Evaluation of haemodialysis membrane biocompatibility by parallel assessment in an ex vivo model in health y volunteers

Background. Precise evaluation of thehaemocompatibility of prototype membranes, flow configurations andanticoagulant regimens is an essential step in the development of dialysissystems minimizing blood activation. An ex vivo modelin humans currently employed in our laboratory has recently been adapted toallow the parallel evaluation of two minimodule dialysers with blood from asingle donor, thus eliminating differences due to donor variability in thecomparison of test and control dialysis modules.Methods. The ex vivo flow systemis designed to reproduce the haemodynamic conditions of clinical dialysison a 1/50 scale. A blood line from the forearm vein of the volunteer donoris divided at a Y-shaped junction, two roller pumps assure equivalent bloodflow (5 ml/min) in the branches leading to two minimodule dialysers andheparin (0.1 IU/ml final concentration) is injected into each branchimmediately after the Y junction. Samples for analysis of blood activationmarkers are collected at the exits of the two minimodules over a testperiod of 27 min In the present series of tests, a new polyacrylonitirilemembrane (PAN) was evaluated relative to standard commercial polysulphone(PS), acrylonitrile copolymer (AN 69) and cuprophan (CUP) membranes.Results. A steady minimal level of anticoagulationcorresponding to a slightly less than two-fold prolongation of APTT(activated partial thromboplastin time) was maintained throughout testingin both branches of the ex vivo flow system. Timecurves for the accumulation of activation markers (thrombin-antithrombin IIcomplexes, prothrombin fragment 1+2, platelet {beta}-thromboglobulin,and complement fragment C3a) showed all four types of minimodule dialyserto induce comparable low levels of activation of coagulation parameters andplatelets, together with similar mild activation of complement for AN 69,PAN, and PS dialysers as compared to stronger activation for CUP modules.Overall results thus confirmed the acceptable haemocompatibility of theprototype polyacrylonitrile (PAN) membrane.Conclusions. Among current methods for evaluation ofthe biocompatibility of haemodialysis systems, ex vivoflow models in humans avoid problems arising from species differences andmay be designed to closely reproduce the conditions of clinical dialysis. Aparallel configuration eliminates artefacts due to individual variations indonor response. This not only facilitates the direct comparison of test andcontrol membranes under close to identical experimental conditions, butalso provides a model particularly well adapted to studies of the effectsof different anticoagulation regimens, flow configurations and dialysates,or alternative methods of sterilization, rinsing and priming of thedialysers.