Optimizing Automated Peritoneal Dialysis Using an Extended 3-Pore Model

Abstract

Introduction: In the current study, an extended 3-pore model (TPM) is presented and applied to the problem of optimizing automated peritoneal dialysis (APD) with regard to osmotic water transport (UF), small/middle-molecule clearance, and glucose absorption.

Methods: Simulations were performed for either intermittent APD (IPD) or tidal APD (TPD). IPD was simulated for fill and drain volumes of 2 L, whereas TPD was simulated using a tidal volume of 0.5 L, 1 L, or 1.5 L with full drains and subsequent fills (2 L) occurring after every fifth dwell. A total of 25 cycles for a large number of different dialysate flow rates (DFR) were simulated using 3 different glucose concentrations (1.36%, 2.27%, and 3.86%) and 3 different peritoneal transport types: slow (peritoneal equilibrium test D/Pcrea < 0.6), fast (peritoneal equilibrium test D/Pcrea > 0.8), and average. Solute clearance and UF were simulated to occur during the entire dwell, including both fill and drain periods.

Results: It is demonstrated that DFRs exceeding ∼ 3 L/h are of little benefit both for UF and small-solute transport, whereas middle-molecule clearance is enhanced at higher DFRs. The simulations predict that large reductions (> 20%) in glucose absorption are possible by using moderately higher DFRs than a standard 6 × 2 L prescription and by using shorter optimized "bi-modal" APD regimens that alternate between a glucose-free solution and a glucose-containing solution.

Discussion: Reductions in glucose absorption appear to be significant with the proposed regimens for APD; however, further research is needed to assess the feasibility and safety of these regimens.

Keywords: 3-pore model; PD prescription; automated peritoneal dialysis; dialysis efficiency; urea kinetics.

Figures

Figure 1

Simulated urea clearances as a function of dialysate flow rate (DFR) for the different techniques: intermittent peritoneal dialysis (IPD) and tidal peritoneal dialysis 75%, 50%, and 25% (TPD75/50/25); different transport types: fast (red line), average (black line), and slow (blue line); and 3 different glucose concentrations: 1.36% (dotted line), 2.27% (solid line), and 3.86% (dashed line).

Figure 2

Osmotic water transport (ultrafiltration [UF]) per session hour as a function of dialysate flow rate (DFR) for the different techniques: intermittent peritoneal dialysis (IPD) and tidal peritoneal dialysis 75%, 50%, and 25% (TPD75/50/25); different transport types: fast (red line), average (black line), and slow (blue line); and 3 different glucose concentrations: 1.36% (dotted line), 2.27% (solid line), and 3.86% (dashed line).

Figure 3

Osmotic water transport (ultrafiltration [UF]) in milliliters per gram of glucose absorbed (or “UF efficiency”) plotted as a function of dialysate flow rate (DFR) for the different techniques: intermittent peritoneal dialysis (IPD) and tidal peritoneal dialysis 75%, 50%, and 25% (TPD75/50/25); different transport types: fast (red line), average (black line), and slow (blue line); and 3 different glucose concentrations: 1.36% (dotted line), 2.27% (solid line), and 3.86% (dashed line).

Figure 4

The small-solute transport efficiency (in millimoles [mmol] of urea removed per gram of glucose absorbed) as a function of dialysate flow rate (DFR) for the different techniques: intermittent peritoneal dialysis (IPD) and tidal peritoneal dialysis 75%, 50%, and 25% (TPD75/50/25); different transport types: fast (red line), average (black line), and slow (blue line); and 3 different glucose concentrations: 1.36% (dotted line), 2.27% (solid line), and 3.86% (dashed line).

Figure 5

Clearance of β2-microglobulin as a function of dialysate flow rate (DFR) for the different techniques: intermittent peritoneal dialysis (IPD) and tidal peritoneal dialysis 75%, 50%, and 25% (TPD75/50/25); different transport types: fast (red line), average (black line), and slow (blue line); and 3 different glucose concentrations: 1.36% (dotted line), 2.27% (solid line), and 3.86% (dashed line).

Figure 6

Osmotic water transport (ultrafiltration [UF]) in milliliters per liter of dialysis fluid “consumed” as a function of dialysate flow rate (DFR) for the different techniques, transport types, and glucose concentrations.

Figure 7

Simulated scenarios in which each dwell is optimized for either ultrafiltration (UF) (short dwells using 3.86% glucose) or small-solute transport (long dwells using 0% glucose) keeping the glucose absorption (abs) low. Corresponding transport parameters are shown in Table 4. Additional examples can be found in Supplementary Figures S1 and S2.

Figure S1

Optimized “bimodal” regimens using 5% glucose concentration. Simulated scenarios where each dwell is optimized for either UF (short dwells using 5% glucose) or small-solute transport (long dwells using 0% glucose) keeping the glucose absorption low. A reduction of up to 27% of the glucose absorption was obtained compared to the “standard prescription” (see Table 4).

Figure S2

Optimized “bimodal regimens using 6% glucose concentration. Simulated scenarios where each dwell is optimized for either UF (short dwells using 6% glucose) or small-solute transport (long dwells using 0% glucose) keeping the glucose absorption low. A reduction of up to 33% was attained.