心血管疾病相关蛋白结合毒素在高通量血液透析中的清除

目的 探讨终末期肾病患者高通量血液透析对体内心血管疾病相关蛋白结合毒素的清除情况。 方法 选择应用高通量透析器进行维持性血液透析的患者23例。 HPLC-MS-MS（高效液相色谱-串联质谱）法测定透析前后血浆内的对甲酚硫酸盐（PCS）、吲哚硫酸盐（IS）和同型半胱氨酸（Hcy）浓度，计算这些物质的下降率。连续部分透析液收集法收集透析过程中的透析废液，测定透析废液中相应溶质的清除总量（TR）作为血透中溶质清除的金标准。分析这些溶质的清除情况与尿素氮、肌酐清除率及透前溶质血浆水平的关系。 结果 透后PCS、IS和Hcy的总体血浆浓度较透前有所下降，下降率分别为（32.43±11.41）%、（37.38±10.99）%和（57.16±10.43）%，明显低于BUN或Scr的下降率（均P < 0.05），且与BUN和Scr的下降率之间无相关性。游离PCS、IS和Hcy的血浆下降率分别为（55.54±20.75）%、（55.33±19.49）%和（74.63±11.45）%，较总体部分略高（均P < 0.05）。游离PCS和IS的下降率仍不及BUN或Scr的下降率（均P < 0.05）。清除后进入透析废液中的总体和游离PCS的TR分别是（60.58±39.41） mg和（34.87±23.64） mg；总体和游离IS的TR分别为（72.47±45.18） mg和（33.82±24.28） mg；总体和游离Hcy的TR分别为（5.27±3.31） mg和（3.73±1.68） mg。透前血浆PCS、IS和Hcy浓度与清除后进入透析废液中溶质TR均呈正相关（均P < 0.05）。 结论 高通量血液透析可以部分清除心血管疾病相关蛋白结合毒素，其透前血浆浓度与透析清除总量呈正相关，但其清除行为不同于小分子水溶性物质，仍需进一步探索更为有效的蛋白结合毒素的清除方式。

Clearance of protein-bound uremic toxins associated with cardiovascular disease in high-flux hemodialysis

Objective To investigate protein-bound uremic toxins clearance in high-flux hemodialysis patients. Methods Twenty-three high-flux hemodialysis patients from Renji Hospital, Shanghai Jiaotong University School of Medicine were enrolled. Concentrations of p-cresyl sulfate(PCS), indoxylsulfate(IS) and homocysteine(Hcy) were tested by HPLC-MS-MS. Reduction ratios (RRs) and the amount of these toxins in drained dialysate were determined. The relationship of clearance of PCS, IS and Hcy with BUN or Scr was analyzed. Results Plasma levels of the protein-bound toxins were decreased in high-flux hemodialysis. The RRs of total PCS, IS and Hcy were (32.43±11.41)%, (37.38±10.99)% and (57.16±10.43)%，respectively, which were significantly lower than those of BUN or Scr (all P<0.05). Moreover, no correlation was found between the RRs of the total protein-bound compounds and BUN or Scr. The RRs of free PCS, IS and Hcy were (55.54±20.75)%, (55.33±19.49)% and (74.63±11.45)%，respectively. Although RRs of free protein-bound toxins were slightly higher than that of their total, RRs of free PCS and free IS were still inferior to those of BUN or Scr (all P<0.05). Elimination of protein-bound toxins assessed by their mass in dialysate was (60.58±39.41) mg,(34.87±23.64)mg for total and free PCS; (72.47±45.18) mg, (33.82±24.28) mg for total and free IS; (5.27±3.31) mg, (3.73±1.68) mg for total and free Hcy, respectively. The total and free protein-bound uremic toxins mass in dialysate were positively correlated with the pre-treatment plasma concentrations (all P<0.05). Conclusions Protein-bound toxins PCS,IS and Hcy can be partly removed by high-flux hemodialysis, and the elimination of these compounds into dialysate can be predicted by the levels of pre-treatment plasma concentrations. Additionally, the behavior of the protein-bound toxins under study during hemodialysis may be different from water-soluble substances like BUN and Cr. Alternative efficient therapy forms should be explored.