Filtration of native and glycated β2-microglobulin by charged and neutral dialysis membranes

Filtration of native and glycated β 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 uremia, whether the renal disease is of diabetic or nondiabetic origin. In this setting, AGE-modified β 2 -microglobulin (β 2 m) may favor dialysis β 2 m-related dialysis amyloidosis. Consequently, efficient removal of modified β 2 m by highly permeable dialysis membranes is as important as removal of native β 2 m to postpone the development of dialysis amyloidosis. Methods To define the role of dialysis membrane surface electronegativity on plasma protein transfer, an in vitro model was used to test the interactions of native and glycated β 2 m with various highly permeable dialysis membranes. An experimental circuit with minidialyzers was used. The neutral high-flux polysulfone membrane (PS), the electronegative polymethylmetacrylate membrane (PMMA), the electronegative AN69 membrane and a modified AN69 membrane, the surface of which was neutralized with polyethyleneimine (AN69-PEI), were tested using both native β 2 m and the more acidic glycated β 2 m. Protein mass transfer and binding to the membrane were measured. Results Mass transfer of glycated β 2 m was significantly decreased through all membranes tested when compared with native β 2 m. This result was due to the increased molecular weight of β 2 m, which became less permeable to porous membranes, whereas adsorption of both native and glycated β 2 m to membranes, due to ionic interactions, decreased similarly with AN69 and AN69-PEI, but remained unchanged with PS and PMMA. Moreover, surface neutralization of AN69 membrane did not alter its core binding capacity, since β 2 m absorption accounted for 98 and 97% and glycated β 2 m for 83.7 and 81.4% of the protein removed with AN69 and AN69-PEI, respectively. Conclusion Clearance of glycated β 2 m through highly permeable neutral and negatively charged membranes was lower than that of native β 2 m, reflecting a decreased sieving coefficient for the neoformed higher molecular weight and conformationally altered molecule. The binding capacity of the neutral PS was roughly half that of the charged membranes. Neutralizing surface electronegativity of the AN69 membrane with PEI did not alter its binding capacity. These results suggest that it would be useful for dialysis protocols to include comparative studies of both serum native and modified β 2 m in order to prevent β 2 m-amyloidosis.