Optimization of bimodal automated peritoneal dialysis prescription using the three-pore model

Abstract

Background: Previous studies suggested that automated peritoneal dialysis (APD) could be improved in terms of shorter treatment times and lower glucose absorption using bimodal treatment regimens, having ‘ultrafiltration (UF) cycles’ using a high glucose concentration and ‘clearance cycles’ using low or no glucose. The purpose of this study is to explore such regimes further using mathematical optimization techniques based on the three-pore model. Methods: A linear model with constraints is applied to find the shortest possible treatment time given a set of clinical treatment goals. For bimodal regimes, an exact analytical solution often exists which is herein used to construct optimal regimes giving the same Kt/ V urea and/or weekly creatinine clearance and UF as a 6 × 2 L 1.36% glucose regime and an ‘adapted’ (2 × 1.5 L 1.36% + 3 × 3 L 1.36%) regime. Results: Compared to the non-optimized (standard and adapted regimes), the optimized regimens demonstrated marked reductions (>40%) in glucose absorption while having an identical weekly creatinine clearance (35 L) and UF (0.5 L). Larger fill volumes of 1200 mL/m2 (UF cycles) and 1400 mL/m2 (clearance cycles) can be used to shorten the total treatment time. Conclusion: These theoretical results imply substantial improvements in glucose absorption using optimized APD regimens while achieving similar water and solute removal as non-optimized APD regimens. While the current results are based on a well-established theoretical model for peritoneal dialysis, experimental and clinical studies need to be performed to validate the current findings.

Dual SGLT1/SGLT2 inhibitor phlorizin reduces glucose transport in experimental peritoneal dialysis

“…Several techniques have been proposed to reduce glucose absorption during glucose-based PD, such as icodextrin, 1 alternate PD fluids 2 or by altering the prescription. 3 –6…”

“…Several techniques have been proposed to reduce glucose absorption during glucose-based PD, such as icodextrin, 1 alternate PD fluids 2 or by altering the prescription. [3][4][5][6] Glucose is a polar compound and is therefore impermeable across cell membranes. In the small intestine, SGLT1 transporters mediate nearly all sodium dependent glucose and galactose uptake (1 Na þ for each glucose molecule) but has only a minor role in kidney glucose handling.…”

Optimised versus standard automated peritoneal dialysis regimens pilot study (OptiStAR): A randomised controlled crossover trial

“…Optimised regimens refer to the concept of targeting ultrafiltration and small solute removal separately by prescribing APD treatments with altering dwells components and durations. 22 In this study, we evaluated a prescription combining ultra-low and high glucose cycles (clearance and UF cycles) according to a pre-study computer-aided prescription on the basis of the extended TPM. 19 Simulations predicted a reduction in absorbed glucose of 10 g during conditions in which the amount of UF and small solute clearance is the same in both regimes.…”

“…The limited sample size will inflate type 2 error rates, meaning that non-significant results should be interpreted carefully. The concept of optimised APD 19,22 refers to mathematically optimised multi-cycle regimens tailored to the individual patient’s needs (e.g. in terms of UF target or small solute transport).…”

Modelling of icodextrin hydrolysis and kinetics during peritoneal dialysis

“…In particular, similar values of ultrafiltration coefficient, LpS, estimated in our Ico+ group were found by Galach et al (0.048 mL/min/mmHg) and by Vonesh et al using PD Adequest v. 2.0 (0.045 mL/min/mmHg) 2,16 . In the simulations described in the present study, a higher value of peritoneal absorption rate, based on the marker elimination rate from the peritoneal cavity, was used instead of that often assumed for 3PM 10,12,17,26,[33][34][35] . In the study by Rippe and Levin, followed by Akonur et al and Morelle et al, a value of 0.3 mL/min was used, a value that is much lower than the value, typically around 1 mL/min, as measured using a volume marker 12,14,17 .…”