Institut National de la Transfusion Sanguine, UFR Médecine, Paris, France.
Perit Dial Int. 2006 Nov-Dec;26(6):664-70.
Conventional peritoneal dialysis fluids (PDFs) have been shown to damage the mesothelial layer and are associated with the development of peritoneal fibrosis and neoangiogenesis. New-generation PDFs have therefore been developed with physiological pH and reduced levels of glucose degradation products (GDPs), precursors of advanced glycation end products (AGEs). In this work, we evaluated and compared the improved biocompatibility of two new-generation PDFs (Balance and bicaVera) using mesothelial cell biology; we also compared them to a standard PDF (stay.safe) (all PDFs by Fresenius Medical Care, Fresnes, France).
stay.safe, Balance, and bicaVera were tested for their effect on human peritoneal mesothelial cell (HPMC) viability by measuring cell proliferation and apoptosis, and oncosis induction. The formation of AGEs was evaluated by immunoassay. Transforming growth factor beta-1 and vascular endothelial growth factor (VEGF) were immunoassayed in HPMC supernatants exposed to the above PDFs.
At 15 g/L glucose concentration, HPMC exposure to bicaVera resulted in higher cell proliferation compared to Balance (p < 0.001) and stay.safe (p < 0.001). Compared to the lactate-buffered PDFs (Balance and stay.safe), oncosis was significantly lower in cells exposed to bicaVera (p < 0.05). bicaVera, containing lower amounts of GDPs, generated less AGE formation (p < 0.05) and VEGF production (p < 0.05) than either Balance or stay.safe.
New-generation PDFs with physiological pH and lower GDP levels, especially if bicarbonate-buffered (bicaVera), have fewer in vitro toxic effects on mesothelial cells and may contribute to peritoneal preservation, thus improving long-term treatment of PD patients.
已证实传统腹膜透析液(PDF)会损伤间皮细胞层,并与腹膜纤维化和新生血管形成的发展有关。因此,新一代 PDF 已被开发出来,具有生理 pH 值和降低的葡萄糖降解产物(GDP)水平,GDP 是晚期糖基化终产物(AGE)的前体。在这项工作中,我们使用间皮细胞生物学评估和比较了两种新一代 PDF(Balance 和 bicaVera)的改善的生物相容性;我们还将它们与标准 PDF(stay.safe)进行了比较(所有 PDF 均由 Fresenius Medical Care,法国弗雷讷)。
通过测量细胞增殖和凋亡以及诱导细胞胀亡来测试 stay.safe、Balance 和 bicaVera 对人腹膜间皮细胞(HPMC)活力的影响。通过免疫测定法评估 AGE 的形成。暴露于上述 PDF 的 HPMC 上清液中测定转化生长因子β-1 和血管内皮生长因子(VEGF)。
在 15 g/L 葡萄糖浓度下,与 Balance(p < 0.001)和 stay.safe(p < 0.001)相比,HPMC 暴露于 bicaVera 导致更高的细胞增殖。与乳酸盐缓冲的 PDF(Balance 和 stay.safe)相比,暴露于 bicaVera 的细胞的胀亡明显更低(p < 0.05)。含 GDP 量较低的 bicaVera 产生的 AGE 形成(p < 0.05)和 VEGF 产生(p < 0.05)均低于 Balance 或 stay.safe。
具有生理 pH 值和较低 GDP 水平的新一代 PDF,尤其是如果是碳酸氢盐缓冲的(bicaVera),对间皮细胞的体外毒性作用较小,可能有助于腹膜保存,从而改善 PD 患者的长期治疗效果。