#3270 TRANSPORT AND HYDROLYSIS OF ICODEXTRIN DURING PERITONEAL DIALYSIS
Authors: Stachowska-Pietka Joanna , Waniewski Jacek , Olszowska Anna , Garcia-Lopez Elvia , Wankowicz Zofia , Lindholm Bengt 
Published: June 2023

Abstract

Background and Aims
α-amylase, an enzyme present in plasma and peritoneal tissue, takes part in the process of starch digestion. During peritoneal exchange with icodextrin-based solution, polysaccharide chains are hydrolysed to shorter oligosaccharide chains, influencing osmotic properties of peritoneal dialysate. We estimated peritoneal transport parameters and compared them with hydrolytic clearances using a new model that takes into consideration absorption of icodextrin from the peritoneal cavity and its degradation by α-amylase.

Method
Frequent dialysate and blood samples were taken in 11 patients (8 icodextrin-naïve, 3 icodextrin-exposed) undergoing 16-hour dwell studies with icodextrin-based dialysis solution and labeled serum albumin (RISA) added as a volume marker. Using data on the intraperitoneal volume and dialysate and blood concentrations of glucose, urea, creatinine, and 7 icodextrin molecular weight (MW) fractions (glucose polymer size classes) and dialysate concentrations of α-amylase the extended three-pore model was applied to estimate individual parameters related to the peritoneal transport induced by dialysis and to hydrolysis of icodextrin by α-amylase. The following MW cut-off values were assumed for icodextrin fractions: up to 1.08, 4.44, 9.89, 21.4, 43.5, 66.7 and over 66.7 kDa, called Fractions 1–7, respectively. The hydrolytic clearances were defined as rate at which dialysate volume is cleared of the fraction by hydrolysis. The time-dependent hydrolytic clearances of icodextrin fractions were calculated and compared with diffusive ones. For the first time the extended three-pore model was validated not only with respect to the peritoneal transport of water and small solutes but also regarding concentration of icodextrin fractions.

Results
Mean measured and simulated dialysate to plasma concentration ratios for glucose, urea and creatinine are presented in Figure 1, left panel. The peritoneal kinetic of icodextrin (dialysate concentrations of each fraction over its initial concentration) is presented for mean measured data and numerical simulation results in Figure 1, right panel. The results showed that the model provides accurate (mean relative error less than 7%) description of individual patient peritoneal transport kinetics including that of icodextrin fractions in peritoneal dialysate. The comparison of hydrolytic clearances (H) with diffusive transport parameters for icodextrin fractions (PS, reflecting the maximal rates of their clearance by diffusion) showed that in case of shorter polymers (Fractions 1–3) diffusive clearances were higher or similar to hydrolytic ones over the whole dwell time. In case of Fractions 4 and 5, the initial domination of PS slowly decreased during the dwell time, being dominated by hydrolysis processes at the end of the exchange, at least partly due to the changes of intraperitoneal volume and α-amylase concentration. In case of polysaccharides from Fractions 6 and 7, their hydrolytic clearances remained higher than the diffusive ones during whole dwell time. Interestingly, the obtained values of H in icodextrin-exposed patients typically remained below 1.2 mL/min except for Fraction 6, for which H increased from initial value of 0.83±0.30 to 1.43±0.64 mL/min at the end of the peritoneal dwell. On the other hand, the estimated final values of H in icodextrin-naïve patients were on average higher than 1.2 mL/min in all fractions except Fractions 4 and 5.

Conclusion
The model provided accurate description of peritoneal transport and icodextrin hydrolysis during long icodextrin dwells. The model showed that hydrolytic processes dominate over diffusive ones during whole dwell time in case of Fractions 6 and 7, whereas diffusive processes dominate for Fractions 1–3.