Measurable complement activation resulting in the formation of both C3a and C5a anaphylatoxins was observed in 12 patients undergoing maintenance dialysis treatment with cuprophan hollow fiber dialyzers. Specific radioimmunoassay measurements demonstrated that these patients displayed significantly elevated levels of C3a antigen in the venous (outflow) line of the dialyzer after only 2 min of dialysis. During hemodialysis, venous plasma C3a levels continued to increase and became maximally elevated after 15 min. Thereafter, C3a concentrations gradually declined, suggesting that the rate of complement activation abates with continued cuprophan hemodialysis. Complement activation, as judged by venous plasma C3a levels, was also temporally correlated with hemodialysis leukopenia. The factor believed to be responsible for pulmonary vascular leukosequestration, C5a, could also be detected in venous plasma, but levels of this antigen were not strikingly elevated until the later stages of dialysis. By contrast, six patients dialyzed with polyacrylonitrile dialyzers failed to exhibit hemodialysis leukopenia and displayed only very modest increases in their plasma C3a levels during the initial phases of hemodialysis. These observations provide direct evidence that anaphylatoxin formation during hemodialysis is a transient phenomenon and indicate that the biocompatibility of dialysis membranes, as reflected by their complement activating potential, may be significantly different.

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Hemodialysis of 11 endstage renal failure patients with new cuprophan hollow fiber dialyzers produced significant leukopenia as well as increased plasma levels of both C3a and C5a antigens during the initial phases of the procedure. Formalin-fixed new dialyzers produced quantitatively similar phenomena in eight of these same patients. By contrast, hemodialysis with re-used dialyzers, that is dialyzers exposed to blood prior to formalin sterilization, produced only a 20 to 30% decline in peripheral blood leukocyte counts. Correspondingly, C3a antigen formation within re-used dialyzers was only 20% of that observed in new dialyzers. Re-used dialyzers also differed significantly from either new or formalin-fixed new dialyzers in that C3b antigen could be readily detected within them even after extensive washing. These observations suggest that C3b deposition on the cellulosic membrane surface during first use markedly diminishes the complement activating potential of cuprophan dialyzers when they are subsequently re-used.

A B S T R A C T Previous work has shown that use of hypertonic peritoneal dialysis fluid (7% glucose) results in ultrafiltration and enhanced urea transfer across the peritoneal membrane. Simultaneous creatinine studies showed a similar enhancement with hypertonic fluid which persisted in lesser degree during subsequent isotonic exchanges. The mechanism of solvent drag has been shown to contribute significantly to the increased urea removal with ultrafiltration. In the present study, the role of altered diffusive permeability of the peritoneal membrane as suggested by the creatinine data was evaluated as a possible additional mechanism. Hypertonic exchanges were bracketed by isotonic (1.5% glucose) exchanges during 11 studies in four patients.During six other studies in four patients, isotonic exchanges only were performed. A mathematical model for peritoneal solute transport by diffusion was developed and a method to distinguish alterations in peritoneal membrane permeability from changes in membrane area proposed. The method incorporates the determination and comparison of transport characteristics for two test solutes of widely different molecular weights. Alterations in inulin and urea transperitoneal transport characteristics in the above studies indicate a significant increase in membrane permeability after exposure to hypertonic solutions that persists during subsequent isotonic exchanges. Varying patterns of membrane area and permeability changes occurred during repeated exposure to only isotonic exchanges. The