title: Filtration of native and glycated beta2-microglobulin by charged and neutral dialysis membranes.
abstract: 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 beta2-microglobulin (beta2m) may favor dialysis beta2m-related dialysis amyloidosis. Consequently, efficient removal of modified beta2m by highly permeable dialysis membranes is as important as removal of native beta2m 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 beta2m 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 beta2m and the more acidic glycated beta2m. Protein mass transfer and binding to the membrane were measured.
  
  
  RESULTS
  Mass transfer of glycated beta2m was significantly decreased through all membranes tested when compared with native beta2m. This result was due to the increased molecular weight of beta2m, which became less permeable to porous membranes, whereas adsorption of both native and glycated beta2m 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 beta2m absorption accounted for 98 and 97% and glycated beta2m for 83.7 and 81.4% of the protein removed with AN69 and AN69-PEI, respectively.
  
  
  CONCLUSIONS
  Clearance of glycated beta2m through highly permeable neutral and negatively charged membranes was lower than that of native beta2m, 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 beta2m in order to prevent beta2m-amyloidosis.
authors.affiliation: Service de Néphrologie and Laboratoire de Biochimie, Centre Hospitalier et Universitaire, Reims, France.
authors.forename: C
authors.initials: C
authors.lastname: Randoux
authors.forename: P
authors.initials: P
authors.lastname: Gillery
authors.forename: N
authors.initials: N
authors.lastname: Georges
authors.forename: S
authors.initials: S
authors.lastname: Lavaud
authors.forename: J
authors.initials: J
authors.lastname: Chanard
mesh_terms: D000180:Acrylic Resins; D000181:Acrylonitrile / Q000031:analogs & derivatives*; D000686:Amyloidosis / Q000517:prevention & control; D001672:Biocompatible Materials; D001781:Blood Component Removal / Q000295:instrumentation* / Q000379:methods*; D004560:Electricity; D006031:Glycosylation; D006440:Hemofiltration / Q000295:instrumentation* / Q000379:methods*; D006801:Humans; D007700:Kinetics; D008567:Membranes, Artificial; D011108:Polymers; D019904:Polymethyl Methacrylate; D017582:Renal Replacement Therapy / Q000295:instrumentation*; D013450:Sulfones; D001613:beta 2-Microglobulin / Q000302:isolation & purification* / Q000378:metabolism
chemical_list: D000180:Acrylic Resins; D001672:Biocompatible Materials; D008567:Membranes, Artificial; D011108:Polymers; D013450:Sulfones; D001613:beta 2-Microglobulin; C017662:polysulfone P 1700; C016892:AN-69; D019904:Polymethyl Methacrylate; D000181:Acrylonitrile