Icodextrin Degradation Products in Spent Dialysate of CAPD Patients and the Rat, and its Relation with Dialysate Osmolality

Abstract

ObjectivePeritoneal dialysis (PD) with a 7.5% icodextrin-containing dialysis solution provides prolonged ultra-filtration compared with glucose-based dialysis solutions. Colloid osmosis is the most likely mechanism, but studies in rats suggest it is caused by an increase in osmolality due to degradation of icodextrin. Therefore, human spent dialysate was analyzed with high-performance liquid chromatography (HPLC) using gel permeation size-exclusion chromatography. An increasing peak (with a low molecular weight, < 1000 Da) was observed during the dwell. The aim of this study was to quantitate breakdown products of icodextrin (which could explain this peak) and investigate whether there was a relationship with dialysate amylase concentration and dialysate osmolality.DesignLong-dwell effluents (dwell time 9.15 – 14.30 hours) obtained from 12 PD patients using a 7.5% ico-dextrin solution during the night were analyzed. The following icodextrin breakdown products were measured: maltotetraose (G4), maltotriose (G3), maltose (G2), and glucose (G1). In 6 of these patients, the sugars maltoheptaose (G7), maltohexaose (G6), and maltopentaose (G5) were also determined in both effluent and plasma. In addition, G4, G3, G2, and G1 were measured in four Wistar rats during a 6-hour dwell study.ResultsIn the human studies, the median distribution of the sugars in the effluent was G4, 6.7%; G3, 16.5%; G2, 23.1%; and G1, 53.5%. The osmolality in spent dialysate ranged between 288 and 326 mOsm/kg H2O. The median contribution of the sugars G2 – G4 was 5.4 mOsm/kg H2O. No correlation was present between dialysate osmolality and duration of the dwell ( r = –0.04, p = 0.91); nor was there a relation between the concentration of G2 and duration of the dwell ( r = 0.50, p = 0.10). No relationship was found between the amount of amylase and the concentration of G2 in the effluent ( r = 0.49, p = 0.10), nor between the total concentration of the sugars G2 – G4 in the spent dialysate and dialysate osmolality ( r = –0.31, p = 0.33). However, a strong correlation was seen between urea concentration and osmolality ( r = 0.85, p < 0.001), and also between sodium concentration and dialysate osmolality in the spent dialysate ( r = 0.92, p < 0.0001). The levels of the sugars G2, G3, and G4 in effluent were higher than in unused dialysate, but lower than or similar to plasma levels. Concentrations of the sugars G5, G6, and G7 were lower in spent dialysate than in unused dialysate, and higher than in plasma. In the rat study, dialysate osmolality increased with the duration of the dwell. A clear relationship was present between osmolality and concentration of the sugars G2 – G4 in the effluent. The median amount of amylase in the effluent was 1252 U/L.ConclusionA 7.5% icodextrin-based dialysis solution used during the long exchange caused only a slight increase in dialysate osmolality in humans. The osmolality at the end of the dwell in the human situation was dependent mainly on concentrations of the small solutes urea and sodium in the effluent. The contribution of icodextrin degradation products was marginal. In the rat, however, a clear relationship was present between osmolality and icodextrin degradation products in spent dialysate, explaining the increased dialysate osmolality at the end of the dwell. The difference between the two species can be explained by the very high amylase concentrations in the rat, leading to a rapid degradation of icodextrin. The rat is therefore not suitable to study peritoneal fluid kinetics using icodextrin as an osmotic agent.