Complement (C) activation, neutropenia, and mild pulmonary dysfunction attend hemodialysis (HD) with cellophane [for example, cuprophan (Cu)] membranes. While usually asymptomatic, these phenomena may cause distress in patients with cardiopulmonary disease, and 'start-up' symptoms of HD might be mediated by C-stimulated granulocytes (PMNs). Cellulose acetate (CA) hemodialysis membranes have been devised and claimed more blood compatible than Cu. In a blinded series of HD patients, puritis, fatigue, and sense of well-being were each scored statistically more favorably by the patients during HD with CA than during HD with Cu (P < 0.05). Postulating that less C activation might underlie the benefit, we showed that neutropenia was less severe with CA (nadir 77.6% of initial count, ± 4 SEM) than with Cu (38.3% ± 2.9; P < 0.01). In vitro, incubation of CA membranes with plasma led to less C3 conversion (20% vs. 40%), less PMN aggregating activity (5.9 ZAP units vs. 3.3) and less decrement in CH50 (6.5% vs. 22%) than like incubations of Cu. C activation was also less potent in vivo: During HD plasma C3a rose form a mean 401 ng/ml to a peak, 6,325 in patients on Cu dialyzers, but from 426 to only 3,637 in patients on CA devices (P < 0.05). Time-course studies suggested CA was initially as potent an activator as Cu but rapidly lost ability to activate C, possibly because of saturation of C3b binding sites. As an index of PMN activation, we also assayed plasma lactoferrin and found levels significantly higher during Cu than CA dialysis. We conclude that CA is better tolerated as a HD membrane than is Cu, and suggest improved tolerance results from the lesser ability of CA to activate plasma C and in turn to stimulate PMNs.
Bibliographical noteFunding Information:
This work was supported by National Institutes of Health grants HL-26218, HL-19725, and Al 16984 and a grant from the Riley Memorial Association. Dr. D. E. Hammerschmidt is the recipient of a Young