Regenerated cellulosic membranes are held as bioincompatible due to their high
complement - and
leukopenia - inducing properties. Adherence of polymorphonuclear neutrophils and monocyte purified from normal human blood to the three membranes were evaluated in an in vitro recirculation circuit in the presence or absence of fresh, autologous plasma after recirculation in an in vitro circuit using minimodules with each of the three membranes. In in vivo studies, 9 patients were treated with conventional haemodialysis for 2 weeks with each membrane and 1 week for wash-out using haemodialysers with the following surface: 1.95 m2 for benzyl-
cellulose, 1.8 m2 for
acetate-
cellulose and low-flux
polysulfone. Measurement of
leukopenia, plasma
C3a des Arg and elastase-alpha1
proteinase inhibitor complex levels as well as
urea,
creatinine,
phosphate and
uric acid clearances was performed. Plasma-free neutrophils adhered maximally to
acetate-
cellulose (65% remaining in the circulation), while there was no significant difference between low-flux
polysulfone and benzyl-
cellulose (80% circulating neutrophils, at 15 min, p<0.001 vs
acetate cellulose). In the presence of fresh plasma, as source of
complement, the differences between
acetate cellulose vs
polysulfone and benzyl-
cellulose were even more evident, suggesting the role of
complement-activated products in neutrophil adherence. A similar trend was observed for monocyte adherence with the three membranes in the absence or presence of plasma. In vivo studies showed that the nadir of
leukopenia was at 15 and 30 min with
acetate-
cellulose (79%) and benzyl-
cellulose (50%) (p<0.05
acetate- vs benzyl-
cellulose) and at 15 min with
polysulfone (24%) (p<0.01 vs
acetate- and benzyl-
cellulose). Plasma
C3a des Arg levels arose to 2037 +/- 120 ng/ml, 1216 + 434 ng/ml and 46 +/- 55 ng/ml with
acetate-, benzyl-
cellulose and
polysulfone, respectively. No pre- vs post-dialysis increase in the intracellular content of
TNF-alpha was detected with any of three membranes. Clearance values of
urea,
creatinine and
uric acid were superimposable for all the three membranes. However, benzyl
cellulose had a significantly higher clearance for
phosphorus (normalized for surface area) (p<0.01 vs
acetate-
cellulose, 0.001 vs
polysulfone). These results implicate that synthetic modification of the
cellulose polymer as for the benzyl-
cellulose significantly reduces the in vitro adherence, delays the in vivo activation of "classic" biocompatibility parameters and notably improves the removal of inorganic
phosphorus.