Comparative analysis of procoagulatory activity of haemodialysis, haemofiltration and haemodiafiltration with a polysulfone membrane (APS) and with different modes of enoxaparin anticoagulation

Effect of membrane composition and structure on solute removal and biocompatibility in hemodialysis. Significant changes in extracorporeal membranes have occurred over the past five decades in which hemodialysis (HD) has been available as a therapy for both acute renal failure (ARF) and end-stage renal disease (ESRD). For cellulosic membranes, these changes have included a reduction in thickness, hydroxyl group substitution, and an increase in pore size. These modifications have resulted in enhanced efficiency of small solute removal, a broader spectrum of overall solute removal, and an attenuation of complement activation in comparison to the thick, unsubstituted cellulosic membranes of low permeability used in the early days of HD therapy. Synthetic membranes, originally developed specifically for use in high-flux HD and hemofiltration, have also evolved during this same time period. In fact, the initially clear distinction between low-flux regenerated cellulosic and high-flux synthetic membranes has become blurred, as membrane formulators have developed products designed to appeal to enthusiasts for both membrane formats. The purpose of this review is to characterize both the solute removal and biocompatibility characteristics of dialysis membranes according to their composition (that is, polymeric makeup) and structure. In this regard, the manner in which membrane biocompatibility interacts with flux is highlighted.

A single bolus dose of LMW heparin at the start of haemodialysis effectively prevents clot formation in the dialyser and bubble trap. However, there are few studies on the appropriate dosage of LMW heparins in haemodialysis. Therefore we examined the relationship between the anticoagulant effect of dalteparin and clinical clotting during haemodialysis. We performed an open, prospective study on the effect of decreasing doses of dalteparin in 12 haemodialysis patients during a total of 84 sessions (4-4.5 h). The normally applied dose of dalteparin in each patient was reduced by 25% for each session down to 50% of initial dose if no clotting was observed. Clinical clotting (grade 1-4) was evaluated by visual inspection after blood draining of the air trap every hour and by inspection of the dialyser after each session and compared to corresponding values for anti-FXa activity and dialysis time. Blood flow and ultrafiltration rate were kept within narrow limits throughout the study. No episodes of grade 4 clotting occurred, and no session was interrupted. Eighteen episodes of grade 3 clinical clotting (11%) were observed in patients without warfarin treatment, none with an anti-FXa activity >0.43 IU/ml. Oral warfarin treatment reduced the clinical clotting, and only one grade 3 episode was observed in patients on warfarin therapy. Anti-FXa activity and haemodialysis time were the only factors independently correlated to clotting in a logistic regression model. An anti-FXa activity above 0.4 IU/ml after 4 h of dialysis inhibits significant clotting during haemodialysis. A bolus dose of dalteparin of 70 IU/kg usually seems appropriate, but may be reduced in patients on warfarin treatment. Dialysis time is an independent risk factor for clinical clotting.

Contact between blood and dialysis membranes activates mononuclear cells and the complement system. The extent of activation is dependent on the dialyser material used and is considered an index of biocompatibility. Polyamide dialysers consist of a synthetic membrane that claims high standards of biocompatibility. Haemophan dialysers represent membranes made of modified cellulose that are now broadly used for treatment in Europe and are already considered to be more biocompatible than the cuprophane membranes that were used as reference in most previous studies. In a cross-over treatment study short-term as well as long-term effects of a polyamide dialyser with respect to monokine induction and complement activation were compared to a haemophan dialyser. Neither haemophan nor polyamide dialysers induced relevant changes in plasma monokine levels. However, in vitro challenge of mononuclear cells with lipopolysaccharide (LPS) unmasked a significantly stronger preactivation for the secretion of proinflammatory monokines during haemophan than polyamide dialysis. Unlike other monokines the production of the regulatory monokine IL-10 was mainly influenced by individual factors and correlated with the patient's immune status rather than the dialyser type used. Enhanced preactivation of monocytes in haemophan compared to polyamide dialysis was paralleled by an increased complement activation. Cellular preactivation and formation of terminal complement complex remained constant over the 4-month treatment period. Haemophan and polyamide dialysers do not induce changes in plasma cytokine levels both during short-term and long-term use. However, they significantly differ in complement activation as well as preactivation of monocytes. Preactivated monocytes are prone to secrete high amounts of proinflammatory cytokines when exposed to a second stimulus like endotoxin. Secretion of the regulatory cytokine IL-10 is not influenced by the dialyser type.