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Quantifying the Effect of Changes in the Hemodialysis Prescription on Effective Solute Removal with a Mathematical Model

WILLIAM R. CLARK^*,, JOHN K. LEYPOLDT, LEE W. HENDERSON^*, BRUCE A. MUELLER^§, MERI KAY SCOTT^§ and EDWARD F. VONESH^*

^* Renal Division, Baxter Healthcare Corporation, McGaw Park, Illinois
Nephrology Division, Indiana University School of Medicine, Indianapolis, Indiana
Nephrology Division, University of Utah School of Medicine and Renal Section, Veterans Affairs Medical Center, Salt Lake City, Utah
^§ Department of Pharmacy Practice, Purdue University School of Pharmacy, West Lafayette, Indiana.

Correspondence to Dr. William R. Clark, Renal Division, Baxter Healthcare Corp., 1620 Waukegan Road, MPR-A2N, McGaw Park, IL 60085. Phone: 847-473-6583; Fax: 847-473-6902; E-mail: clarkbi{at}baxter.com

Abstract. One potential benefit of chronic hemodialysis (HD) regimens of longer duration or greater frequency than typical three-times-weekly schedules is enhanced solute removal over a relatively wide molecular weight spectrum of uremic toxins. This study assesses the effect of variations in HD frequency (F: per week), duration (T: min per treatment), and blood/dialysate flow rates (Q_B/Q_D: ml/min) on steady-state concentration profiles of five surrogates: urea (U), creatinine (Cr), vancomycin (V), inulin (I), and ß₂-microglobulin (ß2M). The regimens assessed for an anephric 70-kg patient were: A (standard): F = 3, T = 240, Q_B = 350, Q_D = 600; B (daily/short-time): F = 7, T = 100, Q_B = 350, Q_D = 600; C/D/E (low-flow/long-time): F = 3/5/7, T = 480, Q_B = 300, Q_D = 100. HD was simulated with a variable-volume double-pool model, which was solved by numerical integration (Runge-Kutta method). Endogenous generation rates (G) for U, Cr, and ß2M were 6.25, 1.0, and 0.17 mg/min, respectively; constant infusion rates for V and I of 0.2 and 0.3 mg/min, respectively, were used to simulate middle molecule (MM) G values. Intercompartment clearances of 600, 275, 125, 90, and 40 ml/min were used for U, Cr, V, I, and ß2M, respectively, For each solute/regimen combination, the equivalent renal clearance (EKR: ml/min) was calculated as a dimensionless value normalized to the regimen A EKR, which was 13.4, 10.8, 6.6, 3.7, and 4.8 ml/min for U, Cr, V, I, and ß2M, respectively. For regimens B, C, D, and E, respectively, these normalized EKR values were U: 1.04, 0.96, 1.58, and 2.22; Cr: 1.03, 1.08, 1.80, and 2.55; V: 1.06, 1.32, 2.21, and 3.12; I: 1.05, 1.54, 2.57, and 3.62; ß2M: 1.00, 1.27, 1.73, and 2.19. The extent of post-HD rebound (%) was highest for regimens A and B, ranging from 16% (urea) to 50% (inulin), and lowest for regimen E, ranging from 6% (urea) to 28% (ß2M). The following conclusions can be made: (1) Relative to a standard three-times-weekly HD regimen of approximately the same total (weekly) treatment duration, a daily/short-time regimen results in modest (3 to 6%) increases in effective small solute and MM removal. (2) Relative to a standard three-times-weekly HD regimen, a three-times-weekly low-flow/long-time regimen results in comparable effective small solute removal and progressive increases in MM and ß2M removal. A daily low-flow/long-time regimen substantially increases the effective removal of all solutes.

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