Nephrol Dial Transplant (2002) 17: 1957-1963
© 2002 European Renal Association-European Dialysis and Transplant Association
In vitro studies on hirudin elimination by haemofiltration: comparison of three high-flux membranes
1 Department of Nephrology and Clinical Immunology, University Hospital Aachen and 2 Department of Nephrology, Klinikum Braunschweig, Braunschweig, Germany
Background. Recombinant hirudin (r-hirudin) is a highly selective thrombin inhibitor used for anticoagulation in heparin-induced thrombocytopenia type II. R-hirudin is increasingly applied to patients with renal failure and on renal replacement therapy. Since kidney function impairment strongly prolongs r-hirudin elimination half-life, severe accumulation and bleeding complications may occur. Data on the r-hirudin permeability and elimination capacity of different haemofilters are limited.
Methods. Three haemofilter types were investigated: high-flux polysulphone (Fresenius), AN69 (Hospal), and polyamide (Gambro). We used two in vitro haemofiltration models: (i) an open post-dilution haemofiltration model with ultrafiltration and fluid substitution (model 1) simulating hirudin intoxication, and (ii) a closed model with ultrafiltrate reinfusion (model 2) to determine steady-state sieving coefficients (SC). Fresh human heparinized blood (2 IU unfractionated heparin/ml blood) was used. In model 2, SC obtained with human whole blood were compared with isotonic saline.
Results. In model 1, r-hirudin levels decreased significantly faster with polysulphone than with AN69 or polyamide (P<0.05). In accordance with this, in model 2 the observed SC in whole blood were 1.11±0.28 (polysulphone), 0.61±0.15 (AN69) and 0.33±0.13 (polyamide), and clearances were 28±7 (polysulphone), 15±4 (AN69) and 8±3 ml/min (polyamide) (P<0.001 for all comparisons). The SC in saline were slightly but significantly lower for polysulphone (0.88±0.12), similar for AN69 (0.59±0.1), and significantly improved for polyamide (0.83±0.1).
Conclusions. Elimination of r-hirudin by haemofiltration strongly depended on the membrane material. Using human blood, we observed large differences between the three high-flux membranes. The saline experiments suggest a membrane-dependent impact of plasma proteins and pH on hirudin sieving. Our findings have implications for r-hirudin dosage in haemofiltration, for treatment of overdosage, and for future in vitro haemofiltration studies.
Keywords: elimination; haemofiltration; hirudin; in vitro study; overdosage; sieving coefficient
Correspondence and offprint requests to: R. D. Frank, MD, Department of Nephrology, University Hospital Aachen, 52057 Aachen, Germany. Email: dario.frank{at}ukaachen.de
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