Beta-2-microglobulin handling in dialysis.
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Biomedical subjects
Publications and source records attributed to B Klinke.
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One hundred and six unselected patients were screened for allergic symptoms, specific IgE against ethylene oxide (ETO), isocyanates (ISO), formaldehyde (FA), phthalates (PHT), total IgE and eosinophil count. Complement activation was measured during cellulosic dialysis in atopic patients and in a control group. Sixteen patients demonstrated mild allergic symptoms during dialysis treatment. Ten of them had IgE elevation and eosinophilia. Eight of these patients had positive RASTs (ETO: n = 5, ETO-ISO(?)-FA: n = 2, ISO-PHT: n = 1) against dialysis material. All eight had an eosinophilia and seven showed an IgE elevation. An amelioration of symptoms could be obtained in three patients with elevated (greater than 15%) ETO-binding values after switching to ETO-free dialysers; avoiding PHT- and ISO-containing dialysis materials allergic symptoms remained constant. Cuprammonium rayon-induced complement activation had a more rapid onset and was more pronounced in atopic patients. The study confirms the role of ETO, but not of the other dialysis materials in the allergic sensitisation of haemodialysis patients.
Beta-2-microglobulin (b2M) was identified as a causative agent of amyloidosis associated with long-term hemodialysis (HD). Therefore, we examined handling of b2M during a 4-hour hemodialysis session. We compared b2M adsoprtion and diffusive/convective elimination between high-flux membranes such as polysulfone (PS; F 60, Fresenius), polyacrylonitrile (AN 69; Filtral, Hospal) and polyacrylonitrile (PAN, PAN 12CX2, Asahi) and less permeable membranes such as cuprammonium rayon (CR; AM 160 H, Asahi) and polymethylmethacrylate (PMMA; BK-1.6 U, Toray). To calculate total elimination, arterio-venous differences of b2M were measured at 0, 5, 20, 60 and 240 minutes; dialysate concentration was analyzed to evaluate diffusive/convective transport. Differences between recovery in dialysate and total removal were regarded as amount removed by adsorption. Total elimination per 4-hour hemodialysis session and per m2 membrane surface was 154.7 +/- 12.3 mg for the PS, 137.8 +/- 28.4 mg for the AN 69, 179.8 +/- 47.5 mg for the PAN, 130.8 +/- 11.8 mg for the PMMA and 14.4 +/- 16.0 mg for the CR membrane. Diffusive/convective transport was 128.0 +/- 18.1 mg for PS, 54.7 +/- 8.1 mg for AN 69 and 106.5 +/- 20.8 mg for PAN and insignificant for PMMA and CR. Adsorption was 26.7 +/- 4.3 mg for PS, 83.1 +/- 29.0 mg for AN 69 and 59.8 +/- 17.2 mg for PAN. Besides transmembranous transport sorption is an important mode of elimination. Weekly endogenous generation rate is about twice as high as b2M elimination.
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We studied the effects of cuprammonium rayon (CR), polyacrylonitrile (PAN), polysulfone (PS), changes in osmolality, and heparin dosage on beta-2-microglobulin (b2M) handling in an in-vitro model that excluded convective transport and minimized diffusive transport. Both PAN and PS exhibited high adsorption capacity for b2M. Osmolality changes had no effect on b2M adsorption or release. CR membrane adsorption was minimal but increased slightly when higher heparin doses were used. In experiments with CR and high heparin doses (4 U/ml) b2M release occurred during the first 15 minutes of in-vitro dialysis, but this increase was inhibited by removing the leukocytes from the blood, indicating that b2M is released from leukocytes.