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

• Published in: Nephrology, dialysis, transplantation Vol. 18; no. 7; pp. 1361 - 1369
• Main Authors: Morgera, Stanislao, Klonower, Daniela, Rocktäschel, Jens, Haase, Michael, Priem, Friedrich, Ziemer, Sabine, Wegner, Brigitte, Göhl, Hermann, Neumayer, Hans‐H.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.07.2003
• Subjects: Acute Kidney Injury - etiology; Acute Kidney Injury - therapy; Acute Kidney Injury - urine; Adult; albumin dialysis; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antineoplastic Agents - urine; Biological and medical sciences; Cytokines - urine; Emergency and intensive care: infection, septic shock; Emergency and intensive care: renal failure. Dialysis management; Equipment Design; Feasibility Studies; haemodialysis; haemofiltration; Hemofiltration - instrumentation; high cut‐off haemofilter; Humans; In Vitro Techniques; Intensive care medicine; Interleukin-6 - urine; Medical sciences; Reference Values; Renal Dialysis - instrumentation; Sepsis - complications; Sepsis - therapy; Sepsis - urine; Time Factors; TNF‐α elimination; Tumor Necrosis Factor-alpha - urine; Human; albumin dialysis; Hemodialysis; Cytokine; haemodialysis; Infection; Sepsis syndrome; Extrarenal dialysis; Treatment; Tumor necrosis factor; TNF-α elimination; Application method; high cut-off haemofilter; Technique; haemofiltration
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfg115

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‐α) (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‐α. 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‐α. Due to the high protein loss in haemofiltration, dialysis in combination with balanced protein substitution seems to be a suitable approach for clinical trials.