In the late 1960s, ultrafiltration was first used in clinical settings to increase, by convection, the clearance of toxic solutes in patients undergoing dialysis. Unfortunately, the efficiency of convection-based dialysis treatment, or hemofiltration (HF), was limited by the relatively low ultrafiltration coefficient of the dialyzers available at the time. Thus, the exchanged volume was low, and the corresponding clearance of low-molecular-weight solutes was insufficient with respect to the current target value of Kt/V urea. This was probably the cause of the failed improvement in the clinical and metabolic status of patients compared with standard dialysis treatment. In 1977, favorable results of the combination of diffusion and convection demonstrated the potential advantage of hemodiafiltration (HDF) over HF in terms of dialysis clearance. HDF was in fact the only means to obtain significant clearance of high-molecular-weight solutes while maintaining adequate urea clearance, whereas the increase in mean hematocrit in the erythropoietin era limited the exchanged volume in HF, in spite of the improved water permeability of the dialysis membranes. Mixed diffusive and convective clearance is less than the sum of the two parts because of reciprocal interference. Diffusive clearance mainly depends on the membrane permeability and the solute concentration gradient. New, highly permeable dialysis membranes can reach significant clearance of high-molecular-weight solutes such as Beta2 microglobulin (B2m) simply by diffusion, although in clinical settings there is also considerable “hidden” convection due to backfiltration. However, convection remains the best way to remove high-molecular-weight solutes, also for this kind of membrane. The ultrafiltration rate and the sieving coefficient account for the amount of convective clearance, as described in detail in the text. To define the treatment dose, the equation of Waniewsky allows the theoretical calculation of the urea clearance in HDF, both in postdilution and predilution mode. Unfortunately, no such equation is available for B2m. With a new mathematical model, well fitting with preliminary measured data although not fully validated, we calculated the relationship between urea and B2m clearance in predilution versus postdilution HDF, also considering the impact of variables such as blood and ultrafiltration flow. In particular, the predilution mode may decrease the urea clearance in comparison to hemodialysis with the same membrane and blood flow. This also applies to B2m clearance in predilution vs postdilution HDF, in spite of a marked increase in the ultrafiltration rate, at least in the more common clinical settings. In conclusion, good knowledge of the physics of solute transport is mandatory for appropriate prescription of HDF, in order to maximize both low- and high-molecular-weight solute clearance.
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