Resistance to intercompartmental mass transfer limits β2-microglobulin removal by post-dilution hemodiafiltration

Although clearance of β2-microglobulin is greater with hemodiafiltration than with high-flux hemodialysis, β2-microglobulin concentrations after long-term hemodiafiltration are only slightly less than those obtained with high-flux hemodialysis. Resistance to β2-microglobulin transfer between body compartments could explain this observation. β2-Microglobulin kinetics were determined in patients receiving on-line post-dilution hemodiafiltration for 4 h with 18 l of filtration. Plasma β2-microglobulin concentrations were measured during and for 2 h following hemodiafiltration and immediately before the next treatment. The filter clearance of β2-microglobulin was determined from arterial and venous concentrations. The β2-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 β2-microglobulin by the filter was 73±2 ml/min. Plasma β2-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 β2-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 β2-microglobulin clearance of similar magnitude to the intercompartmental clearance within the body. As a result, intercompartmental mass transfer limits β2-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 β2-microglobulin concentrations