Pérez-García Rafael, Ramírez Chamond Rafael, de Sequera Ortiz Patricia, Albalate Marta, Puerta Carretero Marta, Ortega Mayra, Ruiz Caro M Caridad, Alcazar Arroyo Roberto
Servicio de Nefrología, Hospital Universitario Infanta Leonor, Madrid, España.
Departamento de Biología de Sistemas, Facultad de Medicina y Ciencias de la Salud Universidad de Alcalá, Alcalá de Henares (Madrid), España.
Nefrologia. 2017 Nov-Dec;37(6):630-637. doi: 10.1016/j.nefro.2017.03.024.
Increased acetataemia during haemodialysis sessions has been associated with a number of abnormalities, including increased oxidative stress, pro-inflammatory cytokines and nitric oxide synthesis. However, citric acid may play an alternative role to acetate as a dialysate stabiliser given that the effect of citrate on complement and leukocyte activation is different to that of acetate. The purpose of this study was to compare the inflammatory effect in immunocompetent blood cells of acetate dialysate and citrate dialysate.
The effect of acetate and/or citrate was investigated in the whole blood of uraemic patients and in healthy in vitro samples. Four types of dialysate were tested: dialysate 1, acetate-free with 1mmol/L of citrate; dialysate 2, with 0.8mmol/L of citrate and 0.3mmol/L of acetate; dialysate 3, citrate-free with 3mmol/L of acetate; and dialysate 4, citrate-free with 4mmol/L of acetate. The cell types used were: human monocyte culture (THP-1); and peripheral blood mononuclear cells (PBMCs) from healthy subjects and uraemic patients on haemodialysis. ICAM-1 was determined and levels of reactive oxygen species and total microvesicles were quantified.
Unlike the citrate dialysates, the dialysates with acetate (dialysate 3 and dialysate 4) induced increased ICAM-1 expression density in THP-1 cells; an increase in ICAM-1 expression was observed in the immunocompetent cells of healthy subjects with acetate dialysate (dialysate 3 and dialysate 4) but not with citrate dialysate (dialysate 1 and dialysate 2). No significant ICAM-1 differences were found between the different dialysates in the cells of haemodialysed patients. Reactive oxygen species expression and the number of microvesicles increased significantly with acetate dialysate but not with citrate dialysate in the cells of both healthy subjects and haemodialysed patients.
At the concentrations in which it is generally used in clinical practice, acetate-based dialysate increases oxidative stress and the total number of microvesicles and may induce other pro-inflammatory stimuli typical of uraemic patients on haemodialysis. Citrate dialysates do not induce this activation, which could make them a suitable alternative in clinical practice.
血液透析过程中乙酸血症增加与多种异常情况相关，包括氧化应激增加、促炎细胞因子和一氧化氮合成增加。然而，鉴于柠檬酸盐对补体和白细胞激活的作用与乙酸盐不同，柠檬酸可能作为透析液稳定剂发挥与乙酸盐不同的作用。本研究的目的是比较乙酸盐透析液和柠檬酸盐透析液对免疫活性血细胞的炎症影响。
在尿毒症患者的全血和健康的体外样本中研究乙酸盐和/或柠檬酸盐的作用。测试了四种类型的透析液：透析液1，不含乙酸盐，含1mmol/L柠檬酸盐；透析液2，含0.8mmol/L柠檬酸盐和0.3mmol/L乙酸盐；透析液3，不含柠檬酸盐，含3mmol/L乙酸盐；透析液4，不含柠檬酸盐，含4mmol/L乙酸盐。使用的细胞类型为：人单核细胞培养物（THP-1）；以及来自健康受试者和接受血液透析的尿毒症患者的外周血单核细胞（PBMC）。测定细胞间黏附分子-1（ICAM-1），并对活性氧物质水平和总微泡进行定量。
与柠檬酸盐透析液不同，含乙酸盐的透析液（透析液3和透析液4）可诱导THP-1细胞中ICAM-1表达密度增加；在使用乙酸盐透析液（透析液3和透析液4）的健康受试者的免疫活性细胞中观察到ICAM-1表达增加，而使用柠檬酸盐透析液（透析液1和透析液2）时未观察到。在接受血液透析患者的细胞中，不同透析液之间未发现ICAM-1有显著差异。在健康受试者和接受血液透析患者的细胞中，乙酸盐透析液可使活性氧物质表达和微泡数量显著增加，而柠檬酸盐透析液则不会。
在临床实践中通常使用的浓度下，基于乙酸盐的透析液会增加氧化应激和微泡总数，并可能诱导血液透析的尿毒症患者出现其他典型的促炎刺激。柠檬酸盐透析液不会诱导这种激活，这可能使其成为临床实践中的合适替代方案。
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