New molecular aspects of chronic uraemia and dialysis-related immunocompetent cell activation

Our knowledge of the molecular structure and the role of cell receptors and soluble mediators controlling immune responses has increased tremendously over the last 10 years. Likewise the concept of bioincompatibility resulting from the interaction between extracorporeal blood and the dialysis circuit has been extended far beyond its original definition by complement activation and subsequent pulmonary sequestration of neutrophils. The recent report of the consensus conference on biocompatibility of extracorporeal blood treatment (held in March 1993 in Koenigswinter, Germany), published in a supplement of this journal, has already reviewed in depth the current concepts and knowledge of the mechanisms of bioincompatibility pathways. The major highlights of this report are: a revisit of definitions and terminology used for biocompatibility with particular emphasis on clinical practice, meeting the approval of scientists as well as leading manufacturers; a critical evaluation of the scientific basis and the delimitations of biocompatibility assessment, given the extraordinary complexity of the homeostatic system, the existence of multiple feedback control mechanisms and the interaction networks of these pathways; a series of brief and updated reviews of major fields of biocompatibility, e.g. homeostasis and thrombosis, hypersensitivity, complement activation, stimulation of phagocytic cells, basophils and mast cells, and generation of proinflammatory cytokines; and overviews of experimental systems and in vitro assays for assessment of biocompatibility and of the clinical relevance of bioincompatibility by major specialists in the fields. In their concluding remarks Drs H. Klinkmann and A. M. Davison [1] re-emphasized the major consensus of this conference, i.e. 'the issue of biocompatibility can be considered as a puzzle comprising many different pieces which are slowly being put together, but as yet the complete picture has not emerged'. In this paper we have focused on the new molecular