Modelling of icodextrin hydrolysis and kinetics during peritoneal dialysis

Area of Science:

• Nephrology
• Biomedical Engineering
• Pharmacokinetics

Background:

• Peritoneal dialysis (PD) relies on osmotic agents for ultrafiltration.
• Icodextrin solutions are used in PD, but their polysaccharide chains can degrade via alpha-amylase activity in dialysate.
• This degradation affects the osmotic properties and efficacy of icodextrin during PD exchanges.

Purpose of the Study:

• To model water and solute removal during peritoneal dialysis with icodextrin.
• To investigate the impact of alpha-amylase-mediated icodextrin degradation and absorption on PD kinetics.
• To extend the three-pore model to incorporate icodextrin hydrolysis by alpha-amylase.

Main Methods:

• Collected data from 11 patients during 16-hour dwells with icodextrin solution.
• Analyzed dialysate volume, concentrations of glucose, urea, creatinine, alpha-amylase, and seven icodextrin fractions.
• Extended the three-pore model to include icodextrin hydrolysis and absorption kinetics.

Main Results:

• The extended three-pore model accurately predicted ultrafiltration, small solute, and icodextrin fraction kinetics.
• Observed differences in icodextrin degradation kinetics between icodextrin-naïve and icodextrin-exposed patients.
• The model provided insights into icodextrin degradation patterns influenced by alpha-amylase activity.

Conclusions:

• The developed model accurately describes peritoneal transport during long icodextrin dwells.
• Accounting for icodextrin absorption and alpha-amylase activity is crucial for accurate PD modeling.
• The study highlights the influence of patient history (icodextrin exposure) on icodextrin degradation kinetics.