2[2-3], p < 0.001); and lengthier ICU stays (12 [8-20] vs 4[3-6], p <0.001; and 9[5-17] vs 4[3-6], p <0.001) compared to MV patients without AKI. Mortality was also significantly increased in the MV+AKI groups (28.4% vs 6.2%, p <0.001 and 21.5% vs 6.2%, p<0.001). CONCLUSIONS: MV was associated with higher rates of AKI. AKI during MV prolongs MV duration and significantly increases mortality. This study highlights the need for mechanistic studies focused on ventilator-kidney interactions that may lead to novel preventative strategies.