Biocompatibility of Haemodialysis Membranes: Haemodialysis-Related Leukotriene B₄ and C₄ Generation

Abstract

The aim of our study was (1) to verify whether haemodialysis (HD) with cuprophane (CUP) and polyacrylonitrile (PAN) membranes is associated with the release of vasoactive leukotriene (LT) C₄ and chemotactic LTB₄ and (2) to analyse the respective roles of lipoxygenase and cyclo-oxygenase metabolites of arachidonic acid in membrane bio-incompatibility. The investigation was performed in 10 uremic patients using hollow-fibre dialysers and dialysed successively, in random order, with CUP and PAN membranes. The arterial and venous (from dialyser) blood was sampled for the measurement of biochemical parameters, plasma LTC₄, LTB₄ and prostaglandins (PG) 6-keto-F1_α, E₂, F_2α and thromboxane B₂ before and after 15, 30 and 240 min of HD. Eicosa-noids were measured by RIA after prior extraction and HPLC separation. Results: CUP HD was associated with a marked early leukopenia and a delayed decrease in blood pO₂. Simultaneously, plasma LTB₄ and LTC₄ increased significantly in arterial blood after 30 min of HD and in venous blood at the end of session of 240 min. Cyclo-oxygenase metabolites increased as well, but nonsignificantly, with a maximum at the end of HD. PAN HD did not significantly change white blood cell count, pO₂ or plasma eicosanoid levels. Conclusion: CUP membranes stimulate the release of proinflammatory and vasoactive LTB₄ and LTC₄. PAN membrane haemodialysis is without such side effects. The release of LTs may be an additional valuable marker of membrane bioincompatibility.

Hemodialysis-lnduced Upregulation of Granulocyte Adhesion Molecules CD 11b/CD18 Is Independent from 5-Lipoxygenase Activity

“…This is further supported by the marginal changes in LTB4 plas ma levels during ex vivo dialysis with cuprophane mem branes. In contrast, plasma levels of LTB4 have been found to markedly increase in the first minutes of dialysis with cuprophane membranes in uremic patients main tained on hemodialysis with cuprophane membranes [6,7], Our data indicate that activation of 5-lipoxygenase during in vivo dialysis with cuprophane membranes par allels but does not underly upregulation of CD1 lb/CD18 expression.…”

“…C3a des Argand C5a des Arg, increases shortly after onset of dialysis with new cupro phane membranes [1]. However, stimulation of thecom-plement system may only be intermediate to CD1 lb and CD18 expression: (i) complement fragments stimulate granulocyte leukotriene B4(LTB4) formation [4], and (ii) LTB4 upregulated expression of CDllb and CD 18 on PMNLs [5], Furthermore, LTB4 plasma levels increase during the first minutes of in vivo dialysis with cupro phane membranes [6,7], suggesting that activation of 5-lipoxygenase may be involved in dialysis-induced upregu lation of CD1 lb and CD18. Using the specific 5-lipoxy genase inhibitor BAY X1005 which inhibits activation of 5-lipoxygenase by binding to the 5-lipoxygenase activat ing protein [8], we assessed the role of 5-lipoxygenase in the upregulation of CDllb and CD 18 expression on PMNL during ex vivo dialysis with new cuprophane or new acrylonitrile membranes.…”

Increased whole blood chemiluminescence in patients with chronic renal failure independent of hemodialysis treatment

“…This suggests that some agents (e.g. TNF-α, LTB 4 ), released in consequence of blood contact with the dialyzer cuprophane membrane [18,19], are not the main factors responsible for increased pre-HD LBCL. In addition, their catabolism in plasma and diffusion through the dialyzer membrane into the dialyzing fluid [29,41] can strongly limit the duration of the stimulatory effect on blood phagocytes.…”

Continuous interleukin‐6 application in vivo via macroencapsulation of interleukin‐6–expressing COS‐7 cells induces massive gliosis

“…As well as using thin cannulas and polymer membranes, the material of the membrane is very important for the cause of the host reaction. We used a membrane that is also used in dialysis therapy of patients with renal failure and was developed for a high biocompatibility (Hornych et al, 1996). Because of new, upcoming therapeutic strategies within the CNS, we think it is very important to elucidate the implantation of new materials into the CNS, because major side effects of these materials might be due to the activation of glial cells (Fisher, 1995).…”