Activation of Complement, Generation of C5a, Leukopenia and Hypoxemia: Interlinked Membrane-Dependent Events during Hemodialysis

Abstract

Differences in biocompatibility of various hemodialysis membranes cause different degrees of complement activation, leukopenia, and hypoxemia during hemodialysis. In order to further clarify the complex sequence of activation of complement, leukopenia and dialysis hypoxemia, we followed leukocyte count and arterial oxygen tension in 23 patients during two successive dialyses using membranes based on regenerated cellulose (RC) and cellulose acetate (CA). In 12 of the patients, signs of complement activation were investigated by following changes in arterial levels of total hemolytic complement, plasma C3d and C5a. Furthermore, C5a was determined in plasma from the dialyzer effluent line. The study demonstrates basic differences in biocompatibility of the two membranes: hemodialysis using RC membranes was associated with more pronounced leukopenia and hypoxemia than dialysis with CA membranes and, during dialysis using RC membranes, generation of C5a in the dialyzer was evident by demonstration of high values of this anaphylatoxin in dialyzer effluent plasma at the beginning of treatment with gradual decline towards detection limit at the end. Plasma C3d in arterial blood rose during dialyses with both RC and CA membranes, but significantly more with RC, suggesting that accumulation of this complement fraction may serve as a sensitive parameter for complement activation during hemodialysis.Our results suggest a pivotal role of C5a for hemodialysis-induced leukopenia and show that activation of complement, leukopenia, and arterial hypoxemia are interlinked membrane-dependent events.