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Background: Increased middle-molecular uremic toxin removal seems to favorably influence survival in dialysis patients. The aim of this study was to verify if, in on-line mixed hemodiafiltration, solute removal by convection may be enhanced by forcing the ultrafiltration rate (QUF) and optimizing the infusion technique in order to achieve the highest possible filtration fraction (FF)., Methods: Removal of beta2-microglobulin (beta2-m), urea, creatinine, and phosphate were compared in 20 patients randomly submitted to one dialysis session (A), one postdilution hemodiafiltration session (B), and three sessions of mixed hemodiafiltration (C, D, and E) at different infusion rates (QS). In mixed hemodiafiltration, a newly developed feedback system automatically maintained the transmembrane pressure (TMP) within its highest range of safety (250 to 300 mm Hg) at constant QUF, while ensuring the maximum FF by splitting infusion between pre- and postdilution., Results: A mean QS of 134 +/- 20 mL/min (mean FF = 0.65) was attained in post-HDF, and up to 307 +/- 41 mL/min (mean FF = 0.69) in mixed hemodiafiltration. The mean dialysate clearances (KDQ) for all tested solutes and urea eKt/V were significantly higher in all hemodiafiltration sessions than in dialysis. Only in the case of urea did the infusion mode have no significant effect. KDQ for beta2-m was maximal in session D and significantly higher than in session B (90.2 +/- 11 mL/min vs. 77.5 +/- 11 mL/min; P = 0.02). KDQ for beta2-m significantly correlated with QS and the plasma water flow rate (QPW). The highest KDQ for beta2-m was found at values of QS approximately QPW. Beyond this value KDQ decreased., Conclusion: The mixed infusion mode in hemodiafiltration, controlled by the TMP-ultrafiltration feedback, seems to improve the efficiency of hemodiafiltration by fully exploiting the convective mechanism of solute removal. The feedback automatically adjusted the infusion rate and site to the maximum FF taking into account flow conditions, internal pressures, and hydraulic permeability of the dialyzer and their complex interactions.

Background: On postdilution hemodiafiltration (post-HDF), convective removal of medium-high molecular weight solutes is, at the highest ultrafiltration rates, limited by high blood viscosity and protein concentration. Prefilter reinfusion (pre-HDF) may overcome this problem, but plasma dilution may affect the overall efficiency of the technique. In this study, an experimental system of online HDF with combined prefilter and postfilter infusion (mixed HDF) was evaluated and compared with the traditional predilution and postdilution modes., Methods: Removal of urea (U), creatinine (Cr), phosphate (Phos), and beta(2)-microglobulin (beta(2)m), ultrafiltration coefficients of the dialyzer (K(UF)), and rheologic conditions of the blood circuit were evaluated during the three infusion modes (a total of 36 runs lasting 180 min), performed with a polysulfone hemofilter 1.8 m(2), blood flow (Q(b)) 400 mL/min, dialysate flow (Q(d)) 700 mL/min, and infusion rate 120 mL/min (pre-HDF and post-HDF), or 60 + 60 mL/min (mixed HDF)., Results: The mean effective U and Cr clearances and urea index of dialysis dose (eKt/V) were significantly higher on post-HDF than on pre-HDF (K(WB) (U) 210 vs. 193 mL/min, K(DQ) (Cr) 152 vs. 142 mL/min, eKt/V 1.41 vs. 1.30), while mixed HDF did not show significant differences versus post-HDF (K(WB) (U) 201 mL/min, K(DQ) (Cr) 149 mL/min). K(DQ) for Phos and beta(2)m were higher on post-HDF in only absolute values. Similar differences were found for instantaneous dialyzer clearances (K(I)) at 60, 120, and 180 minutes of the sessions, with a common trend to decrease with time. K(UF) and the apparent beta(2)m sieving coefficient showed their lowest values toward the end of post-HDF sessions. Increasing filtration fractions (FFs) were associated with increasing transmembrane pressure (TMP) and solute clearances up to FF values of 0.45. These were values achieved in only post-HDF, at which point the curve of the relationship between TMP and FF assumed its steepest exponential trend., Conclusions: Mixed HDF, by better preserving the characteristics of water and solute transport of the membrane, ensured safer operating conditions than post-HDF, while achieving similar removal of small- and large-size solutes. Optimizing the ratio of prefilter/postfilter infusion and the total infusion according to the relationships found in our study between solute clearances, FF, and TMP, convective flux and transport may avoid excessive hemoconcentration and dangerous pressure gradients.