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TNF-alpha elimination with high cut-off haemofilters: a feasible clinical modality for septic patients?

BACKGROUND
Renal replacement therapies with high cut-off haemofilters are new approaches in the adjuvant therapy of sepsis. We analysed the cytokine elimination capacity of a newly developed polyflux high cut-off haemofilter. Different renal replacement therapies are compared and tested for their clinical feasibility.


METHODS
Blood from healthy volunteers (n=15) was incubated for 4 h with 1 mg of endotoxin and then circulated through a closed extracorporeal circuit. A newly developed polyflux haemofilter (P2SX) was used. Haemofiltration, haemodialysis and albumin dialysis were tested. IL-1ra (17 kDa), interleukin-6 (IL-6) (28 kDa), tumour necrosis factor alpha (TNF-alpha) (51 kDa), albumin (64 kDa), creatinkinase (CK) (80 kDa) and IgG (140 kDa) were measured in blood and filtrates prior to the initiation and after 5 min, 1, 2 and 4 h.


RESULTS
Haemofiltration was superior to haemodialysis in the clearance capacity of all substances when applied in the 1 l/h ultrafiltration mode. Increasing the ultrafiltration rate/dialysate flow from 1 to 3 l/h led to a significant increase in cytokine clearances (P<0.001). At 3 l/h the differences between haemofiltration and haemodialysis vanished and both techniques achieved comparable cytokine clearances. Median clearance values ranged between 25 and 54 ml/min for interleukin-1 receptor antagonist (IL-1ra), 23 and 42 ml/min for IL-6 and 15 and 28 ml/min for TNF-alpha. Albumin loss was highest in the haemofiltration group with albumin clearances ranging between 7 and 13 ml/min. Using diffusion instead of convection significantly reduced the loss of albumin (P<0.01 for 1 l/h, P<0.05 for 3 l/h). Albumin dialysis was able to completely inhibit albumin loss but cytokine clearance capacity was limited.


CONCLUSIONS
High cut-off haemofilters achieve high clearances for inflammatory IL-6 and TNF-alpha. Due to the high protein loss in haemofiltration, dialysis in combination with balanced protein substitution seems to be a suitable approach for clinical trials.