de Waart D R, Zweers M M, Struijk D G, Krediet R T
Department of Clinical Chemistry, University of Amsterdam, The Netherlands.
Perit Dial Int. 2001 May-Jun;21(3):269-74.
Peritoneal dialysis (PD) with a 7.5% icodextrin-containing dialysis solution provides prolonged ultrafiltration 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.
Long-dwell effluents (dwell time 9.15- 14.30 hours) obtained from 12 PD patients using a 7.5% icodextrin 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.
In 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.
A 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.
与基于葡萄糖的透析液相比，含7.5%艾考糊精的透析液进行腹膜透析（PD）可提供更长时间的超滤。胶体渗透是最可能的机制，但大鼠研究表明这是由于艾考糊精降解导致渗透压升高所致。因此，使用凝胶渗透尺寸排阻色谱的高效液相色谱（HPLC）对人体用过的透析液进行了分析。在停留期间观察到一个峰增加（分子量低，<1000 Da）。本研究的目的是对艾考糊精的分解产物进行定量（这可以解释该峰），并研究其与透析液淀粉酶浓度和透析液渗透压之间是否存在关系。
分析了12例PD患者夜间使用7.5%艾考糊精溶液获得的长时间停留流出液（停留时间9.15 - 14.30小时）。测量了以下艾考糊精分解产物：麦芽四糖（G4）、麦芽三糖（G3）、麦芽糖（G2）和葡萄糖（G1）。在其中6例患者中，还测定了流出液和血浆中的麦芽七糖（G7）、麦芽六糖（G6）和麦芽五糖（G5）。此外，在一项6小时停留研究中对4只Wistar大鼠的G4、G3、G2和G1进行了测量。
在人体研究中，流出液中糖的中位数分布为：G4，6.7%；G3，16.5%；G2，23.1%；G1，53.5%。用过的透析液渗透压在288至326 mOsm/kg H2O之间。糖G2 - G4的中位数贡献为5.4 mOsm/kg H2O。透析液渗透压与停留时间之间无相关性（r = -0.04，p = 0.91）；G2浓度与停留时间之间也无关系（r = 0.50，p = 0.10）。未发现淀粉酶量与流出液中G2浓度之间的关系（r = 0.49，p = 0.10），也未发现用过的透析液中糖G2 - G4的总浓度与透析液渗透压之间的关系（r = -0.31，p = 0.33）。然而，尿素浓度与渗透压之间存在强相关性（r = 0.85，p < 0.001），用过的透析液中钠浓度与透析液渗透压之间也存在强相关性（r = 0.92，p < 0.0001）。流出液中G2、G3和G4的水平高于未使用的透析液，但低于或类似于血浆水平。用过的透析液中G5、G6和G7的浓度低于未使用的透析液，且高于血浆。在大鼠研究中，透析液渗透压随停留时间增加。渗透压与流出液中糖G2 - G4的浓度之间存在明显关系。流出液中淀粉酶的中位数为1252 U/L。
长时间交换期间使用的7.5%艾考糊精基透析液在人体中仅使透析液渗透压略有增加。人体情况下停留结束时的渗透压主要取决于流出液中小溶质尿素和钠的浓度。艾考糊精降解产物的贡献很小。然而，在大鼠中，用过的透析液渗透压与艾考糊精降解产物之间存在明显关系，这解释了停留结束时透析液渗透压的增加。两种物种之间的差异可以通过大鼠中非常高的淀粉酶浓度来解释，这导致艾考糊精快速降解。因此，大鼠不适合用于研究以艾考糊精作为渗透剂的腹膜液动力学。
