Linnæus Center for Biomaterials Chemistry , Linnæus University , Kalmar , Sweden.
Linnæus Center for Biomaterials Chemistry , Linnæus University , Kalmar , Sweden ; Department of Immunology, Genetics and Pathology (IGP), Rudbeck Laboratory C5:3 , Uppsala University , Uppsala , Sweden.
Clin Kidney J. 2015 Feb;8(1):31-7. doi: 10.1093/ckj/sfu127. Epub 2014 Dec 1.
The use of acetate in haemodialysis fluids may induce negative effects in patients including nausea and increased inflammation. Therefore, haemodialysis fluids where acetate is substituted with citrate have recently been developed. In this study, we investigated the biocompatibility of citrate employing concentrations used in haemodialysis.
The effects of citrate and acetate were investigated in human whole blood in vitro under conditions promoting biomaterial-induced activation. Complement activation was measured as generation of C3a, C5a and the sC5b-9 complex, and granulocyte activation as up-regulation of CD11b expression. For the experimental set-up, a mathematical model was created to calculate the concentrations of acetate and citrate attained during haemodialysis.
Citrate reduced granulocyte activation and did not induce higher complement activation compared with acetate at concentrations attained during haemodialysis. Investigating different citrate concentrations clearly showed that citrate is a potent complement inhibitor already at low concentrations, i.e. 0.25 mM, which is comparable with concentrations detected in the blood of patients during dialysis with citrate-containing fluids. Increased citrate concentration up to 6 mM further reduced the activation of C3a, C5a and sC5b-9, as well as the expression of CD11b.
Our results suggest that citrate is a promising substitute for acetate for a more biocompatible dialysis, most likely resulting in less adverse effects for the patients.
在血液透析液中使用醋酸盐可能会给患者带来负面影响，包括恶心和炎症增加。因此，最近已经开发出用柠檬酸盐替代醋酸盐的血液透析液。在这项研究中，我们研究了柠檬酸盐的生物相容性，使用了血液透析中使用的浓度。
在促进生物材料诱导激活的体外条件下，研究了柠檬酸盐和醋酸盐对人全血的影响。通过生成 C3a、C5a 和 sC5b-9 复合物来测量补体激活，通过上调 CD11b 表达来测量粒细胞激活。对于实验设置，创建了一个数学模型来计算血液透析过程中获得的醋酸盐和柠檬酸盐的浓度。
与醋酸盐相比，柠檬酸盐在血液透析过程中获得的浓度下降低了粒细胞激活，并且不会引起更高的补体激活。研究不同的柠檬酸盐浓度清楚地表明，柠檬酸盐已经是一种有效的补体抑制剂，即使在低浓度下，即 0.25mM，这与含柠檬酸盐的透析液中患者血液中的浓度相当。增加至 6mM 的柠檬酸浓度进一步降低了 C3a、C5a 和 sC5b-9 的激活以及 CD11b 的表达。
我们的结果表明，柠檬酸盐是一种有前途的醋酸盐替代品，可实现更生物相容的透析，很可能会减少患者的不良反应。
