Effect of increasing dialyzer mass transfer area coefficient and dialysate flow on clearance of protein-bound solutes: a pilot crossover trial.

BACKGROUND: Protein-bound solutes are poorly cleared by means of conventional hemodialysis because protein binding limits the "free" solute concentration driving diffusion. This study tested the modeled prediction that clearances of bound solutes could be increased by increasing the dialyzer mass transfer area coefficient (K(o)A) and dialysate flow (Q(d)) to greater than the levels used in conventional practice. STUDY DESIGN: Pilot crossover trial. SETTING & PARTICIPANTS: 6 stable long-term hemodialysis patients. INTERVENTION: Study participants underwent an experimental dialysis treatment in which K(o)A and Q(d) were increased by using 2 dialyzers in series and supplying each dialyzer with a Q(d) of 800 mL/min by using 2 dialysis machines. Experimental clearances were compared with those during a conventional treatment with a single dialyzer and Q(d) of 800 mL/min supplied by 1 machine. OUTCOMES: Measured clearances of uremic solutes. MEASUREMENTS: Clearances were measured for urea nitrogen and the bound solutes p-cresol sulfate, indoxyl sulfate, kynurenic acid, and hippurate. RESULTS: Clearances for the bound solutes during conventional treatment were lower than for urea nitrogen (clearance values: urea nitrogen, 255 +/- 16 mL/min; p-cresol sulfate, 23 +/- 4 mL/min; indoxyl sulfate, 30 +/- 7 mL/min; kynurenic acid, 43 +/- 4 mL/min; and hippurate, 115 +/- 11 mL/min). Experimental treatment increased clearances of all solutes (clearance values: urea nitrogen, 318 +/- 19 mL/min; p-cresol sulfate, 37 +/- 6 mL/min; indoxyl sulfate, 46 +/- 8 mL/min; kynurenic acid, 73 +/- 7 mL/min; and hippurate, 165 +/- 17 mL/min). The magnitude of the increases in clearance was greater for bound solutes than for urea nitrogen (increase in clearance: urea nitrogen, 25% +/- 6%; p-cresol sulfate, 66% +/- 19%; indoxyl sulfate, 57% +/- 27%; kynurenic acid, 69% +/- 5%; and hippurate, 44% +/- 15%). LIMITATIONS: A longer term study would be required to determine whether increased dialytic clearance of bound solutes leads to a decrease in plasma solute levels. CONCLUSIONS: Dialytic clearance of protein-bound solutes can be increased by increasing K(o)A and Q(d) to greater than conventional levels.