Kinetics of β -2-Microglobulin with Hemodiafiltration and High-Flux Hemodialysis.

Key Points: Addition of hemodiafiltration has a relatively small impact on reducing either predialysis or time-averaged serum -2-microglobulin levels. Residual kidney function has a major impact on the predialysis and time-averaged serum -2-microglobulin levels.

Background: A kinetic model for -2-microglobulin removal and generation was used to explore the impact of adding hemodiafiltration on predialysis and time-averaged serum values.

Methods: The model was tested on data from the HEMO study and on a sample of patients undergoing high-flux hemodialysis. The impact of hemodiafiltration on -2-microglobulin levels was evaluated by modeling four randomized studies of hemodiafiltration versus hemodialysis. The impact of residual kidney function on -2-microglobulin was tested by comparing results of previously reported measured data with model predictions.

Results: In the low-flux and high-flux arms of the HEMO study, measured median -2-microglobulin reduction ratios could be matched by dialyzer clearances of 5.9 and 29 ml/min, respectively. Median predialysis serum -2-microglobulin levels were matched if generation rates of -2-microglobulin were set to approximately 235 mg/d. In another group of patients treated with dialyzers with increased -2-microglobulin clearances, measured cross-dialyzer clearances (57±28 ml/min) were used as inputs. In these studies, the kinetic model estimates of intradialysis and early postdialysis serum -2-microglobulin levels were similar to median measured values. The model was able to estimate the changes in predialysis serum -2-microglobulin in each of four published randomized comparisons of hemodiafiltration with hemodialysis, although the model predicted a greater decrease in predialysis serum -2-microglobulin with hemodiafiltration than was reported in two of the studies. The predicted impact of residual kidney clearance on predialysis serum -2-microglobulin concentrations was similar to that reported in one published observational study. Modeling predicted that postdilution hemodiafiltration using 25 L/4 hours replacement fluid would lower serum time-averaged concentration of -2-microglobulin by about 18.2%, similar to the effect of 1.50 ml/min residual kidney GFR.

Conclusions: A two-pool kinetic model of -2-microglobulin yielded values of reduction ratio and predialysis serum concentration that were consistent with measured values with various hemodiafiltration and hemodialysis treatment regimens.