Hemodialysis Membrane With a High-Molecular-Weight Cutoff and Cytokine Levels in Sepsis Complicated by Acute Renal Failure: A Phase 1 Randomized Trial

Background

Sepsis 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 Design

Double-blind, crossover, randomized, controlled, phase 1 trial.

Setting & Participants

Tertiary intensive care unit. 10 septic patients with acute renal failure according to RIFLE class F.

Intervention

Each patient was treated with 4 hours of high-cutoff (HCO)-IHD and 4 hours of high-flux (HF)-IHD.

Outcomes & Measurements

We 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.

Results

Median 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).

Limitations

Small phase 1 trial.

Conclusion

In 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.