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.

On the Mechanisms of Haemodialysis-induced Neutropenia: A Study with Five New and Re-used Membranes

“…In addition, the positive correlation observed between C 3 d accumulation and C 5 a desarg suggests that these two indicators of complement activation follow the same 781 kinetics, as also demonstrated by others [36,37], thus reflecting the same in vivo phenomenon. Our results show that complement was related to the neutropenia, but that it participated in a quantitatively different way with each membrane.…”

Complement Activation in Plasma Exchange by Single Filtration and Centrifugation and in Cascade Filtration

“…It is rela tively stable and therefore suitable as a marker in clinical studies of complement ac tivation. C3d has been assayed in studies of inflammatory diseases such as systemic lu pus erythematosus [14] and also in evalua tion of the biocompatibility of various de vices used in hemodialysis [6][7][8]. The present results show that estimation of C3d may be a valuable tool also when comparing various procedures of plasma exchange.…”

“…In the present study, we measured complement activation in plasma exchange by single filtration and cen trifugation of blood and in cascade filtration. As a parameter, we used C3d formation, which has previously been found to be a use ful marker of complement activation during hemodialysis [6][7][8].…”

Cellular Hypoxia during Hemodialysis

“…Transitory profound leukopenia attends hemodialysis using cellulosic membranes [14], and has been linked to activation of complement and formation of leukocyte aggregatory activity [15], We have previously reported that activation of complement with generation of anaphylatoxin C5a within the dialyzer and dialysis leukopenia are inter linked events, that depend on the type of dia lyzer membrane used [2], The leukopenia is due to a transitory sequestration/embolization of neutrophiles in the pulmonary' vessels as demonstrated both in animals [15] and man [16].…”

“…The pathophysiology of this arterial hypoxemia has not been elucidated in all details, but the composition of the dialysate [1] and the na ture af the dialyzer membrane [2] seem to contribute.…”