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Increasing the Clearance of Protein-Bound Solutes by Addition of a Sorbent to the Dialysate

Timothy W. Meyer^*, John W.T. Peattie^*, Jared D. Miller^*, Diana C. Dinh^*, Natalie S. Recht^*, Jason L. Walther^* and Thomas H. Hostetter

^* Departments of Medicine, VA Palo Alto HCS and Stanford University, Palo Alto, California; and Department of Medicine, Albert Einstein College of Medicine, New York, New York

Address correspondence to: Dr. Timothy W. Meyer, Nephrology 111R, Palo Alto VAHCS, 3801 Miranda Avenue, Palo Alto, CA 94303. Phone: 650-852-3314; Fax: 650-852-3411; twmeyer{at}stanford.edu

Received for publication August 15, 2006. Accepted for publication December 4, 2006.

The capacity of sorbent systems to increase solute clearances above the levels that are provided by hemodialysis has not been well defined. This study assessed the extent to which solute clearances can be increased by addition of a sorbent to the dialysate. Attention was focused on the clearance of protein-bound solutes, which are cleared poorly by conventional hemodialysis. A reservoir that contained test solutes and artificial plasma was dialyzed first with the plasma flow set at 46 ± 3 ml/min and the dialysate flow (Q_d) set at 42 ± 3 ml/min using a hollow fiber kidney with mass transfer area coefficients greater than Q_d for each of the solutes. Under these conditions, the clearance of urea (Cl_urea) was 34 ± 1 ml/min, whereas the clearances of the protein-bound solutes indican (Cl_ind), p-cresol sulfate (Cl_pcs), and p-cresol (Cl_pc) averaged only 5 ± 1, 4 ± 1, and 14 ± 1 ml/min, respectively The effect of addition of activated charcoal to the dialysate then was compared with the effect of increasing Q_d without addition of any sorbent. Addition of charcoal increased Cl_ind, Cl_pcs, and Cl_pc to 12 ± 1, 9 ± 2, and 35 ± 4 ml/min without changing Cl_urea. Increasing Q_d without the addition of sorbent had a similar effect on the clearance of the protein-bound solutes. Mathematical modeling predicted these changes and showed that the maximal effect of addition of a sorbent to the dialysate is equivalent to that of an unlimited increase in Q_d. These results suggest that as an adjunct to conventional hemodialysis, addition of sorbents to the dialysate could increase the clearance of protein-bound solutes without greatly altering the clearance of unbound solutes.

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