Modelling of icodextrin hydrolysis and kinetics during peritoneal dialysis

In peritoneal dialysis, ultrafiltration is achieved by adding an osmotic agent into the dialysis fluid. During an exchange with icodextrin-based solution, polysaccharide chains are degraded by alpha-amylase activity in dialysate, influencing its osmotic properties. We modelled water and solute removal taking into account degradation by alpha-amylase and absorption of icodextrin from the peritoneal cavity. Data from 16 h dwells with icodextrin-based solution in 11 patients (3 icodextrin-exposed, 8 icodextrin-naive at the start of the study) on dialysate volume, dialysate concentrations of glucose, urea, creatinine and alpha-amylase, and dialysate and blood concentrations of seven molecular weight fractions of icodextrin were analysed. The three-pore model was extended to describe hydrolysis of icodextrin by alpha-amylase. The extended model accurately predicted kinetics of ultrafiltration, small solutes and icodextrin fractions in dialysate, indicating differences in degradation kinetics between icodextrin-naive and icodextrin-exposed patients. In addition, the model provided information on the patterns of icodextrin degradation caused by alpha-amylase. Modelling of icodextrin kinetics using an extended three-pore model that takes into account absorption of icodextrin and changes in alpha-amylase activity in the dialysate provided accurate description of peritoneal transport and information on patterns of icodextrin hydrolysis during long icodextrin dwells.