Icodextrin degradation products in spent dialysate of CAPD patients and the rat, and its relation with dialysate osmolality

. Objective: Peritoneal dialysis (PD) with a 7.5% icodextrin-containing dia lysis solution provides prolonged ultrafiltration compared with glucose-bas ed dialysis solutions. Colloid osmosis is the most likely mechanism, but st udies in rats suggest it is caused by an increase in osmolality due to degr adation of icodextrin. Therefore, human spent dialysate was analyzed with h igh-performance liquid chromatography (HPLC) using gel permeation size-excl usion chromatography. An increasing peak (with a low molecular weight, < 10 00 Dal was observed during the dwell. The aim of this study was to quantita te breakdown products of icodextrin (which could explain this peak) and inv estigate whether there was a relationship with dialysate amylase concentrat ion and dialysate osmolality. . Design: Long-dwell effluents (dwell time 9.15 - 14.30 hours) obtained fro m 12 PD patients using a 7.5% icodextrin solution during the night were ana lyzed. The following icodextrin breakdown products were measured: maltotetr aose (G4), maltotriose (G3), maltose (G2), and glucose (G1). In 6 of these patients, the sugars maltoheptaose (G7), maltohexaose (G6), and maltopentao se (G5) were also determined in both effluent and plasma. In addition, G4, G3, G2, and G1 were measured in four Wistar rats during a B-hour dwell stud y. . Results: In the human studies, the median distribution of the sugars in t he effluent was G4, 8.7%; G3, 16.5%; G2, 23.1%; and G1, 53.5%. The osmolali ty in spent dialysate ranged between 288 and 326 mOsm/kg H2O. The median co ntribution of the sugars G2 - G4 was 5.4 mOsm/kg H2O. No correlation was pr esent 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 dura tion of the dwell (r = 0.50, p = 0.10). No relationship was found between t he 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 th e 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 osmo lality in the spent dialysate (r = 0.92, p < 0.0001). The levels of the sug ars G2, G3, and G4 in effluent were higher than in unused dialysate, but lo wer 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 t han in plasma. In the rat study, dialysate osmolality increased with the du ration of the dwell. A clear relationship was present between osmolality an d concentration of the sugars G2 - G4 in the effluent. The median amount of amylase in the effluent was 1252 U/L. . Conclusion: A 7.5% icodextrin-based dialysis solution used during the lon g exchange caused only a slight increase in dialysate osmolality in humans. The osmolality at the end of the dwell in the human situation was dependen t mainly on concentrations of the small solutes urea and sodium in the effl uent. The contribution of icodextrin degradation products was marginal. In the rat, however, a dear relationship was present between osmolality and ic odextrin degradation products in spent dialysate, explaining the increased dialysate osmolality at the end of the dwell. The difference between the tw o species can be explained by the very high amylase concentrations in the r at, leading to a rapid degradation of icodextrin. The rat is therefore not suitable to study peritoneal fluid kinetics using icodextrin as an osmotic agent.