Filtration of native and glycated beta(2)-microglobulin by charged and neutral dialysis membranes

Background. It has been postulated that protein glycation and formation of advanced glycation end products (AGE) are among toxic factors in chronic ur emia, whether the renal disease is of diabetic or nondiabetic origin. In th is setting, AGE-modified beta (2)-microglobulin (beta (2)m) may favor dialy sis beta (2)m-related dialysis amyloidosis. Consequently, efficient removal of modified beta (2)m by highly permeable dialysis membranes is as importa nt as removal of native beta (2)m to postpone the development of dialysis a myloidosis. Methods. To define the role of dialysis membrane surface electronegativity on plasma protein transfer, an in vitro model was used to test the interact ions of native and glycated beta (2)m with various highly permeable dialysi s membranes. An experimental circuit with minidialyzers was used. The neutr al high-flux polysulfone membrane (PS), the electronegative polymethylmetac rylate membrane (PMMA), the electronegative AN69 membrane and a modified AN 69 membrane, the surface of which was neutralized with polyethyleneimine (A N69-PEI), were tested using both native beta (2)m and the more acidic glyca ted beta (2)m. Protein mass transfer and binding to the membrane were measu red. Results. Mass transfer of glycated beta (2)m was significantly decreased th rough all membranes tested when compared with native P-m. This result was d ue to the increased molecular weight of P-m, which became less permeable to porous membranes, whereas adsorption of both native and glycated beta (2)m to membranes, due to ionic interactions, decreased similarly with AN69 and AN69-PEI, but remained unchanged with PS and PMMA. Moreover, surface neutr alization of AN69 membrane did not alter its core binding capacity, since b eta (2)m absorption accounted for 98 and 97% and glycated beta (2)m for 83. 7 and 81.4% of the protein removed with AN69 and AN69-PEI, respectively. Conclusion. Clearance of glycated beta (2)m through highly permeable neutra l and negatively charged membranes was lower than that of native beta (2)m, reflecting a decreased sieving coefficient for the neoformed higher molecu lar weight and conformationally altered molecule. The binding capacity of t he neutral PS was roughly half that of the charged membranes. Neutralizing surface electronegativity of the AN69 membrane with PEI did not alter its b inding capacity. These results suggest that it would be useful for dialysis protocols to include comparative studies of both serum native and modified beta M-2 in order to prevent beta (2)m-amyloidosis.