Nephrol Dial Transplant (2003) 18: 1361-1369
© 2003 European Renal Association-European Dialysis and Transplant Association
TNF-
elimination with high cut-off haemofilters: a feasible clinical modality for septic patients?
1 Department of Nephrology, CharitéHumboldt University of Berlin, 2 Laboratory Medicine and Pathobiochemistry, CharitéHumboldt University of Berlin, 3 Institute for Medical Biometrics, CharitéHumboldt University of Berlin and 4 Gambro Corporate Research, Hechingen, Germany
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-
) (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-. 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-. Due to the high protein loss in haemofiltration, dialysis in combination with balanced protein substitution seems to be a suitable approach for clinical trials.
Keywords: albumin dialysis; haemodialysis; haemofiltration; high cut-off haemofilter; TNF- elimination
Correspondence and offprint requests to: Dr Stanislao Morgera, Universitätsklinikum Charité der Humboldt Universität zu Berlin, Medizinische Klinik mit Schwerpunkt Nephrologie am CCM, Schumannstrasse 20–21, D-10098 Berlin, Germany. Email: stanislao.morgera{at}charite.de
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