Expression of beta(2)-microglobulin and c-fos mRNA: Is there an influence of high- or low-flux dialyzer membranes?

Background. Dialysis-related amyloidosis is an important complication of lo ng-term hemodialysis (I-ID) therapy with several pathogenetic factors. One of them is the influence of the dialyzer membrane type on the synthesis of beta (2)-microglobulin (beta (2)m) In vitro results are controversial. Thus , the hypothesis of whether in vivo beta (2)m generation is induced by the HD procedure and whether this induction depends on the type of the used dia lyzer membrane should he tested. The aim of the present study was to invest igate the influence of "biocompatible" high-flux versus "bioincompatible" l ow-flux I-ID on in vivo Pm generation as well as the induction of the early activation gene c-fos in peripheral blood cells. Methods. Six nondiabetic HD patients [mean age 46 (21 to 69) years; Kt/V > 1.2] were included in a randomized crossover study using either a low-flux (cellulosic/euprophan) or a high-flux (polyamide) dialyzer membrane. At the end of a four-week run-in period fur each membrane, whole blood samples we re taken before, immediately at, and four hours after the end of the dialys is session. MRNA was extracted, and after transcription to cDNA, quantitati ve polymerase chain reaction was performed fur the beta (2)m gene, the earl y response gene c-fos, and the GAP-DH housekeeping gene. Results. Based on the applied method for detection of specific mRNA, the re sults were given as ratio of beta (2)m or c-fos cDNA per GAP-DH cDNA. Gener al cell activation during HD was indicated by increasing mRNA expression of c-fos related to the time course of the dialysis session, whereas beta (2) m did not change significantly. However, no difference was found when compa ring the low-flux and the high-nux dialyzer membranes. Despite the evidence for activation of peripheral blood cells, as indicated by increasing c-fos message, no sign of beta (2)m mRNA induction during I-ID procedure with di fferent dialyzer membranes was seen. Conclusions. Our results suggest that there is post-transcriptional regulat ion of beta (2)m generation and/or release as well as the influence of the dialyzer membrane type on post-translational processes, that is, advance gl ycation end products (AGE) or conformational modification of the beta (2)m protein. Furthermore, our data demonstrate that gene expression patterns du ring dialysis and/or uremia are not homogenous and need to be investigated further, especially with respect to the proinflammatory role of early leuko cyte activation signals.