Background: Changes in mean perfusion pressure (MPP) from premorbid resting values may contribute to the progression of septic acute kidney injury (AKI). Objectives: In patients with septic shock, we aimed to investigate the association of changes from premorbid values with AKI severity and progression. Methods: We obtained premorbid resting mean arterial pressure (MAP), central venous pressure (CVP), and MPP, and then recorded data from intensive care unit admission 2 hourly for the first 24 hours to calculate hemodynamic deficits. We recorded 4-hourly creatinine measurements for 96 hours. The association of hemodynamic variables with progression of AKI by Kidney Disease: Improving Global Outcomes =. 2 stages was explored by multivariate logistic regression. Results: Of 107 patients, 55 (51.4 ) had severe AKI. Median MAP deficit was similar for patients with or without severe AKI. Median MPP deficit was 29 in patients with severe AKI and 24 in those without (P = 04), a difference determined by greater CVP levels. Central venous pressure was independently associated with worsening AKI (odds ratio, 1.26 [95 confidence interval, 1.01-1.58]; P = .04). Conclusions: Mean arterial pressure and MPP deficits were substantial in septic shock patients, with patients with severe AKI having a greater MPP deficit. However, only CVP was independently associated with AKI progression. These findings suggest a possible role for venous congestion in septic AKI.