Acute kidney injury with hydroxyethyl starch 130/0.42 in severe sepsis

BACKGROUND: We aimed to detail the effects of hydroxyethyl starch (HES) vs. Ringer's on kidney function including the interaction with mortality in post-hoc analyses as resuscitation with HES 130/0.42 increased mortality in the Scandinavian Starch for Severe Sepsis/Septic Shock (6S) trial. METHODS: In all 798 randomised patients, we assessed the incidence and effect on mortality of acute kidney injury (AKI) in the HES vs. Ringer's acetate groups using the Kidney Disease: Improving Global Outcome criteria. We also assessed the intervention effect on time to and duration of renal replacement therapy (RRT). RESULTS: At baseline, the intervention groups were similar. The maximal AKI stage was higher in the HES vs. Ringer's group within the first 5 days after randomisation (P = 0.03), the average difference being 0.2 points (P < 0.01). An increase in AKI stage was associated with mortality (hazard ratio (HR) 1.35; 95% CI 1.22 to 1.49; P < 0.01). Significantly, more patients in the HES group received RRT within the first 5 days (P = 0.01), and the time to initiation of RRT was also shorter compared with the Ringer's group (HR 1.40; 95% CI 1.01-1.93; P = 0.04). The intervention effect of HES on mortality was reduced when adjusting for AKI stage as a time-dependent covariate (P = 0.15). CONCLUSION: In patients with severe sepsis, HES appeared to increase the rate of severe AKI and use of RRT within the first 5 days. The increased mortality observed with HES may have been partly mediated through acute kidney impairment.