Contribution of residual function to removal of protein-bound solutes in hemodialysis.

BACKGROUND AND OBJECTIVES: This study evaluated the contribution of residual function to the removal of solutes for which protein binding limits clearance by hemdialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Solute concentrations were measured in 25 hemodialysis patients with residual urea clearances ranging from 0.1 to 6.2 ml/min per 1.73 m2. Mathematical modeling assessed the effect of residual function on time-averaged solute concentrations. RESULTS: Dialytic clearances of the protein-bound solutes p-cresol sulfate, indoxyl sulfate, and hippurate were reduced in proportion to the avidity of binding and averaged 8±2, 10±3, and 44±13% of the dialytic urea clearance. For each bound solute, the residual clearance was larger in relation to the residual urea clearance. Residual kidney function therefore removed a larger portion of each of the bound solutes than of urea. Increasing residual function was associated with lower plasma levels of p-cresol sulfate and hippurate but not indoxyl sulfate. Wide variation in solute generation tended to obscure the dependence of plasma solute levels on residual function. Mathematical modeling that corrected for this variation indicated that increasing residual function will reduce the plasma level of each of the bound solutes more than the plasma level of urea. CONCLUSIONS: In comparison to urea, solutes than bind to plasma proteins can be more effectively cleared by residual function than by hemodialysis. Levels of such solutes will be lower in patients with residual function than in patients without residual function even if the dialysis dose is reduced based on measurement of residual urea clearance in accord with current guidelines.

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.