Beta 2-microglobulin Removal by Synthetic Dialysis Membranes. Mechanisms and Kinetics of the Molecule

1997 ◽  
Vol 20 (3) ◽  
pp. 136-143 ◽  
Author(s):  
C. Ronco ◽  
A. Heifetz ◽  
K. Fox ◽  
C. Curtin ◽  
A. Brendolan ◽  
...  

Beta 2-microglobulin (ß2-m) accumulation represents a possible complication of long term dialysis. It is therefore important to evaluate the capacity of removal of this molecule from the patient by different dialysis membranes. The present study is aimed at evaluating the mechanisms involved in ß2-m removal by three different synthetic membranes: a) highly asymmetric hydrophobic polysulfone (Biosulfane, NMC), b) moderately asymmetric and hydrophobic polysulfone (PS600, Fresenius), c) Polyacylonitrile (AN69HF, Hospal). The adsorption capacity and sieving coefficients of the three membranes for native and labeled ß2-m were studied in vitro utilizing human blood. The amount adsorbed by the membrane was measured by the elution of the molecule obtained with a detergent solution. Clearances, total removal and membrane adsorption were studied in six patients treated in a randomized sequence with the three membranes. For this purpose, plasma and dialysate measurements as well as total collection of spent dialysate and ß2-m elution from the used dialyzers were carried out. Ex novo generation of ß2-m did not take place during in vitro circulation. The molecule was removed by the studied membranes both by filtration and adsorption. The Biosulfane membrane removed ß2-m mostly by adsorption while the PS600 membrane removed ß2-m almost entirely by filtration. Intermediate behaviour was shown by AN69 membrane. Similar quantities of ß2-m were removed from the patients with the three membranes. Total removal could only be precisely measured by adding the quantity of ß2-m eluted from the membrane to the amount recovered in the spent dialysate. Out of total removal, adsorption was more than 90% with Biosulfane, while only 5% with the PS600. These findings contribute to the understanding of the discrepancy found between the clearance measured from the plasma side and that measured from the dialysate side. In conclusion, clearance and sieving measurements for ß2-m cannot be correctly performed unless the capacity of adsorption of the membrane is taken into account.

1989 ◽  
Vol 12 (11) ◽  
pp. 697-702 ◽  
Author(s):  
B. Klinke ◽  
A. Röckel ◽  
S. Abdelhamid ◽  
P. Fiegel ◽  
D. Walb

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; FiltralR, Hospal) and polyacrylonitrile (PAN, PAN 12CX2R, Asahi) and less permeable membranes such as cuprammonium rayon (CR; AM 160 HR, Asahi) and polymethylmethacrylate (PMMA; BK-1.6 UR, 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


Nephron ◽  
1990 ◽  
Vol 56 (3) ◽  
pp. 267-270 ◽  
Author(s):  
Leszek Paczek ◽  
Roland M. Schaefer ◽  
August Heidland

Author(s):  
Michael L. Branham ◽  
T. Govender ◽  
Edward A. Ross

The objectives in this study were to compare the removal of 2-M via different dialyzers (high- and low flux) under equilibrium or sink conditions, wherein there was highly selective antibody-based facilitated transport into a small volume dialysate reservoir. Using an in vitro haemodialysis model we perfused high-flux polymethylmethacrylate (PMMA), high-flux cellulose diacetate (CDA), and a low-flux polysulfone (PSF) membranes with known amounts of 2-M through the intracapillary space. Anti-2-M antibodies added to the extracapillary space were shown to create sink conditions across the membrane when its pore size is sufficiently large for diffusion and if 2-M is not strongly adsorbed to the membrane surface. Our results indicate that 2-M (~12kDa) does not penetrate low-flux dialyzers and that its adsorption to intracapillary PSF surfaces does not substantially affect clearance. 2-M strongly adsorbed to high-flux PMMA dialyzers (ko = 0.0271+0.002 min-1), but without significant clearance enhancement due to circulating antibodies. A significant clearance enhancement (101.2%+24.89) for 2-M due to immunoextraction was observed in the high-flux cellulose acetate dialyzers, but without passive adsorption to the surface. These studies demonstrate the utility of in vitro haemodialysis experiments to elucidate midsize molecule clearance in dialysis membranes under controlled conditions. The use of anti-2-M antibodies as dialysate additives might be feasible in the removal of 2-M from whole blood, highlighting the advantages of selective antibody-based extraction of disease-causing toxins into potentially simple extracorporeal devices with small volume receiver compartments.


1989 ◽  
pp. 251-253
Author(s):  
D. Bonucchi ◽  
L. Lucchi ◽  
G. Cappelli ◽  
A. Stefani ◽  
A. Baraldi ◽  
...  

Immunobiology ◽  
1988 ◽  
Vol 177 (1) ◽  
pp. 55-65 ◽  
Author(s):  
K. Nachbaur ◽  
J. Troppmair ◽  
P. Bieling ◽  
B. Kotlan ◽  
P. König ◽  
...  

1989 ◽  
Vol 9 (3) ◽  
pp. 177-183 ◽  
Author(s):  
William J. Stone ◽  
Raymond M. Hakim

1987 ◽  
Vol 40 (10) ◽  
pp. 1247-1251 ◽  
Author(s):  
J M Theaker ◽  
A E Raine ◽  
A J Rainey ◽  
A Heryet ◽  
A Clark ◽  
...  

1992 ◽  
Vol 15 (7) ◽  
pp. 401-407 ◽  
Author(s):  
K. Kumano ◽  
M. Nanbu ◽  
S. Kusakari ◽  
T. Sakai

Beta 2 microglobulin (B2M) has been identified as a major component of amyloid deposits. This study was designed to determine whether changes occur in the synthesis of B2M in dialysis patients. Mononuclear cells (MNC) were isolated in peripheral blood from healthy volunteers, patients on hemodialysis (HD) and on continuous ambulatory peritoneal dialysis (CAPD). MNC were cultured in a medium of RPMI 1640 with or without interleukins IL-1, IL-2 or interferon INF-r. B2M in the cultured cells and supernatant was measured by enzyme immunoassay. IL-2 or INF-r stimulated B2M synthesis 'was significantly lower (25%) in patients on HD than in normal controls regardless of the type of dialysis membranes used, with no change in basal B2M synthesis. No differences were detected between healthy volunteers and CAPD patients. Preincubation of MNC with complement - activating or non-complement - activating membrane had no influence on B2M synthesis. The basal B2M synthesis of MNC significantly increased after a 4-hour HD regardless of the membranes used, and IL-2 and IFN-r stimulated synthesis were both essentially the same before and after HD. It was thus concluded that maximum capacity for B2M synthesis of MNC decreases in hemodialysis patients. This low responsiveness of MNC may be partially the cause for the reduction in cell-mediated immune response in HD patients.


2001 ◽  
Vol 19 (3) ◽  
pp. 301-307 ◽  
Author(s):  
Chun-Liang Lin ◽  
Chih-Wei Yang ◽  
Chin-Chen Chiang ◽  
Ching-Tung Chang ◽  
Chiu-Ching Huang

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