Acute kidney injury in septic shock: clinical outcomes and impact of duration of hypotension prior to initiation of antimicrobial therapy

To describe the incidence and outcomes associated with early acute kidney injury (AKI) in septic shock and explore the association between duration from hypotension onset to effective antimicrobial therapy and AKI. Retrospective cohort study. A total of 4,532 adult patients with septic shock from 1989 to 2005. Intensive care units of 22 academic and community hospitals in Canada, the United States and Saudi Arabia. In total, 64.4% of patients with septic shock developed early AKI (i.e., within 24 h after onset of hypotension). By RIFLE criteria, 16.3% had risk, 29.4% had injury and 18.7% had failure. AKI patients were older, more likely female, with more co-morbid disease and greater severity of illness. Of 3,373 patients (74.4%) with hypotension prior to receiving effective antimicrobial therapy, the median (IQR) time from hypotension onset to antimicrobial therapy was 5.5 h (2.0-13.3). Patients with AKI were more likely to have longer delays to receiving antimicrobial therapy compared to those with no AKI [6.0 (2.3-15.3) h for AKI vs. 4.3 (1.5-10.8) h for no AKI, P < 0.0001). A longer duration to antimicrobial therapy was also associated an increase in odds of AKI [odds ratio (OR) 1.14, 95% CI 1.10-1.20, P < 0.001, per hour (log-transformed) delay]. AKI was associated with significantly higher odds of death in both ICU (OR 1.73, 95% CI 1.60-1.9, P < 0.0001) and hospital (OR 1.62, 95% CI, 1.5-1.7, P < 0.0001). By Cox proportional hazards analysis, including propensity score-adjustment, each RIFLE category was independently associated with a greater hazard ratio for death (risk 1.31; injury 1.45; failure 1.56). Early AKI is common in septic shock. Delays to appropriate antimicrobial therapy may contribute to significant increases in the incidence of AKI. Survival was considerably lower for septic shock associated with early AKI, with increasing severity of AKI, and with increasing delays to appropriate antimicrobial therapy.