van Westrhenen Roos, Vlijm Anniek, Hiralall Johan K, Krediet Raymond T
Department of Nephrology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Perit Dial Int. 2008 Nov;28 Suppl 5:S43-7.
Chronic exposure to glucose and glucose degradation products (GDPs) in dialysis solutions is involved in the pathogenesis of peritoneal neoangiogenesis and fibrosis, potentially leading to encapsulating peritoneal sclerosis (EPS). High lactate concentrations may contribute to glucose toxicity by creating a state of pseudohypoxia, which stimulates the formation of various growth factors.
To study the effects of long-term peritoneal exposure to a filter-sterilized pyruvate-buffered solution with a combination of 3 osmotic agents (amino acids, glycerol, glucose: PYRAGG) on peritoneal function and morphology.
Rats were exposed daily for a period of 20 weeks to PYRAGG, or to a conventional heat-sterilized solution (LH), or to a filter-sterilized solution (LF), after which a peritoneal function test was done and peritoneal tissue was obtained.
Peritoneal solute and fluid transport characteristics at 20 weeks were similar in all groups. Fibrosis was most pronounced in the LH group compared to the others, suggesting an effect of GDPs. A marked reduction in the number of omental vessels was noted in the PYRAGG group (59% reduction compared to LH). A modest reduction (28%) was found in the LF animals. This points to a marked effect of reduced exposure to glucose.
PYRAGG was more biocompatible than a filter-sterilized glucose/lactate solution because it did not induce marked peritoneal abnormalities after long-term exposure. This did not lead to altered peritoneal transport characteristics. It is likely that further development of PYRAGG-like solutions will decrease the incidence of EPS.
透析液中长期暴露于葡萄糖和葡萄糖降解产物(GDPs)参与腹膜新生血管形成和纤维化的发病机制,可能导致包裹性腹膜硬化(EPS)。高乳酸浓度可能通过产生假缺氧状态促进葡萄糖毒性,从而刺激各种生长因子的形成。
研究长期腹膜暴露于含3种渗透剂(氨基酸、甘油、葡萄糖:PYRAGG)组合的过滤除菌丙酮酸缓冲溶液对腹膜功能和形态的影响。
大鼠每日暴露于PYRAGG、传统热消毒溶液(LH)或过滤除菌溶液(LF)20周,之后进行腹膜功能测试并获取腹膜组织。
20周时所有组的腹膜溶质和液体转运特征相似。与其他组相比,LH组纤维化最为明显,提示GDPs的作用。PYRAGG组网膜血管数量显著减少(与LH组相比减少59%)。LF组动物有适度减少(28%)。这表明减少葡萄糖暴露有显著作用。
PYRAGG比过滤除菌的葡萄糖/乳酸溶液生物相容性更好,因为长期暴露后它不会引起明显的腹膜异常。这并未导致腹膜转运特征改变。类似PYRAGG溶液的进一步研发可能会降低EPS的发生率。