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.


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


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


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


METHODS
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).


CONCLUSIONS
Small phase 1 trial.


CONCLUSIONS
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.
Haase
Michael
M
Intensive Care Unit, Austin Hospital, University of Melbourne, Australia.
Bellomo
Rinaldo
R
Baldwin
Ian
I
Haase-Fielitz
Anja
A
Fealy
Nigel
N
Davenport
Piers
P
Morgera
Stanislao
S
Goehl
Hermann
H
Storr
Markus
M
Boyce
Neil
N
Neumayer
Hans-Hellmut
HH
D058186:Acute Kidney Injury / Q000097:blood* / Q000209:etiology / Q000628:therapy; D000328:Adult; D000368:Aged; D018592:Cross-Over Studies; D016207:Cytokines / Q000097:blood*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008567:Membranes, Artificial; D008875:Middle Aged; D006435:Renal Dialysis / Q000295:instrumentation* / Q000592:standards; D018805:Sepsis / Q000097:blood* / Q000150:complications / Q000628:therapy
D016207:Cytokines; D008567:Membranes, Artificial