Establishing the Relationship between Complement Activation and Stimulation of Phagocyte Oxidative Metabolism in Hemodialyzed Patients: A Randomized Prospective Study

Abstract

The present prospective study was conducted in order to establish the relationship between complement activation and stimulation of phagocyte oxidative metabolism observed in long-term hemodialysis (HD) patients during the early phase of dialysis with cellulosic membranes. Two groups of 10 randomized (HD) patients treated with cellulosic (Cuprophan, CUP) or synthetic polyacrilonitrile (PAN AN-69®) membranes were studied. Leukocyte counts, C3a antigen plasma concentration and whole blood basal and stimulated chemiluminescence (CL) production were determined in blood samples drawn from the fistula before dialysis (T₀) and from both the afferent and efferent lines of the dialyser at 15 min (T₁₅) and at the end (T_end) of the dialysis session. This study confirms that, coincident with the nadir of leukopenia observed at T₁₅, dialysis with CUP but not PAN membranes induces a marked rise in C3a antigen levels and profound alterations in whole blood CL production consisting of a dramatic increase in basal CL and a significant loss in CL response capacity to stimulating agents. It further demonstrates that a direct relationship exists between the variations in C3a antigen plasma levels and whole blood CL production observed in the CUP group of patients from T₀ to T₁₅ (Δ15) of dialysis. This relationship is characterized by a positive correlation between Δ15 C3a and Δ15 basal CL levels in afferent and efferent lines, and a negative correlation between Δ15 C3a and Δ15 CL response capacity values in the efferent but not afferent line. In contrast, no significant correlation with the type of dialysis membrane could be demonstrated between the variations in polymorphonuclear neutrophil counts and C3a antigen levels. Altogether our results establish the relevance of C3a antigen and reactive oxygen intermediates as in vivo optimal biological parameters of dialysis membrane bioincompatibility and further document the possible role of reactive oxygen intermediates in HD-associated pathology.