title: Resistance to intercompartmental mass transfer limits beta2-microglobulin removal by post-dilution hemodiafiltration.
abstract: Although clearance of beta(2)-microglobulin is greater with hemodiafiltration than with high-flux hemodialysis, beta(2)-microglobulin concentrations after long-term hemodiafiltration are only slightly less than those obtained with high-flux hemodialysis. Resistance to beta(2)-microglobulin transfer between body compartments could explain this observation. beta(2)-Microglobulin kinetics were determined in patients receiving on-line post-dilution hemodiafiltration for 4 h with 18 l of filtration. Plasma beta(2)-microglobulin concentrations were measured during and for 2 h following hemodiafiltration and immediately before the next treatment. The filter clearance of beta(2)-microglobulin was determined from arterial and venous concentrations. The beta(2)-microglobulin generation rate was calculated from the change in the plasma concentration between treatments. The intercompartmental clearance was obtained by fitting the observed concentrations to a two-compartment, variable volume model. The plasma clearance of beta(2)-microglobulin by the filter was 73 +/- 2 ml/min. Plasma beta(2)-microglobulin concentrations decreased by 68 +/- 2% from pre- to post-treatment (27.1 +/- 2.2-8.5 +/- 0.7 mg/l), but rebounded by 32+/-3% over the next 90 min. The generation rate of beta(2)-microglobulin was 0.136 +/- 0.008 mg/min. The model fit yielded an intercompartmental clearance of 82 +/- 7 ml/min and a volume of distribution of 10.2 +/- 0.6 l, corresponding to 14.3 +/- 0.7% of body weight. Hemodiafiltration provides a beta(2)-microglobulin clearance of similar magnitude to the intercompartmental clearance within the body. As a result, intercompartmental mass transfer limits beta(2)-microglobulin removal by hemodiafiltration. This finding suggests that alternative strategies, such as increased treatment times or frequency of treatment, are needed to further reduce plasma beta(2)-microglobulin concentrations.
authors.affiliation: Department of Medicine, University of Louisville, Kentucky 40202-1718, USA. richard.ward@kdp.louisville.edu
authors.forename: R A
authors.initials: RA
authors.lastname: Ward
authors.forename: T
authors.initials: T
authors.lastname: Greene
authors.forename: B
authors.initials: B
authors.lastname: Hartmann
authors.forename: W
authors.initials: W
authors.lastname: Samtleben
mesh_terms: D000328:Adult; D000368:Aged; D001825:Body Fluid Compartments; D001835:Body Weight; D005260:Female; D017583:Hemodiafiltration; D015312:Hemodialysis Solutions / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D001613:beta 2-Microglobulin / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D015312:Hemodialysis Solutions; D001613:beta 2-Microglobulin