Bonomini Mario, Ballone Enzo, Di Stante Silvio, Bucciarelli Tonino, Dottori Secondo, Arduini Arduino, Urbani Andrea, Sirolli Vittorio
Institute of Nephrology and Biostatistical Laboratory, Department of Medicine, G. d'Annunzio University, SS Annunziata University Hospital, Via dei Vestini, 66013 Chieti, Italy.
Nephrol Dial Transplant. 2004 Jan;19(1):68-74. doi: 10.1093/ndt/gfg532.
Solute(s) retained during uraemia cause increased exposure of aminophospholipid phosphatidylserine (PS) on the outer surface of erythrocyte membranes, and this phenomenon may be involved in the pathophysiology of uraemia by promoting abnormal erythrocyte interactions.
We examined in a prospective randomized cross-over fashion the ability of various dialysis modalities to remove the circulating uraemic factor(s) causing increased PS externalization in red cells. Each patient was treated with haemodialysis (HD) and with on-line haemodiafiltration (HDF) using standard high-flux polysulphone membranes or with the new polisulphone-based Helixone membrane to compare the effects of dialysis technique and membrane type on PS exposure. Removal of PS was assessed indirectly by measuring PS-expressing normal erythrocytes exposed to uraemic plasma or to ultrafiltrate obtained at various time points during the extracorporeal session.
Removal of the uraemic plasma factor(s) causing PS exposure was demonstrated by the reduced ability of uraemic plasma at the end of dialysis to induce PS exposure in normal erythrocytes, and by the capacity of ultrafiltrate from the dialysate side of the dialyzer membrane to markedly increase PS-positive red cells. However, the degree of removal varied according to the dialyzer type and to dialysis technique. Removal was greater for on-line HDF using the Helixone membrane, intermediate and comparable with HD with Helixone and with on-line HDF using standard polysulphone, and lower for HD using polysulphone membrane. The putative uraemic compound causing PS exposure seems to be highly lipophilic, somehow associated with plasma proteins, and apparently having a molecular weight between 10 and 10.8 kDa.
Uraemia is associated with retention of compound(s) that are lipophilic, possibly protein-bound and which cause an abnormal exposure of PS in erythrocytes. Our findings, that such compound(s) can be removed during dialysis and at higher rates with convection techniques, indicate a potential benefit for uraemic patients. The present results also seem to confirm the marked ability of high-flux Helixone membranes to eliminate high molecular weight solutes.
尿毒症期间潴留的溶质会导致红细胞膜外表面的氨基磷脂磷脂酰丝氨酸(PS)暴露增加,这种现象可能通过促进异常的红细胞相互作用而参与尿毒症的病理生理过程。
我们以前瞻性随机交叉方式研究了各种透析方式去除导致红细胞PS外化增加的循环尿毒症因子的能力。每位患者接受血液透析(HD)、使用标准高通量聚砜膜的在线血液透析滤过(HDF)或使用新型基于聚砜的Helixone膜进行治疗,以比较透析技术和膜类型对PS暴露的影响。通过测量暴露于尿毒症血浆或体外循环期间不同时间点获得的超滤液中的表达PS的正常红细胞,间接评估PS的清除情况。
透析结束时尿毒症血浆诱导正常红细胞PS暴露的能力降低,以及透析器膜透析液侧的超滤液使PS阳性红细胞显著增加的能力,证明了导致PS暴露的尿毒症血浆因子被清除。然而,清除程度因透析器类型和透析技术而异。使用Helixone膜的在线HDF清除率更高,中等且与使用Helixone的HD以及使用标准聚砜的在线HDF相当,而使用聚砜膜的HD清除率较低。导致PS暴露的假定尿毒症化合物似乎具有高度亲脂性,以某种方式与血浆蛋白结合,且分子量明显在10至10.8 kDa之间。
尿毒症与亲脂性、可能与蛋白质结合且导致红细胞中PS异常暴露的化合物潴留有关。我们的研究结果表明,此类化合物可在透析期间被清除,且对流技术的清除率更高,这对尿毒症患者具有潜在益处。目前的结果似乎也证实了高通量Helixone膜清除高分子量溶质的显著能力。