• Michael Haase, Rinaldo Bellomo, Ian Baldwin, Anja Haase-Fielitz, Nigel Fealy, Piers Davenport, Stanislao Morgera, Hermann Goehl, Markus Storr, Neil Boyce, and Hans-Hellmut Neumayer.
• Intensive Care Unit, Austin Hospital, University of Melbourne, Australia.
• Am. J. Kidney Dis. 2007 Aug 1; 50 (2): 296-304.

BackgroundSepsis is the leading cause of acute renal failure. Intermittent hemodialysis (IHD) is a common treatment for patients with acute renal failure. However, standard hemodialysis membranes achieve only little diffusive removal of circulating cytokines. Modified membranes may enable both successful IHD treatment and simultaneous diffusive cytokine removal.Study DesignDouble-blind, crossover, randomized, controlled, phase 1 trial.Setting & ParticipantsTertiary intensive care unit. 10 septic patients with acute renal failure according to RIFLE class F.InterventionEach patient was treated with 4 hours of high-cutoff (HCO)-IHD and 4 hours of high-flux (HF)-IHD.Outcomes & MeasurementsWe chose relative change in plasma interleukin 6 (IL-6) concentrations from baseline to 4 hours as the primary outcome for effective cytokine removal. We measured plasma and effluent concentrations of cytokines (IL-6, IL-8, IL-10, and IL-18) and albumin.ResultsMedian age was 53 years (25(th) to 75(th) percentiles, 43 to 71 years). Both treatments achieved equal control of uremia. Four hours of HCO-IHD accomplished a greater decrease in plasma IL-6 levels (-30.3%) than 4 hours of HF-IHD (1.1%; P = 0.05). HCO-IHD, but not HF-IHD, achieved substantial diffusive clearance of several cytokines (IL-6, 14.1 mL/min; IL-8, 75.2 mL/min; and IL-10, 25.5 mL/min). Such clearance also was associated with greater relative decreases in plasma IL-8 and IL-10 levels in favor of HCO-IHD (P = 0.02, P = 0.04). We found significantly greater relative changes from prefilter to postfilter plasma IL-6, IL-8, and IL-10 values in favor of HCO-IHD (P = 0.02, P = 0.01, P < 0.01). During HCO-IHD, cumulative albumin loss into the effluent was 7.7 g (25(th) to 75(th) percentiles, 4.8 to 19.6) versus less than 1.0 g for HF-IHD (P < 0.01).LimitationsSmall phase 1 trial.ConclusionIn septic patients with acute renal failure, HCO-IHD achieved simultaneous uremic control and diffusive cytokine clearances and a greater relative decrease in plasma cytokine concentrations than standard HF-IHD.

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