Mariano Filippo, Fonsato Valentina, Lanfranco Giacomo, Pohlmeier Robert, Ronco Claudio, Triolo Giorgio, Camussi Giovanni, Tetta Ciro, Passlick-Deetjen Jutta
Department of Medicine Area, Nephrology and Dialysis Unit, CTO Hospital, Turin 10126, Italy.
Nephrol Dial Transplant. 2005 Jun;20(6):1116-26. doi: 10.1093/ndt/gfh776. Epub 2005 Apr 6.
As removal of pro-inflammatory cytokines is limited in conventional diffusive or convective extracorporeal therapies, we studied in two polysulphone membranes with an industrial albumin sieving coefficient of 0.05 (Type A) and 0.13 (Type B) cytokine (IL-6, IL-8, IL-1beta, IL-1ra, TNF-alpha) and plasma protein (albumin, cystatin C, total proteins) permeability profiles. Based on the convective membrane permeability, we evaluated in vitro the dialytic modality that could provide an acceptable balance between high cytokine and low albumin clearances.
Cytokine and plasma protein sieving coefficient (SC) and clearance were studied in (i) post-dilutional haemofiltration mode at 20% fixed ultrafiltration rate; (ii) haemodialysis mode (dialysate flow rate of 3 and 5 l/h); and (iii) haemodiafiltration mode (dialysate flow rate of 3 or 5 l/h with 0.5 l/h of ultrafiltrate).
In haemofiltration mode both Type A and Type B haemodialysers at QB 150 ml/min exhibited similar median SC nearly up to 1 for IL-1beta and IL-1ra, at about 0.6 for IL-6, 0.4 for IL-8 and 0.7 for TNF-alpha, with clearance values ranging from 15 to 30 ml/min. SC were independent of blood flow and were stable throughout the whole experiment. Albumin SC was higher in Type B than in Type A and rapidly decreased from 0.2 to 0.02 and from 0.5 to 0.04 within 3 h for haemodialyser Types A and B, respectively. Cytokine SC was lower in haemodialysis than in haemodiafiltration and haemofiltration mode, and by increasing dialysate flow from 3 up to 5 l/h in both haemodialysis and haemodiafiltration mode, SC for all tested cytokines decreased. However, at 5 l/h clearances were not different or were higher, since increased amounts of dialysate outlet compensated for the decreased SC. Albumin clearances in haemodialysis and haemodiafiltration mode after 360 min at 5 l/h were 0.81 and 0.91 ml/min, respectively.
Our studies show that a mixed convective and diffusive technique ensures high cytokine clearances with an acceptable loss of albumin.
由于在传统的扩散或对流体外治疗中，促炎细胞因子的清除有限，我们研究了两种聚砜膜，其工业白蛋白筛选系数分别为0.05（A型）和0.13（B型），观察细胞因子（白细胞介素-6、白细胞介素-8、白细胞介素-1β、白细胞介素-1受体拮抗剂、肿瘤坏死因子-α）和血浆蛋白（白蛋白、胱抑素C、总蛋白）的通透特性。基于对流膜通透性，我们在体外评估了能在高细胞因子清除率和低白蛋白清除率之间提供可接受平衡的透析方式。
在以下情况下研究细胞因子和血浆蛋白的筛选系数（SC）及清除率：（i）后稀释血液滤过模式，固定超滤率为20%；（ii）血液透析模式（透析液流速为3和5 l/h）；（iii）血液透析滤过模式（透析液流速为3或5 l/h，超滤率为0.5 l/h）。
在血液滤过模式下，QB为150 ml/min时，A型和B型血液透析器对白细胞介素-1β和白细胞介素-1受体拮抗剂的中位SC几乎高达1，白细胞介素-6约为0.6，白细胞介素-8为0.4，肿瘤坏死因子-α为0.7，清除率值在15至30 ml/min之间。SC与血流量无关，且在整个实验过程中保持稳定。B型的白蛋白SC高于A型，A型和B型血液透析器的白蛋白SC分别在3小时内从0.2迅速降至0.02，从从0.5迅速降至0.04。血液透析模式下细胞因子SC低于血液透析滤过和血液滤过模式，在血液透析和血液透析滤过模式中，将透析液流速从3 l/h提高到5 l/h时，所有测试细胞因子的SC均降低。然而，在5 l/h时清除率无差异或更高，因为透析液流出量的增加弥补了SC的降低。在5 l/h下360分钟后，血液透析和血液透析滤过模式下的白蛋白清除率分别为0.81和0.91 ml/min。
我们的研究表明，对流与扩散相结合的技术可确保高细胞因子清除率，同时白蛋白损失可接受。
